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Introduction: Second language learning is a multifaceted task that benefits across numerous neurocognitive domains including central auditory processing. Existing cross-sectional and longitudinal data show that performance on tests of central auditory processing [central auditory tests (CATs)] worsens with HIV infection. Second language learning may modify this relationship. To explore the relationship between second language learning, central auditory processing, and its interaction with HIV, we assessed the effect of learning English as a second language on CATs among children both living with and without HIV (CLWH/CLWOH) in Dar es Salaam, Tanzania. Methods: Three hundred and seventy-two native Kiswahili speaking children aged 3-10 years old (196 CLWOH, 176 CLWH) were enrolled. Participants completed questionnaires about English language learning, socioeconomic status (SES), and health history. Three central auditory tests-the Triple Digit Test (TDT), the Staggered Spondaic Word Test (SSW), and the Hearing-In-Noise Test (HINT)-were used to assess each participant's central auditory processing abilities. Multivariate linear regression was used to assess the effect of written and spoken English language learning at home and in school on CATs with age, HIV-status, and SES included in each model. Results: HIV status, age, and SES were all significant predictors of all three central auditory tests, with CLWH performing significantly worse on all three CATs than CLWOH. Children actively learning spoken and written English at home had significantly better central auditory processing abilities on the TDT compared to children not actively learning English at home (p < 0.01) independent of HIV status, age, and SES. Children learning spoken and written English at school performed significantly better on the HINT (p < 0.05) than those not actively learning English at school. Discussion: Learning English at home and learning English in school were associated with improved central auditory performance independent of HIV status, SES, and age. These findings also underscore the significance of second language acquisition as a potential mechanism of improving central auditory function within a Kiswahili-speaking cohort. This study found differences in central auditory processing between children exposed to English at home and in school, suggesting differences in language learning in both settings mediated by SES, and this benefit exists regardless of HIV status. [ABSTRACT FROM AUTHOR]

Importance: Predicting neurocognitive deficits using complex auditory assessments could change how cognitive dysfunction is identified, and monitored over time. Detecting cognitive impairment in people living with HIV (PLWH) is important for early intervention, especially in low- to middle-income countries where most cases exist. Auditory tests relate to neurocognitive test results, but the incremental predictive capability beyond demographic factors is unknown. Objective: Use machine learning to predict neurocognitive deficits, using auditory tests and demographic factors. Setting: The Infectious Disease Center in Dar es Salaam, Tanzania Participants: Participants were 939 Tanzanian individuals from Dar es Salaam living with and without HIV who were part of a longitudinal study. Patients who had only one visit, a positive history of ear drainage, concussion, significant noise or chemical exposure, neurological disease, mental illness, or exposure to ototoxic antibiotics (e.g., gentamycin), or chemotherapy were excluded. This provided 478 participants (349 PLWH, 129 HIV-negative). Participant data were randomized to training and test sets for machine learning. Main outcome(s) and measure(s): The main outcome was whether auditory variables combined with relevant demographic variables could predict neurocognitive dysfunction (defined as a score of <26 on the Kiswahili Montreal Cognitive Assessment) better than demographic factors alone. The performance of predictive machine learning algorithms was primarily evaluated using the area under the receiver operational characteristic curve. Secondary metrics for evaluation included F1 scores, accuracies, and the Youden's indices for the algorithms. Results: The percentage of individuals with cognitive deficits was 36.2% (139 PLWH and 34 HIV-negative). The Gaussian and kernel naïve Bayes classifiers were the most predictive algorithms for neurocognitive impairment. Algorithms trained with auditory variables had average area under the curve values of 0.91 and 0.87, F1 scores (metric for precision and recall) of 0.81 and 0.76, and average accuracies of 86.3% and 81.9% respectively. Algorithms trained without auditory variables as features were statistically worse (p <.001) in both the primary measure of area under the curve (0.82/0.78) and the secondary measure of accuracy (72.3%/74.5%) for the Gaussian and kernel algorithms respectively. Conclusions and relevance: Auditory variables improved the prediction of cognitive function. Since auditory tests are easy-to-administer and often naturalistic tasks, they may offer objective measures or predictors of neurocognitive performance suitable for many global settings. Further research and development into using machine learning algorithms for predicting cognitive outcomes should be pursued. [ABSTRACT FROM AUTHOR]

