When to Start Computer-Based Auditory Training After Cochlear Implantation: Effects on Quality of Life and Speech Recognition.

OBJECTIVE: Computer-based auditory training (CBAT) has been shown to improve outcomes in adult cochlear implant (CI) users. This study evaluates in new CI users whether starting CBAT within 3 months of activation or later impacts CI outcomes. STUDY DESIGN: Prospective natural experiment. SETTING: Tertiary academic medical center. PATIENTS: Sixty-five new adult CI users. INTERVENTIONS: CBAT use over the first-year postactivation. MAIN OUTCOME MEASURES: Speech recognition scores and CIQOL-35 Profile score improvements between CI recipients who started CBAT resources early (<3 mo) and late (3-12 mo) postactivation. RESULTS: A total of 43 CI recipients started using CBAT within 3 months postactivation (early) and 22 after 3 months (late). Patients who used CBAT within 3 months postactivation showed significantly greater improvement in consonant-nucleus-consonant words (CNCw) (48.3 ± 24.2% vs 27.8 ± 24.9%; d = 0.84), AzBio Sentences in quiet (55.1 ± 28.0% vs 35.7 ± 36.5%; d = 0.62), and CIQOL-35 listening domain scores (18.2 ± 16.3 vs 6.9 ± 12.9, d = 0.73 [0.023, 1.43]), at 3 months postactivation, compared to those who had not yet initiated CBAT. However, by 12 months postactivation, after which all CI recipients had started CBAT, there were no differences observed between patients who started CBAT early or late in speech recognition scores (CNCw: d = 0.26 [-0.35, 0.88]; AzBio: d = 0.37 [-0.23, 0.97]) or in any CIQOL global or domain score (d-range = 0.014-0.47). CONCLUSIONS: Auditory training with self-directed computer software (CBAT) may yield speech recognition and quality-of-life benefits for new adult CI recipients. While early users showed greater improvement in outcomes at 3 months postactivation than users who started later, both groups achieved similar benefits by 12 months postactivation.

Plasma concentrations of multiple oxysterols and risk of colorectal adenomas.

Oxysterols are metabolites of cholesterol that regulate homeostasis of cholesterol, fatty acids, and glucose. These metabolites are generated throughout the body, either enzymatically or from oxidative stress, and are detectable in peripheral circulation. We previously reported that circulating 27-hydroxycholesterol (27-OHC), an endogenous selective estrogen receptor modulator, may be a risk factor for colorectal adenomas. Here, in addition to 27-OHC, we report on four other circulating oxysterols: 25-hydroxycholesterol (25-OHC), 24(S)-hydroxycholesterol (24(S)-OHC), 7ɑ-hydroxycholesterol (7ɑ-OHC), and 4ß-hydroxycholesterol (4ß-OHC). Oxysterol concentrations were measured using liquid chromatography-mass spectrometry from fasting plasma collected at baseline from 1,246 participants of the Vitamin D/Calcium Polyp Prevention Study, a multicenter adenoma chemoprevention trial. To evaluate multiple oxysterols simultaneously, we used both log-linear regression and Bayesian kernel machine regression (BKMR) models developed for analyses of complex mixtures adjusted for potential confounding factors. Higher circulating 7ɑ-OHC was associated with higher adenoma risk (BKMR-based multivariable-adjusted risk ratios, RR, for the 75th vs. 25th percentile, 1.22; 95% credible interval, CI, 1.04-1.42). In contrast, higher circulating 4ß-OHC was associated with lower risk of these polyps (RR, 0.84; 95% CI, 0.71-0.99). The positive association with advanced adenoma risk that we previously reported for circulating 27-OHC persisted when controlling for other oxysterols (RR, 1.26; 95% CI, 0.98-1.62), including among those with advanced adenomas at baseline (RR, 1.75; 95% CI, 1.01-3.06).

Associations of Primary Spoken Language With Individual Perception of Hearing-Related Disability.

