Basophil-Derived IL-4 and IL-13 Protect Intestinal Barrier Integrity and Control Bacterial Translocation during Malaria.

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-1ß (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.

Machine learning for predicting cognitive deficits using auditory and demographic factors.

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.

Central auditory test performance predicts future neurocognitive function in children living with and without HIV.

Tests of the brain's ability to process complex sounds (central auditory tests) correlate with overall measures of neurocognitive performance. In the low- middle-income countries where resources to conduct detailed cognitive testing is limited, tests that assess the central auditory system may provide a novel and useful way to track neurocognitive performance. This could be particularly useful for children living with HIV (CLWH). To evaluate this, we administered central auditory tests to CLWH and children living without HIV and examined whether central auditory tests given early in a child's life could predict later neurocognitive performance. We used a machine learning technique to incorporate factors known to affect performance on neurocognitive tests, such as education. The results show that central auditory tests are useful predictors of neurocognitive performance and perform as well or in some cases better than factors such as education. Central auditory tests may offer an objective way to track neurocognitive performance in CLWH.

Mast cell-derived IL-10 protects intestinal barrier integrity during malaria in mice and regulates parasite transmission to Anopheles stephensi with a female-biased immune response.

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.

A Central Auditory Test reveals differences between drug treatment regimens in adults living with HIV.

OBJECTIVE: 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. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Ingested histamine and serotonin interact to alter Anopheles stephensi feeding and flight behavior and infection with Plasmodium parasites.

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.

Web-Based, Interactive, Interest-Based Negotiation Training for Managing Conflict in Isolated Environments: Opportunistic Study With an e-Survey.

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.

Preliteracy assessment in children living with HIV in Tanzania: comparison to results from children living without HIV in Tanzania and the United States.

OBJECTIVE: Children with HIV (CWH) are at increased risk for cognitive and developmental delays. Whether HIV affects literacy development, however, remains unknown. Rapid automatized naming (RAN) tasks offer the simplest preliteracy assessment a child can perform that predicts future reading skills across languages. DESIGN AND METHODS: RAN performance was analyzed cross-sectionally on 473 children (249 children without HIV and 217 CWH; ages 3-9) drawn from a longitudinal study in Tanzania. These data were compared to results from 341 normally developing children without HIV (ages 3-8) from the United States. Participants performed two RAN subtests: colors and objects. RESULTS: RAN object completion was greater than for the RAN color in Tanzanian children. CWH were less likely to complete either subtest and performed worse on the object subtest compared to Tanzanian children without HIV. Compared to the US cohort, the Tanzanian cohort was less likely to complete both subtests - in particular the colors subtest - and showed more variability in responses at younger ages. After approximately age 6, however, the trajectory of improvement between the United States and Tanzania was similar. CONCLUSIONS: CWH performed worse on this per-literacy test, indicating literacy skill development in CWH needs further study. The differences between US and Tanzanian results likely reflect variability in when children learn to name colors and objects. The trajectory of improvement between countries became more similar as the children aged. This study motivates further longitudinal analyses aimed at assessing the developmental trajectory of the RAN, its predictive ability for reading skills, and its link with other preliteracy and cognitive skills.

Peripheral Auditory Function in Tanzanian Children Living With HIV With Clinically Normal Hearing.

Importance: Despite normal audiometry, adults living with HIV have lower distortion product otoacoustic emissions (DPOAEs) compared with HIV-negative controls, but the degree of these differences in children living with HIV is unknown. If subclinical auditory deficits are present, results could affect developmental outcomes in children living with HIV (CLWH). Objective: To compare DPOAEs and auditory brainstem responses (ABR) between 2 age- and sex-matched groups of younger children with normal audiometry, 1 infected with HIV and the other uninfected. Design, Setting, and Participants: Cohort study in an infectious disease center in Dar es Salaam, Tanzania. Participants included 340 Tanzanian children aged 3 to 9 years with clinically normal hearing, type A tympanograms bilaterally, and air-conduction thresholds of 20 dB HL or less from 0.5 to 8 kHz. Participants in the cohort repeated testing approximately every 6 months (approximately 2.2 sessions per participant) for a total of 744 total observations. Data were analyzed from March 2020 to January 2022. Main Outcomes and Measures: DPOAE amplitudes from 1.5 to 8 kHz using an f2 to f1 ratio of 1.2 and L1/L2 values of 65/55 dB sound pressure level and click-evoked ABR using a slow (21.1/s) and fast (61.1/s) click rate. Results: A total of 141 CLWH (70 female participants [49.3%]; mean [SD] age, 7.24 [1.67] years) and 199 HIV-negative individuals (99 female participants [49.7%]; mean [SD] age, 7.26 [1.44] years) participated in the study. The groups did not differ significantly in age, static immittance, or air-conduction thresholds. HIV status was independently associated with approximately 1.4 dB (95% CI, -3.28 to 0.30 dB) to 3.8 dB (95% CI, 6.03 to -1.99 dB) lower DPOAE amplitudes at 6 and 8 kHz bilaterally and 0.28 µV (95% CI, 0.01 to 0.33 µV) lower ABR wave V amplitudes in the right ear. Conclusions and Relevance: Consistent with previous findings in young adults, CLWH had slightly, but reliably, lower DPOAEs and ABR wave V amplitudes than HIV-negative controls. The magnitude of these differences was small, but results suggest an early and consistent association between HIV infection or treatment and outer hair cell and auditory brainstem responses in children as young as 3 years. These subclinical changes suggest tracking both auditory function and development outcomes in CLWH is warranted.