BackgroundInternet-based programs can help provide accessible and inexpensive behavioral health care to those in need; however, the evaluation of these interventions has been mostly limited to controlled trials. Data regarding patterns of use and effectiveness of self-referred, open-access online interventions are lacking. We evaluated an online-based treatment designed to address stress, depression, and conflict management, the Dartmouth PATH Program, in a freely available and self-guided format during the COVID-19 pandemic. ObjectiveThe primary aim is to determine users’ levels of stress and depression, and the nature of problems and triggers they reported during the COVID-19 pandemic. A secondary objective is to assess the acceptability and usability of the PATH content and determine whether such a program would be useful as a stand-alone open-access resource. The final objective is understanding the high dropout rates associated with online behavioral programs by contrasting the use pattern and program efficacy of individuals who completed session one and did not return to the program with those who came back to complete more sessions. MethodsCumulative anonymous data from 562 individuals were analyzed. Stress triggers, stress responses, and reported problems were analyzed using qualitative analysis techniques. Scores on usability and acceptability questionnaires were evaluated using the sign test and Wilcoxon signed rank test. Mixed-effects linear modeling was used to evaluate changes in stress and depression over time. ResultsA total of 2484 users registered from April through October 2020, most of whom created an account without initiating a module. A total of 562 individuals started the program and were considered in the data analysis. The most common stress triggers individuals reported involved either conflicts with family or spouses and work or workload. The most common problems addressed in the mood module were worry, anxiousness, or stress and difficulty concentrating or procrastination. The attrition rate was high with 13% (21/156) completing the conflict module, 17% (50/289) completing session one of the mood module, and 14% (16/117) completing session one of the stress module. Usability and acceptability scores for the mood and stress modules were significantly better than average. In those who returned to complete sessions, symptoms of stress showed a significant improvement over time (P=.03), and there was a significant decrease in depressive symptoms over all time points (P=.01). Depression severity decreased on average by 20% (SD 35.2%; P=.60) between sessions one and two. ConclusionsConflicts with others, worry, and difficulty concentrating were some of the most common problems people used the programs to address. Individuals who completed the modules indicated improvements in self-reported stress and depression symptoms. Users also found the modules to be effective and rated the program highly for usability and acceptability. Nevertheless, the attrition rate was very high, as has been found with other freely available online-based interventions. Trial RegistrationClinicalTrials.gov NCT02726061; https://clinicaltrials.gov/ct2/show/NCT02726061

BackgroundHyperbaric oxygen (HBO2)—oxygen at pressures higher than atmospheric—is approved for 14 indications by the Undersea and Hyperbaric Medical Society. HBO2’s main effect is to increase oxygen content in plasma and body tissues, which can counteract hypoxia or ischemia. Laboratory studies show that HBO2 has effects beyond relieving hypoxia (eg, promoting angiogenesis in irradiated tissue, anti-inflammatory effects, radiosensitization of tumors, hypoxia preconditioning, and fungal growth inhibition) and has potential to treat conditions such as inflammatory bowel disease and pyoderma gangrenosum. Lack of consistently collected outcome data on a large cohort of individuals receiving HBO2 therapy limits its use for both established and new indications. A course of therapy often involves 30-40 visits to a hyperbaric chamber, so the number of patients seen at any given center is constrained by chamber capacity. As a result, published HBO2 outcome data tend to be from small case series because few patients with a particular condition are treated at a given center. To solve this problem, a registry that collects and pools data systematically from multiple institutions has been established. ObjectiveThe aim of this study is to collect consistent outcome data across multiple hyperbaric centers to assess treatment effectiveness and establish a research consortium. MethodsA consortium of hyperbaric centers who have agreed to collect consistent outcome data on all patients seen has been assembled. Data are collected at each participating center using Research Electronic Data Capture (REDCap), a web-based, data collection system used frequently for research. Standard outcome measures have been defined for each condition, which are programmed into the REDCap data collection templates. Governance is through a consortium agreement that defines data security, data sharing, publications, liability, and other issues. Centers obtain Institutional Review Board (IRB) and ethics approval to participate, either from their own institutions or by relying on the IRB at the coordinating center at Dartmouth College. Dissemination will occur through a yearly report and by publications based on the data in the registry. ResultsEarly results from some common indications show significant pretreatment to posttreatment changes. Additional indications and outcome measures are being added using the procedures outlined in the consortium agreement. ConclusionsThe registry collects consistent outcome information for a therapy that needs further study and a stronger evidence base. It also overcomes the challenge of collecting data from an adequate number of patients for both established and emerging indications by combining data collection from multiple centers. The data entry requirements should be within the capabilities of existing staff at any given hyperbaric center. By using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements. Through the registry, a network of enrolled hyperbaric centers has been established that provides the basis for a clinical trial network. International Registered Report Identifier (IRRID)DERR1-10.2196/18857

This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. Cross-sectional. 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH. [ABSTRACT FROM AUTHOR]

Blood levels of histamine and serotonin (5-HT) are altered in human malaria, and, at these levels, we have shown they have broad, independent effects on Anopheles stephensi following ingestion by this invasive mosquito. Given that histamine and 5-HT are ingested together under natural conditions and that histaminergic and serotonergic signaling are networked in other organisms, we examined effects of combinations of these biogenic amines provisioned to A. stephensi at healthy human levels (high 5-HT, low histamine) or levels associated with severe malaria (low 5-HT, high histamine). Treatments were delivered in water (priming) before feeding A. stephensi on Plasmodium yoelii-infected mice or via artificial blood meal. Relative to effects of histamine and 5-HT alone, effects of biogenic amine combinations were complex. Biogenic amine treatments had the greatest impact on the first oviposition cycle, with high histamine moderating low 5-HT effects in combination. In contrast, clutch sizes were similar across combination and individual treatments. While high histamine alone increased uninfected A. stephensi weekly lifetime blood feeding, neither combination altered this tendency relative to controls. The tendency to re-feed 2 weeks after the first blood meal was altered by combination treatments, but this depended on mode of delivery. For blood delivery, malaria-associated treatments yielded higher percentages of fed females relative to healthy-associated treatments, but the converse was true for priming. Female mosquitoes treated with the malaria-associated combination exhibited enhanced flight behavior and object inspection relative to controls and healthy combination treatment. Mosquitoes primed with the malaria-associated combination exhibited higher mean oocysts and sporozoite infection prevalence relative to the healthy combination, with high histamine having a dominant effect on these patterns. Compared with uninfected A. stephensi, the tendency of infected mosquitoes to take a second blood meal revealed an interaction of biogenic amines with infection. We used a mathematical model to project the impacts of different levels of biogenic amines and associated changes on outbreaks in human populations. While not all outbreak parameters were impacted the same, the sum of effects suggests that histamine and 5-HT alter the likelihood of transmission by mosquitoes that feed on hosts with symptomatic malaria versus a healthy host. [ABSTRACT FROM AUTHOR]