OBJECTIVES: Hispanic/Latino adults are less likely than non-Hispanic White adults to seek treatment for hearing disability. While differential socioeconomic factors may contribute to this finding, differences in phonology and syntax in the Spanish, versus English, language may also influence patient perception of hearing disability. The objective of this study is to investigate the association between primary language spoken and participant perception of hearing disability. DESIGN: This study represents a cross-sectional cohort study using National Health and Nutrition Examination Study cycles 2015-2016 and 2017-2020 data. Multivariable logistic regressions estimated the association between respondent-selected interview language, which was used as a proxy for primary spoken language, and participant perception of hearing disability. Models were adjusted for age, gender, highest degree of education, pure-tone average, and self-reported general health. Participants included 4687 individuals from the United States population who elected to speak English (n = 4083) or Spanish (n = 604) during the interview. Perception of hearing disability was assessed by (1) frequency of reported difficulty in following a conversation in noise, (2) frequency with which hearing caused respondents to experience frustration when talking with members of their family or friends, and (3) participants' subjective overall assessment of their hearing. RESULTS: Speaking Spanish, versus English, as a primary language was associated with a 42% lower odds of reporting difficulty hearing and understanding in background noise (odds ratio [OR]: 0.58, 95% confidence interval [CI]: 0.48 to 0.70). Spanish speakers had 28% lower odds of reporting feeling frustrated when talking to family members or friends due to hearing (OR: 0.72, 95% CI: 0.59 to 0.88) as compared with the English-speaking cohort. Speaking Spanish additionally conferred 31% lower odds of describing their own general hearing as "a little trouble to deaf" than participants speaking English (OR: 0.69, 95% CI: 0.53 to 0.90). These observed associations were independent of age, gender, highest degree of education, better pure-tone average? and self-reported general health. CONCLUSIONS: Primary Spanish speakers may be less likely than English speakers to report hearing-related disability, an effect which may be independent of ethnicity. Patient perception of hearing-related disability is an important component of the assessment of and counseling for hearing-related disability and discussion of the need for amplification or other hearing intervention.

Demographic factors impact the rate of hearing decline across the adult lifespan.

BACKGROUND: Little is known about the natural history of hearing loss in adults, despite it being an important public health problem. The purpose of this study is to describe the rate of hearing change per year over the adult lifespan. METHODS: The 1436 participants are from the MUSC Longitudinal Cohort Study of Age-related Hearing Loss (1988-present). Outcomes are audiometric thresholds at 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz, averaged across right and left ears, and pure-tone average (PTA). Demographic factors are sex (female/male), race, which is categorized as white or racial Minority, and baseline age group (18-39, 40-59, 60-69, 70+ years). Linear mixed regression models are used to estimate the effect of age (per year) on the rate of threshold and PTA change. RESULTS: Participants' mean age is 63.1 (SD 14.9) years, 57.7% are female, and 17.8% are racial Minority (17.1% were Black or African American). In sex-race-adjusted models, rates of threshold change are 0.42 to 1.44 dB across thresholds. Rates of change differ by sex at most individual thresholds, but not PTA. Females (versus males) showed higher rates of threshold change in higher frequencies but less decline per year in lower frequencies. Black/African American (versus white) participants have lower rates of threshold and PTA change per year. Hearing thresholds decline across the adult lifespan, with older (versus younger) baseline age groups showing higher rates of decline per year. CONCLUSIONS: Declines to hearing occur across the adult lifespan, and the rate of decline varies by sex, race, and baseline age.

Hearing loss is a common health condition, yet little is known about how hearing changes over time. In this study of 1436 individuals from across the adult lifespan, declines in hearing occurred throughout adulthood. The rate of decline per year varied by sex, in that females experienced more decline in higher pitches but less decline in lower pitches. The rate of decline per year varied by race, in that Black/African American (versus white) participants showed lower rates of hearing decline per year. The rate of decline per year also varied by age, in that older (versus younger) baseline age groups had higher rates of hearing decline per year. This study contributes to understanding of the natural history of hearing loss and could be used to better understand how to focus efforts to prevent and/or manage hearing loss across populations.

Routine Hearing Screening for Older Adults in Primary Care: Insights of Patients and Clinic Personnel.

BACKGROUND AND OBJECTIVES: Hearing loss frequently goes undiagnosed and untreated, with serious sequelae. Hearing screening facilitates diagnosis and treatment but is not routinely conducted in primary care. This study addresses attitudes and insights of patients and primary care clinic personnel relative to routinization of hearing screening in primary care for older adults. RESEARCH DESIGN AND METHODS: Data presented are from the qualitative portion of a larger study. The main study compared screening completion for three approaches to coordinating telephone-based hearing screening with primary care - one offering hearing screening within the primary care encounter and two providing information for at-home screening (one with and one without provider encouragement). Focus groups/interviews were conducted with personnel (n=38) at the six participating clinics, patients who completed screening and were referred for diagnosis (n=14) and patients who did not complete screening (n=10). Analysis used the general inductive approach. RESULTS: Most patients had unaddressed hearing concerns prior to the study. Negative attitudes towards hearing loss/treatment were common, and experiences of family and friends influenced attitudes, but lack of urgency was the primary barrier to screening completion. Respondents favored routine primary care-based hearing screening for older adults, but clinic personnel noted challenges of time, space, workflow, and reimbursement. DISCUSSION AND IMPLICATIONS: Findings favor greater routinization of hearing screening in primary care. Routinization will be enhanced by improved reimbursement for screening and follow-up; specialist engagement with primary care and the public (including leveraging older adults' social networks); and further research on specific integration options.