Natural Scene Virtual Reality as a Behavioral Health Countermeasure in Isolated, Confined, and Extreme Environments: Three Isolated, Confined, Extreme Analog Case Studies.

INTRODUCTION: Isolated, confined, extreme (ICE) environments are accompanied by a host of stress-inducing circumstances: operational pressure, interpersonal dynamics, limited communication with friends and family, and environmental hazards. We evaluated the effectiveness of attention-restoration-therapy-based immersive Virtual Reality (VR) in three ICE environments: the Canadian Forces Station-Alert (CFS Alert), the 12-month HI-SEAS IV expedition, and the 8-month HI-SEAS V expedition. METHODS: Thirty-one individuals (29 male, 2 female) at CFS Alert, and 12 total crewmembers (7 male, 5 female, six crewmembers per sessions) at HI-SEAS participated. All participants viewed immersive VR scenes, but scene content varied by deployment. Data collection included pre- and post-intervention surveys and semi-structured post-mission interviews. Survey data were analyzed by scene content within each analog using nonparametric approaches. RESULTS: Acceptability and desirability of the VR content varied significantly by ICE analog, as well as by participants within a given analog. The two initial exploratory protocols enabled a more directed study in HI-SEAS V to identify the importance of differences in scene content. DISCUSSION: Use and perceived utility of the VR varied considerably across participants, indicating that psychological support needs to be individualized. Overall, natural scene VR was broadly considered restorative, but after long periods of isolation, dynamic and familiar scenes including those with people were also appealing. Immersive, nature-based VR was highly valued by some, but not all participants, suggesting that this intervention tool holds promise for use in ICE settings but needs to be tailored to the setting and individual.

Gap detection responses modelled using the Hill equation in adults with well-controlled HIV.

OBJECTIVE: 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. DESIGN: 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. STUDY SAMPLE: 45 PLWH (age range 41-78) and 39 PLWOH (age range 38-79) were enrolled and completed gap detection testing. RESULTS: 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. CONCLUSIONS: 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.

Test-Retest repeatability of automated threshold audiometry in Nicaraguan schoolchildren.

OBJECTIVE: Automated threshold audiometry (ATA) could increase access to paediatric hearing assessment in low- and middle-income countries, but few studies have evaluated test-retest repeatability of ATA in children. This study aims to analyse test-retest repeatability of ATA and to identify factors that affect the reliability of this method. DESIGN: ATA was performed twice in a cohort of Nicaraguan schoolchildren. During testing, the proportion of responses occurring in the absence of a stimulus was measured by calculating a stimulus response false positive rate (SRFP). Absolute test-retest repeatability was determined between the two trials, as well as the impact of age, gender, ambient noise, head circumference, and SRFP on these results. STUDY SAMPLE: 807 children were randomly selected from 35 schools in northern Nicaragua. RESULTS: Across all frequencies, the absolute value of the difference between measurements was 5.5 ± 7.8 dB. 89.6% of test-retest differences were within 10 dB. Intra-class correlation coefficients between the two measurements showed that lower SRFP was associated with improved repeatability. No effect of age, gender, or ambient noise was found. CONCLUSIONS: ATA produced moderate test-retest repeatability in Nicaraguan schoolchildren. Participant testing behaviours, such as delayed or otherwise inappropriate response patterns, significantly impacts the repeatability of these measurements.

Prospective measurements of hearing threshold during military rifle training with in-ear, protected, noise exposure monitoring.

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.

School Hearing Screening With a Portable, Tablet-Based, Noise-Attenuating Audiometric Headset in Rural Nicaragua.