This study's objective was determining whether gap detection deficits are present in a longstanding cohort of people living with HIV (PLWH) compared to those living without HIV (PLWOH) using a new gap detection modelling technique (i.e. fitting gap responses using the Hill equation and analysing the individual gap detection resulting curves with non-linear statistics). This approach provides a measure of both gap threshold and the steepness of the gap length/correct detection relationship. The relationship between the correct identification rate at each gap length was modelled using the Hill equation. Results were analysed using a nonlinear mixed-effect regression model. 45 PLWH (age range 41–78) and 39 PLWOH (age range 38–79) were enrolled and completed gap detection testing. The likelihood ratio statistic comparing the full regression model with the HIV effects to the null model, assuming one population curve for both groups, was highly significant (p < 0.001), suggesting a less precise relationship between gap length and correct detection in PLWH. PLWH showed degraded gap detection ability compared to PLWOH, likely due to central nervous system effects of HIV infection or treatment. The Hill equation provided a new approach for modelling gap detection ability. [ABSTRACT FROM AUTHOR]

Although a causal relationship exists between military occupational noise exposure and hearing loss, researchers have struggled to identify and/or characterize specific operational noise exposures that produce measurable changes in hearing function shortly following an exposure. Growing evidence suggests that current standards for noise-exposure limits are not good predictors of true hearing damage. In this study, the aim was to capture the dose-response relationship during military rifle training exercises for noise exposure and hearing threshold. To capture exposure, a wearable system capable of measuring impulse noise simultaneously on-body and in-ear, behind hearing protection was used. To characterize hearing threshold changes, portable audiometry was employed within 2 h before and after exposure. The median 8-h time-weighted, protected, free-field equivalent in-ear exposure was 87.5 dBA at one site and 80.7 dBA at a second site. A significant dose-response correlation between in-ear noise exposure and postexposure hearing threshold changes across our population (R = 0.40 , p = 0.0281) was observed. The results demonstrate an approach for establishing damage risk criteria (DRC) for in-ear, protected measurements based on hearing threshold changes. While an in-ear DRC does not currently exist, it may be critical for predicting the risk of injury for noise environments where protection is mandatory and fit status can vary. [ABSTRACT FROM AUTHOR]

Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive. [ABSTRACT FROM AUTHOR]

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV– controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models. Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests. Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders. [ABSTRACT FROM AUTHOR]

Distortion product otoacoustic emission (DPOAE) mapping characterises cochlear function, can include both the 2f1-2f2 and 2f2-2f1 DPOAEs, and shows promise for tracking cochlear changes. DPOAE amplitude measurements are not as repeatable longitudinally as pure-tone audiometry, likely due in part to probe placement sensitivity. We hypothesised that DPOAE level map variation over multiple testing sessions could be minimised by replacing traditional rubber tips with custom-moulded probe tips. Traditional rubber tips (TRT) and custom-moulded probes tips (CMPT) were used to measure DPOAE level maps repeatedly over five sessions. Probe placement was assessed using a frequency sweep in the ear canal. Repeatability of the DPOAE level maps was assessed using a Bland-Altman analysis. Overall map repeatability was assessed by measuring differences in distortion product amplitude over sessions. Crossover study with a convenience sample size of six adults. The CMPT frequency sweeps showed reduced variability in probe placement. The repeatability coefficient for individual DPOAEs measurements improved from 6.9 dB SPL with the TRT to 5.1 dB SPL with the CMPT. Map repeatability improved for most subjects with the CMPT. [ABSTRACT FROM AUTHOR]

Internal jugular flow is reduced in space compared with supine values, which can be associated with internal jugular vein (IJV) thrombosis. The mechanism is unknown but important to understand to prevent potentially serious vein thromboses on long duration flights. We used a novel, microgravity‐focused numerical model of the cranial vascular circulation to develop hypotheses for the reduced flow. This model includes the effects of removing hydrostatic gradients and tissue compressive forces – unique effects of weightlessness. The IJV in the model incorporates sensitivity to transmural pressure across the vein, which can dramatically affect resistance and flow in the vein. The model predicts reduced IJV flow in space. Although tissue weight in the neck is reduced in weightlessness, increasing transmural pressure, this is more than offset by the reduction in venous pressure produced by the loss of hydrostatic gradients and tissue pressures throughout the body. This results in a negative transmural pressure and increased IJV resistance. Unlike the IJV, the walls of the vertebral plexus are rigid; transmural pressure does not affect its resistance and so its flow increases in microgravity. This overall result is supported by spaceflight measurements, showing reduced IJV area inflight compared with supine values preflight. Significantly, this hypothesis suggests that interventions that further decrease internal IJV pressure (such as lower body negative pressure), which are not assisted by other drainage mechanisms (e.g. gravity), might lead to stagnant flow or IJV collapse with reduced flow, which could increase rather than decrease the risk of venous thrombosis. [ABSTRACT FROM AUTHOR]

The article presents the discussion on spaceflight-associated neuro-ocular syndrome (SANS) occuring in some long-duration astronauts. Topics include combining with the distended appearance of jugular veins in space leading to the hypothesis about intracranial pressure (ICP); and removal of the forces explaining the paradoxical CVP results showing a reduction in CVP below supine levels combining with an increase in stroke volume.