Change on the Revised Hearing Handicap Inventory and associated factors: results from a longitudinal cohort study.

OBJECTIVE: Describe how the Revised Hearing Handicap Inventory (RHHI) changes over time and determine associated factors. DESIGN: Data were from a community-based cohort study. Linear regression models were used to estimate mean baseline and final RHHI scores and change (final minus baseline score). Logistic regression models were used to determine factors associated with substantial RHHI change, defined as ±6 points. Factors included baseline age, sex, race, hearing aid use, and baseline pure-tone average (PTA; 0.5, 1.0, 2.0, 4.0 kHz, worse ear). STUDY SAMPLE: This study included 583 participants (mean age: 66.4 [SD 9.1] years; 59.9% female; 14.2% Minority race) with a mean follow-up time of 7.6 (SD 4.9) years. RESULTS: Baseline and final RHHI scores were 7.9 and 9.2 points, corresponding to an average 1.3-point increase in hearing difficulty over time. Most participants (65.4%) did not show substantial RHHI change, whereas 21.4% and 13.2% experienced substantial increase and decrease, respectively. In separate multivariable models, PTA and hearing aid use were associated with substantial increase in hearing difficulty, and PTA was associated with substantial decrease. CONCLUSIONS: The average RHHI change was relatively small. Hearing aid use and PTA were associated with RHHI change.

Extended High-Frequency Thresholds: Associations With Demographic and Risk Factors, Cognitive Ability, and Hearing Outcomes in Middle-Aged and Older Adults.

OBJECTIVES: This study had two objectives: to examine associations between extended high-frequency (EHF) thresholds, demographic factors (age, sex, race/ethnicity), risk factors (cardiovascular, smoking, noise exposure, occupation), and cognitive abilities; and to determine variance explained by EHF thresholds for speech perception in noise, self-rated workload/effort, and self-reported hearing difficulties. DESIGN: This study was a retrospective analysis of a data set from the MUSC Longitudinal Cohort Study of Age-related Hearing Loss. Data from 347 middle-aged adults (45 to 64 years) and 694 older adults (≥ 65 years) were analyzed for this study. Speech perception was quantified using low-context Speech Perception In Noise (SPIN) sentences. Self-rated workload/effort was measured using the effort prompt from the National Aeronautics and Space Administration-Task Load Index. Self-reported hearing difficulty was assessed using the Hearing Handicap Inventory for the Elderly/Adults. The Wisconsin Card Sorting Task and the Stroop Neuropsychological Screening Test were used to assess selected cognitive abilities. Pure-tone averages representing conventional and EHF thresholds between 9 and 12 kHz (PTA(9 - 12 kHz)) were utilized in simple linear regression analyses to examine relationships between thresholds and demographic and risk factors or in linear regression models to assess the contributions of PTA(9 - 12 kHz) to the variance among the three outcomes of interest. Further analyses were performed on a subset of individuals with thresholds ≤ 25 dB HL at all conventional frequencies to control for the influence of hearing loss on the association between PTA(9 - 12 kHz) and outcome measures. RESULTS: PTA(9 - 12 kHz) was higher in males than females, and was higher in White participants than in racial Minority participants. Linear regression models showed the associations between cardiovascular risk factors and PTA(9 - 12 kHz) were not statistically significant. Older adults who reported a history of noise exposure had higher PTA(9 - 12 kHz) than those without a history, while associations between noise history and PTA(9 - 12 kHz) did not reach statistical significance for middle-aged participants. Linear models adjusting for age, sex, race and noise history showed that higher PTA(9 - 12 kHz) was associated with greater self-perceived hearing difficulty and poorer speech recognition scores in noise for both middle-aged and older participants. Workload/effort was significantly related to PTA(9 - 12 kHz) for middle-aged, but not older, participants, while cognitive task performance was correlated with PTA(9 - 12 kHz) only for older participants. In general, PTA(9 - 12 kHz)did not account for additional variance in outcome measures as compared to conventional pure-tone thresholds, with the exception of self-reported hearing difficulties in older participants. Linear models adjusting for age and accounting for subject-level correlations in the subset analyses revealed no association between PTA(9 - 12 kHz)and outcomes of interest. CONCLUSIONS: EHF thresholds show age-, sex-, and race-related patterns of elevation that are similar to what is observed for conventional thresholds. The current results support the need for more research to determine the utility of adding EHF thresholds to routine audiometric assessment with middle-aged and older adults.