OBJECTIVE: To investigate the utility and effectiveness of a noise-attenuating, tablet-based mobile health system combined with asynchronous telehealth evaluations for screening rural Nicaraguan schoolchildren for hearing loss. STUDY DESIGN: Prospective population-based survey. SETTING: Rural Nicaraguan communities. PATIENTS: There were 3,398 school children 7 to 9 years of age. INTERVENTIONS: Diagnostic automated and manual audiometry, detailed asynchronous telehealth evaluations. MAIN OUTCOME MEASURES: Referral rates, ambient noise levels, and audiometric results as well as hearing loss prevalence, types, and risk factors. RESULTS: Despite high ambient noise levels during screening (46.7 dBA), no effect of noise on referral rates on automated audiometry or confirmatory manual audiometry in those who failed automated testing was seen. The overall audiometric referral rate was 2.6%. Idiopathic sensorineural hearing loss (SNHL) and cerumen impaction were the most common types of hearing loss in this population with an estimated prevalence of hearing loss (all types) of 18.3 per 1,000 children. SNHL was associated with both drug exposure during pregnancy (p = 0.04) and pesticide exposure in the home (p = 0.03). CONCLUSION: Hearing screening using a tablet-based, noise-attenuating wireless headset audiometer is feasible and effective in rural low-resource environments with moderately elevated ambient noise levels. The referral rate with noise-attenuating headsets was much lower than that previous reports on this population. In addition, manual audiometry resulted in much lower referral rates than automated audiometry. The confirmed hearing loss rate in this study is comparable to reports from other low-income countries that use some form of noise attenuation during screening. Pesticide exposure and drug exposure during pregnancy are potential causes of SNHL in this population.

International Multicenter Registry for Hyperbaric Oxygen Therapy: Results through June 2021.

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

Community health workers and mHealth systems for hearing screening in rural Nicaraguan schoolchildren.

Background: We aimed to investigate the effectiveness of using minimally trained community health workers (CHW) to screen schoolchildren in rural Nicaragua for hearing loss using a tablet-based audiometric system integrated with asynchronous telehealth evaluations and mobile health (mHealth) appointment reminders. Methods: A population-based survey was conducted using community health workers (CHWs) to perform tablet-based audiometry, asynchronous telehealth evaluations, and mHealth reminders to screen 3398 school children (7-9 years of age) in 92 rural Nicaraguan communities. The accuracy of screening, test duration, testing efficiency, telehealth data validity, and compliance with recommended clinic visits were analyzed. Results: Minimally trained CHWs successfully screened children within remote rural schools with automated audiometry (test duration = 5.8 minutes) followed by manual audiometry if needed (test duration = 4.3 minutes) with an estimated manual audiometry validity of 98.5% based on a review of convergence patterns. For children who were referred based on audiometry, the otoscopy and tympanometry obtained during telehealth evaluations were high quality (as reviewed by 3 experts) in 44.6% and 80.1% of ears, respectively. A combination of automated short message service (SMS) text messages and voice reminders resulted in a follow-up compliance of 75.2%. No families responded to SMS messages alone. Conclusions: Tablet-based hearing screening administered by minimally trained CHWs is feasible and effective in low- and middle-income countries. Manual audiometry was as efficient as automated audiometry in this setting. The physical exam tasks of otoscopy and tympanometry require additional training. Mobile phone messages improve compliance for confirmatory audiometry, but the utility of SMS messaging alone is unclear in this population.

Nonverbal Neurocognitive Assessment during the Coronavirus Disease of 2019 Pandemic: the Effect of Personal Protective Equipment.

OBJECTIVE: The coronavirus disease of 2019 pandemic has increased personal protective equipment (PPE) use in medical settings. The current study examined the effect of PPE on a nonverbal measure of neurocognitive functioning. METHODS: The Leiter International Performance Scale, Third Edition (Leiter-3) was administered to 125 children between the ages of three and eight. Fifty-nine children were assessed twice without any PPE and 66 were assessed once without and once with PPE. Group differences on composite scores were evaluated using a repeated measures design, accounting for sex, school attendance, socioeconomic status, and HIV status. RESULTS: Nonverbal IQ scores increased significantly between test administrations for both groups, but no significant interaction between PPE group and scores on Leiter-3 composites was found. CONCLUSIONS: No main effect of PPE on Leiter-3 outcomes was found. These results suggest clinical and research work using a nonverbal neurocognitive assessment can be completed when PPE is required.

The Resting State Central Auditory Network: a Potential Marker of HIV-Related Central Nervous System Alterations.

OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.

Peripheral Auditory Function in Young HIV-Positive Adults With Clinically Normal Hearing.

OBJECTIVE: Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV. STUDY DESIGN: Matched cohort study with repeated measures. SETTING: Infectious disease center in Dar es Salaam, Tanzania. METHODS: Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses. RESULTS: HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear. CONCLUSION: Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age.