Purpose: Previous studies have revealed increased frontal brain activation during speech comprehension in background noise. Few, however, used tonal languages. The normal pattern of brain activation during a challenging speech-in-nose task using a tonal language remains unclear. The Mandarin Hearing-in-Noise Test (HINT) is a well-established test for assessing the ability to interpret speech in background noise. The current study used Mandarin HINT (MHINT) sentences and functional magnetic resonance imaging (fMRI) to assess brain activation with MHINT sentences. Methods: Thirty native Mandarin-speaking subjects with normal peripheral hearing were recruited. Functional MRI was performed while subjects were presented with either HINT "clear" sentences with low-level background noise [signal-to-noise ratio (SNR) = +3 dB] or "noisy" sentences with high-level background noise (SNR = −5 dB). Subjects were instructed to answer with a button press whether a visually presented target word was included in the sentence. Brain activation between noisy and clear sentences was compared. Activation in each condition was also compared to a resting, no sentence presentation, condition. Results: Noisy sentence comprehension showed increased activity in areas associated with tone processing and working memory, including the right superior and middle frontal gyri [Brodmann Areas (BAs) 46, 10]. Reduced activity with noisy sentences was seen in auditory, language, memory and somatosensory areas, including the bilateral superior and middle temporal gyri, left Heschl's gyrus (BAs 21, 22), right temporal pole (BA 38), bilateral amygdala-hippocampus junction, and parahippocampal gyrus (BAs 28, 35), left inferior parietal lobule extending to left postcentral gyrus (BAs 2, 40), and left putamen. Conclusion: Increased frontal activation in the right hemisphere occurred when comprehending noisy spoken sentences in Mandarin. Compared to studies using non-tonal languages, this activation was strongly right-sided and involved subregions not previously reported. These findings may reflect additional effort in lexical tone perception in this tonal language. Additionally, this continuous fMRI protocol may offer a time-efficient way to assess group differences in brain activation with a challenging speech-in-noise task. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Isolated and confined environments (ICEs), such as spaceflight, are challenging psychologically. We have been evaluating self-directed tools to sustain and improve psychological well-being in these settings. The Expedition Application for Peak Psychological Performance (Expedition-APPP) is an interactive media-based set of self-directed tools that address conflict resolution, stress management, and depression treatment. Virtual reality (VR) of nature scenes is a tool to improve attention and relieve stress by providing users with an immersive nature experience. We evaluated both Expedition-APPP and VR in an ICE. METHODS: The Expedition-APP was evaluated during three, and nature VR during two, deployments at the HI-SEAS habitat, where crews of six were isolated for 8–12 mo. Participants used both the Expedition-APPP and VR and shared their feedback and experiences after the deployments in semistructured interviews. These interviews were evaluated using qualitative analysis techniques to gather generalizable insights into implementing autonomous mental health programs for people living and working in ICEs. RESULTS: Expedition-APPP modules provided a shared culture, language, and tools for working through challenges. VR allowed for access to emotions and experiences that were unavailable in the habitat. Suggestions for improvement included making refresher training easily available and providing a wider range of content to address different individuals’ coping styles. DISCUSSION: Both the Expedition-APPP and VR were appreciated and used, although a wider range of content and experiences was desired by participants. [ABSTRACT FROM AUTHOR]

On Earth, tissue weight generates compressive forces that press on body structures and act on the walls of vessels throughout the body. In microgravity, tissues no longer have weight, and tissue compressive forces are lost, suggesting that individuals who weigh more may show greater effects from microgravity exposure. One unique effect of long-duration microgravity exposure is spaceflight-associated neuroocular syndrome (SANS), which can present with globe flattening, choroidal folds, optic disk edema, and a hyperopic visual shift. To determine whether weight or other anthropometric measures are related to ocular changes in space, we analyzed data from 45 individual long-duration astronauts (mean age 47, 36 male, 9 female, mean mission duration 165 days) who had pre- and postflight measures of disk edema, choroidal folds, and manifest ocular refraction. The mean preflight weights of astronauts who developed new choroidal folds [78.6 kg with no new folds vs. 88.6 kg with new folds (F = 6.2, P = 0.02)] and disk edema [79.1 kg with no edema vs. 95 kg with edema (F = 9.6, P = 0.003)] were significantly greater than those who did not. Chest and waist circumferences were also significantly greater in those who developed folds or edema. The odds of developing disk edema or new choroidal folds were 55% in the highest- and 9% in the lowest-weight quartile. In this cohort, no women developed disk edema or choroidal folds, although women also weighed significantly less than men [62.9 vs. 85.2 kg (F = 53.2, P < 0.0001)]. Preflight body weight and anthropometric factors may predict microgravity-induced ocular changes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We evaluated the reproducibility of two portable, self-administered autorefractors (Netra and SVOne Pro) to assess the time course of visual changes on the ISS. METHODS: We measured cycloplegic refractive error at 5 visits at least a week apart in 13 subjects (6 women, 7 men, 30 ± 9 yr) using both devices seated and also prone with lower body positive pressure (LBPP) applied. Axial length was measured with an optical biometer. Subjects completed a questionnaire on device preferences. RESULTS: The SVOne seated intrasession reproducibility coefficient (RPC) was 0.37 diopters (D), while the Netra's was 0.41 D. Intersession seated results were: RPC = 0.67 D for the SVOne and RPC = 0.54 D for the Netra. The average seated to prone LBPP differences were significantly different from zero for both the SVOne and Netra. The SVOne was preferred in four out of five categories on the questionnaire and took half the time to complete a measurement set compared to the Netra. DISCUSSION: Users preferred the SVOne and it took less time. An SVOne refraction change of 0.67 D from baseline would happen by chance less than 5% of the time. If multiple separate measurements were taken, the detection limit could be reduced (e.g., three repeated measurements could reduce it to 0.38 D). Since astronauts with visual changes show spherical equivalent changes of 0.5 to 1.0 D, in-flight autorefractors could help determine the time course of refractive changes in space from which changes in axial length could be inferred. [ABSTRACT FROM AUTHOR]

Some astronauts are returning from long-duration spaceflight with structural ocular and visual changes. We investigated both the transient and sustained effects of changes in the direction of the gravity vector acting on the eye using changes in body posture. Intraocular pressure (IOP; measured by Perkins tonometer), ocular geometry (axial length, corneal thickness, and aqueous depth-noncontact biometer), and the choroid (volume and subfoveal thickness optical coherence tomography) were measured in 10 subjects (5 males and 5 females). Measures were taken over the course of 60 min and analyzed with repeated-measures analysis of covariance to assess the effects of posture and time. In the supine position, choroidal volume increased significantly with time (average value at <5 min = 8.8 ± 2.3 mm3, 60 min = 9.0 ± 2.4 mm3, P = 0.03). In the prone position, IOP and axial length increased with time (IOP at <5 min 15 ± 2.7 mmHg, 60 min = 19.8 ± 4.1 mmHg, P < 0.0001; axial length at <5 min = 24.29 ± 0.77 mm, 60 min = 24.31 ± 0.76 mm, P = 0.002). Each increased exponentially, with time constants of 5.3 and 14 min, respectively. Prone corneal thickness also increased with time (<5 min = 528 ± 35 μm, 60 min = 537 ± 35 μm3, P < 0.001). Aqueous depth was shortened in the prone position (baseline = 3.22 ± 0.31 mm, 60 min = 3.18 ± 0.32 mm, P < 0.0001) but did not change with time. The data show that changes in the gravity vector have pronounced transient and sustained effects on the geometry and physiology of the eye. NEW & NOTEWORTHY We show that gravity has pronounced transient and sustained effects on the eye by making detailed ocular measurements over 60 min in the supine and prone postures. These data inform our understanding of how gravitational forces can affect ocular structures, which is essential for hypothesizing how ocular changes could occur with microgravity exposure. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Virtual reality (VR) can provide exposure to nature for those living in isolated confined environments. We evaluated VR-presented natural settings for reducing stress and improving mood. METHODS: There were 18 participants (9 men, 9 women), ages 32 ± 12 yr, who viewed three 15-min 360° scenes (an indoor control, rural Ireland, and remote beaches). Subjects were mentally stressed with arithmetic before scenes. Electrodermal activity (EDA) and heart rate variability measured psycho-physiological arousal. The Positive and Negative Affect Schedule and the 15-questlon Modified Reality Judgment and Presence Questionnaire (MRJPQ) measured mood and scene quality. RESULTS: Reductions in EDA from baseline were greater at the end of the natural scenes compared to the control scene (-0.59, -0.52, and 0.32 jxS, respectively). The natural scenes reduced negative affect from baseline (Δ = 1.2 and Δ = 1.1 points), but the control scene did not (Δ = 0.4 points). MRJPQ scores for the control scene were lower than both natural scenes (4.9,6.7, and 6.5 points, respectively). Within the two natural scenes, the preferred scene reduced negative affect (Δ = 2.4 points) more than the second choice scene (Δ = 1.8 points) and scored higher on the MRJPQ (6.8 vs. 6.4 points). DISCUSSION: Natural scene VR provided relaxation both objectively and subjectively, and scene preference had a significant effect on mood and perception of scene quality. VR may enable relaxation for people living in isolated confined environments, particularly when matched to personal preferences. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Living in an isolated, confined environment (ICE) can induce conflict, stress, and depression. Computer-based behavioral health countermeasures are appealing for training and treatment in ICEs because they provide confidentiality and do not require communication with the outside environment. We evaluated the Virtual Space Station (VSS), a suite of interactive computer-delivered psychological training and treatment programs, at the Hawaii Space Exploration Analog and Simulation (HI-SEAS) III expedition. METHODS: Six subjects (3 male, 3 female) spent 8 mo in group-isolation and used the Conflict, Stress, and Depression modules in the VSS. Survey evaluations, data collected within the program, and postdeployment interviews were collected. RESULTS: This crew dealt with behavioral health issues common to ICEs. The VSS proved to be a valuable resource and was used both as intended, and in unanticipated ways, to help maintain behavioral health. The Conflict and Stress Modules were rated as highly acceptable (1.8 on a 7-point Likert scale). The crew identified a total of 13 stressors and worked on 9 problems through the VSS. Opinions about the modules were highly individualized. Crewmembers identified exercises in the VSS that were applicable and not applicable to their needs. Additional content to improve the program was identified. DISCUSSION: Autonomous, confidential training and treatment for behavioral health issues will need to be a critical component of long duration spaceflight travel. This work provides an evaluation of such a tool in a relevant ICE. [ABSTRACT FROM AUTHOR]

Intraocular pressure (IOP) initially increases when an individual enters microgravity compared with baseline values when an individual is in a seated position. This has been attributed to a headward fluid shift that increases venous pressures in the head. The change in IOP exceeds changes measured immediately after moving from seated to supine postures on Earth, when a similar fluid shift is produced. Furthermore, central venous and cerebrospinal fluid pressures are at or below supine position levels when measured initially upon entering microgravity, unlike when moving from seated to supine postures on Earth, when these pressures increase. To investigate the effects of altering gravitational forces on the eye, we made ocular measurements on 24 subjects (13 men, 11 women) in the seated, supine, and prone positions in the laboratory, and upon entering microgravity during parabolic flight. IOP in microgravity (16.3 ± 2.7 mmHg) was significantly elevated above values in the seated (11.5 ± 2.0 mmHg) and supine (13.7 ± 3.0 mmHg) positions, and was significantly less than pressure in the prone position (20.3 ± 2.6 mmHg). In all measurements, P < 0.001. Choroidal area was significantly increased in subjects in a microgravity environment (P < 0.007) compared with values from subjects in seated (increase of 0.09 ± 0.1 mm2) and supine (increase of 0.06 ± 0.09 mm2) positions. IOP results are consistent with the hypothesis that hydrostatic gradients affect IOP, and may explain how IOP can increase beyond supine values in microgravity when central venous and intracranial pressure do not. Understanding gravitational effects on the eye may help develop hypotheses for how microgravityinduced visual changes develop. [ABSTRACT FROM AUTHOR]

Distortion product otoacoustic emission (DPOAE) level mapping provides a comprehensive picture of cochlear responses over a range of DP frequencies and f2/f1 ratios. We hypothesized that individuals exposed to high-level sound would show changes detectable by DPOAE mapping, but not apparent on a standard DP-gram. Thirteen normal hearing subjects were studied before and after attending music concerts. Pure-tone audiometry (500-8,000 Hz), DP-grams (0.3-10 kHz) at 1.22 ratio, and DPOAE level maps were collected prior to, as soon as possible after, and the day after the concerts. All maps covered the range of 2,000-6,000 Hz in DP frequency and from 1.3 to -1.3 in ratio using equi-level primary tone stimuli. Changes in the pure-tone audiogram were significant (P ≤ 0.01) immediately after the concert at 1,000 Hz, 4,000 Hz, and 6,000 Hz. The DPgram showed significant differences only at f2 = 4,066 (P = 0.01) and f2 = 4,348 (P = 0.04). The postconcert changes were readily apparent both visually and statistically (P ≤ 0.01) on the mean DP level maps, and remained statistically significantly different from baseline the day after noise exposure although no significant changes from baseline were seen on the DP-gram or audiogram the day after exposure. Although both the DP-gram and audiogram showed recovery by the next day, the average DPOAE level maps remained significantly different from baseline. The mapping data showed changes in the cochlea that were not detected from the DP-gram obtained at a single ratio. DPOAE level mapping provides comprehensive information on subtle cochlear responses, which may offer advantages for studying and tracking noise-induced hearing loss (NIHL). [ABSTRACT FROM AUTHOR]

Objective: Our objective was to obtain reliable threshold measurements without a sound booth by using a passive noise-attenuating hearing protector combined with in-ear 1/3-octave band noise measurements to verify the ear canal was suitably quiet. Design: We deployed laptop-based hearing testing systems to Tanzania as part of a study of HIV infection and hearing. An in-ear probe containing a microphone was used under the hearing protector for both the in-ear noise measurements and threshold audiometry. The 1/3-octave band noise spectrum from the microphone was displayed on the operator's screen with acceptable levels in grey and unacceptable levels in red. Operators attempted to make all bars grey, but focused on achieving grey bars at 2000 Hz and above. Study sample: 624 adults and 197 children provided 3381 in-ear octave band measurements. Repeated measurements from 144 individuals who returned for testing on three separate occasions were also analysed. Results: In-ear noise levels exceeded the maximum permissible ambient noise levels (MPANL) for ears not covered, but not the dB SPL levels corresponding to 0 dB HL between 2000-4000 Hz. In-ear noise measurements were repeatable over time. Conclusions: Reliable audiometry can be performed using a passive noise-attenuating hearing protector and in-ear noise measurements. [ABSTRACT FROM AUTHOR]

The updated funding statement therefore reads: This work was supported by the National Institutes of Health grant from the National Institute of Neurological Disorders and Stroke (R01NS108809) and the Shanghai Municipal Commission of Health and Family Planning (No. 201840146). Keywords: central auditory processing; functional MRI; frontal lobe; tonal language; hearing-in-noise test EN central auditory processing functional MRI frontal lobe tonal language hearing-in-noise test N.PAG N.PAG 1 05/17/21 20210512 NES 210512 In the original article, we neglected to include the funder Shanghai Municipal Commission of Health and Family Planning, No. 201840146 to YS. Central auditory processing, functional MRI, frontal lobe, tonal language, hearing-in-noise test. [Extracted from the article]

Our previous work demonstrated that basophils regulate a suite of malaria phenotypes, including intestinal mastocytosis and permeability, the immune response to infection, gametocytemia, and parasite transmission to the malaria mosquito Anopheles stephensi. Given that activated basophils are primary sources of the regulatory cytokines IL-4 and IL-13, we sought to examine the contributions of these mediators to basophil-dependent phenotypes in malaria. We generated mice with basophils depleted for IL-4 and IL-13 (baso IL-4/IL-13 (-)) and genotype controls (baso IL-4/IL-13 (+)) by crossing mcpt8-Cre and Il4/Il13fl/fl mice and infected them with Plasmodium yoelii yoelii 17XNL. Conditional deletion was associated with ileal mastocytosis and mast cell (MC) activation, increased intestinal permeability, and increased bacterial 16S levels in blood, but it had no effect on neutrophil activation, parasitemia, or transmission to A. stephensi. Increased intestinal permeability in baso IL-4/IL-13 (-) mice was correlated with elevated plasma eotaxin (CCL11), a potent eosinophil chemoattractant, and increased ileal MCs, proinflammatory IL-17A, and the chemokines MIP-1α (CCL3) and MIP-1β (CCL4). Blood bacterial 16S copies were positively but weakly correlated with plasma proinflammatory cytokines IFN-γ and IL-12p40, suggesting that baso IL-4/IL-13 (-) mice failed to control bacterial translocation into the blood during malaria infection. These observations suggest that basophil-derived IL-4 and IL-13 do not contribute to basophil-dependent regulation of parasite transmission, but these cytokines do orchestrate protection of intestinal barrier integrity after P. yoelii infection. Specifically, basophil-dependent IL-4/IL-13 control MC activation and prevent infection-induced intestinal barrier damage and bacteremia, perhaps via regulation of eosinophils, macrophages, and Th17-mediated inflammation., (Copyright © 2024 The Authors.)

Malaria is strongly predisposed to bacteremia, which is associated with increased gastrointestinal permeability and a poor clinical prognosis. We previously identified mast cells (MCs) as mediators of intestinal permeability in malaria and described multiple cytokines that rise with parasitemia, including interleukin (IL)-10, which could protect the host from an inflammatory response and alter parasite transmission to Anopheles mosquitoes. Here, we used the Cre-loxP system and non-lethal Plasmodium yoelii yoelii 17XNL to study the roles of MC-derived IL-10 in malaria immunity and transmission. Our data suggest a sex-biased and local inflammatory response mediated by MC-derived IL-10, supported by early increased number and activation of MCs in females relative to males. Increased parasitemia in female MC IL-10 (-) mice was associated with increased ileal levels of chemokines and plasma myeloperoxidase (MPO). We also observed increased intestinal permeability in female and male MC IL-10 (-) mice relative to MC IL-10 (+) mice but no differences in blood bacterial 16S DNA levels. Transmission success of P. yoelii to A. stephensi was higher in female relative to male mice and from female and male MC IL-10 (-) mice relative to MC IL-10 (+) mice. These patterns were associated with increased plasma levels of pro-inflammatory cytokines in female MC IL-10 (-) mice and increased plasma levels of chemokines and markers of neutrophil activation in male MC IL-10 (-) mice. Overall, these data suggest that MC-derived IL-10 protects intestinal barrier integrity, regulates parasite transmission, and controls local and systemic host immune responses during malaria, with a female bias., Competing Interests: The authors declare no conflict of interest.

Background: Effective negotiation in relationships is critical for successful long-duration space missions; inadequate conflict resolution has shown serious consequences. Less desirable forms of negotiation, including positional bargaining (eg, negotiating prices), can exacerbate conflicts. Traditional positional bargaining may work for simple, low-stakes transactions but does not prioritize ongoing relationships. High-stakes situations warrant interest-based negotiation, where parties with competing interests or goals collaborate in a mutually beneficial agreement. This is learnable but must be practiced. Refresher training during conflicts is important to prevent out-of-practice crew members from using less effective negotiation techniques. Training should be self-directed and not involve others because, on a space mission, the only other people available may be part of the conflict., Objective: We aimed to develop and test an interactive module teaching principles and skills of interest-based negotiation in a way that users find acceptable, valuable for learning, and enjoyable., Methods: Using a web-based, interactive-media approach, we scripted, filmed, and programmed an interest-based negotiation interactive training module. In the module, the program mentor introduces users to "The Circle of Value" approach to negotiation and highlights its key concepts through interactive scenarios requiring users to make selections at specific decision points. Each selection prompts feedback designed to reinforce a teaching point or highlight a particular negotiation technique. To evaluate the module, we sought populations experiencing isolation and confinement (an opportunistic design). This included 9 participants in isolated, confined environments in the Australian Antarctic Program and the Hawai'i Space Exploration Analog and Simulation Mars simulation, as well as a subset of people who self-identified as being isolated and confined during the COVID-19 pandemic. Feedback was collected from participants (n=54) through free-response answers and questionnaires with numerical scaling (0=strongly disagree to 4=strongly agree) at the end of the module., Results: In total, 51 of 54 (94%) participants found the activity valuable for learning about conflict management (identified by those who selected either "somewhat agree" or "strongly agree"), including 100% of participants in the isolated and confined environment subset (mode=3). In total, 79% (128/162) of participant responses indicated that the module was realistic (mode=3), including 85% (23/27) of responses from participants in isolated and confined environments (mode=3). Most participants felt that this would be particularly valuable for new team members in an isolated, confined environment (46/54, 85% of all participants, mode 4; 7/9, 78% of the isolated and confined environment subset, mode 3) as well as veterans., Conclusions: This module offers a self-directed, consistent approach to interest-based negotiation training, which is well received by users. Although the data are limited due to the opportunistic study design, the module could be useful for individuals in isolated and confined environments and for anyone involved in high-stakes negotiations where sustaining relationships is essential., (©Jennifer Fleischer, Jeff Ayton, Maree Riley, Kim Binsted, Devin R Cowan, Abigail M Fellows, Jeff A Weiss, Jay C Buckey. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.06.2023.)

Background: A unique syndrome affecting young adults of unexplained hearing loss often associated with uncorrectable poor visual acuity and lower extremity numbness is endemic in Dar es Salaam. This study characterized the hearing loss, associated it with other symptoms, and gathered information on potential causes., Methods: Forty-seven patients (23 men, 24 women) <40 years old with a symptom consistent with the syndrome, negative syphilis test, and no head injury history were recruited from Muhimbili National Hospital. 18 controls (10 men, 8 women) were recruited from the same neighborhoods as patients. Hearing ability and cochlear outer hair cell function (distortion-product otoacoustic emissions (DPOAEs)) were assessed, as were visual acuity and color vision. Peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument (MNSI), and physical examination. Blood C-reactive protein levels and toenail trace metal concentrations were measured. Environmental exposures were elicited using a questionnaire. Patients with at least two of the following signs were defined as having the syndrome: poor hearing with normal DPOAEs, vision not correctable to better than 20/30, or a MNSI score greater than 4., Results: 29 participants met the case definition. CRP levels did not differ between groups but manganese, cobalt and tin levels were each greater in the cases than controls. No other environmental exposure differences were noted., Conclusions: Toenail manganese, cobalt, and tin levels were higher in those with the syndrome. These metals are potential neurotoxins suggesting a possible environmental origin for this unique and debilitating syndrome., Competing Interests: Competing Interests The authors have no financial or personal relationships that could inappropriately bias their work.

Objectives: Human immunodeficiency virus positive (HIV+) individuals report hearing difficulties, but standard audiological tests show no, or small, changes in peripheral hearing ability. The hearing complaints may reflect central nervous system (CNS) auditory processing deficits, rather than middle or inner ear problems, and may result from CNS damage due to HIV infection or treatment. If central auditory task performance and cognitive deficits in HIV+ individuals are shown to be related, then central auditory tests might serve as a "window" into CNS function in these patients., Design: We measured cognitive performance (Mandarin Montreal Cognitive Assessment [MoCA]) and speech in noise perception (Mandarin hearing-in-noise test [HINT]) in 166 normal-hearing HIV+ individuals (158 men, 8 women, average age 36 years) at the Shanghai Public Health Clinical Center in Shanghai, China. Data collection included audiometry, tympanometry, and the Amsterdam Inventory of Auditory Handicap (AIAH), which assesses the subjective ability to understand speech and localize sound., Results: Subjects had no middle ear disease and met criteria for normal-hearing sensitivity (all thresholds 20 dB HL or less). A significant negative relationship between speech reception thresholds (SRT) and MoCA scores (r = 0.15, F = 28.2, p < 0.001) existed. Stepwise linear regression showed that when the factors of age, MoCA scores, hearing thresholds, and education level were considered, only age and MoCA scores contributed independently to the SRT results (overall model r = 0.30, F = 38.8, p < 0.001). Subjective hearing complaints from the AIAH supported the HINT results. AIAH and MoCA scores were also related (r = 0.05, F = 8.5, p = 0.004), with those with worse MoCA scores having more problems on the AIAH. When the cohort was divided into those with normal and abnormal performance on the MoCA, those with abnormal performance on the MoCA had significantly higher average SRTs (p < 0.001)., Conclusions: Understanding speech in noise measured both objectively with the HINT and subjectively with the AIAH was inversely related to cognitive abilities despite a normal ability to hear soft sounds determined by audiometry. Although age was also an important independent factor affecting speech perception, the age relationship within the speech findings in this study may represent more than just age-related declines in speech in noise understanding. Although reliable data on disease duration are not available, the older members of this cohort likely had HIV longer and probably had more severe symptoms at presentation than the younger members because early detection and treatment of HIV in Shanghai has improved over time. Therefore, the age relationship may also include elements of disease duration and severity. Speech perception, especially in challenging listening conditions, involves cortical and subcortical centers and is a demanding neurological task. The problems interpreting speech in noise HIV+ individuals have may reflect HIV-related or HIV treatment-related, central nervous damage, suggesting that CNS complications in HIV+ individuals could potentially be diagnosed and monitored using central auditory tests.

New research suggests that individuals with human immunodeficiency virus (HIV) have central auditory processing deficits. To review the evidence for HIV affecting parts of the central nervous system involved in central auditory processing, we performed a systematic review of the literature. The objective was to determine whether existing studies show evidence for damage to structures associated with central auditory pathways in HIV. We searched PubMed for papers that used structural magnetic resonance imaging (MRI), diffusion tensor imaging, magnetic resonance spectroscopy or functional MRI in individuals infected with HIV. The review showed that HIV affects several areas involved in central auditory processing particularly the thalamus, internal capsule and temporal cortex. These findings support the idea that HIV can affect central auditory pathways and support the potential use of central auditory tests as a way to assess central nervous system effects of HIV.