Attenuation and distortion components of age-related hearing loss: Contributions to recognizing temporal-envelope filtered speech in modulated noise.

Older adults with hearing loss may experience difficulty recognizing speech in noise due to factors related to attenuation (e.g., reduced audibility and sensation levels, SLs) and distortion (e.g., reduced temporal fine structure, TFS, processing). Furthermore, speech recognition may improve when the amplitude modulation spectrum of the speech and masker are non-overlapping. The current study investigated this by filtering the amplitude modulation spectrum into different modulation rates for speech and speech-modulated noise. The modulation depth of the noise was manipulated to vary the SL of speech glimpses. Younger adults with normal hearing and older adults with normal or impaired hearing listened to natural speech or speech vocoded to degrade TFS cues. Control groups of younger adults were tested on all conditions with spectrally shaped speech and threshold matching noise, which reduced audibility to match that of the older hearing-impaired group. All groups benefitted from increased masker modulation depth and preservation of syllabic-rate speech modulations. Older adults with hearing loss had reduced speech recognition across all conditions. This was explained by factors related to attenuation, due to reduced SLs, and distortion, due to reduced TFS processing, which resulted in poorer auditory processing of speech cues during the dips of the masker.

Targeting endothelial cell anergy to improve CAR T cell therapy for solid tumors.

Chimeric antigen receptor (CAR) T cell therapy presents significant results, especially for the treatment of hematologic malignancies. However, there are limitations and challenges to be overcome to achieve similar success for the treatment of solid tumors. These challenges involve selection of the target, infiltration into the tumor microenvironment and maintenance of functionality. The tumor vasculature is a major barrier for leukocytes to enter the tumor parenchyma. Due to the exposure of the vasculature to angiogenic growth factors during tumor progression, the endothelial cells become anergic to inflammatory cytokines, resulting in reduced leukocyte adhesion molecule expression. As such adhesion molecules are a prerequisite for leukocyte extravasation, endothelial cell anergy allows tumors to escape from endogenous immunity, as well as from cellular immunotherapies such as CAR T cells. Hence, overcoming endothelial cell anergy, e.g. through the administration of angiogenesis inhibitors, is believed to restore anti-tumor immunity. Concomitantly, both endogenous immune cells as well as cellular therapeutics such as CAR T cells can permeate into the tumor parenchyma. Here, we discuss how prior or concomitant treatment with an antiangiogenic drug can improve CAR T cell therapy, to become an attractive strategy for the treatment of solid tumors.

Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart against ischemia/reperfusion injury by limiting TNFα-induced mitochondrial injury in experimental diabetes.

AIMS: The histone deacetylase 6 (HDAC6) inhibitor, tubastatin A, reduces myocardial ischemia/reperfusion injury (MIRI) in type 1 diabetic rats. It remains unclear whether HDAC6 regulates MIRI in type 2 diabetic animals. Diabetes augments activity of HDAC6 and generation of tumor necrosis factor α (TNFα) and impairs mitochondrial complex I (mCI). Here we examined how HDAC6 regulates TNFα production, mCI activity, mitochondria, and cardiac function in type 1 and type 2 diabetic mice undergoing MIRI. METHODS AND RESULTS: HDAC6 knockout, streptozotocin-induced type 1 diabetic, and obese type 2 diabetic db/db mice underwent MIRI in vivo or ex vivo in a Langendorff-perfused system. We found that MIRI and diabetes additively augmented myocardial HDAC6 activity and generation of TNFα, along with cardiac mitochondrial fission, low bioactivity of mCI, and low production of ATP. Importantly, genetic disruption of HDAC6 or tubastatin A decreased TNFα levels, mitochondrial fission, and myocardial mitochondrial NADH levels in ischemic/reperfused diabetic mice, concomitant with augmented mCI activity, decreased infarct size, and improved cardiac function. Moreover, HDAC6 knockout or tubastatin A treatment decreased left ventricular dilation and improved cardiac systolic function 28 days after MIRI. H9c2 cardiomyocytes with and without HDAC6 knockdown were subjected to hypoxia/reoxygenation injury in the presence of high glucose. Hypoxia/reoxygenation augmented HDAC6 activity and TNFα levels and decreased mCI activity. These negative effects were blocked by HDAC6 knockdown. CONCLUSIONS: HDAC6 is an essential negative regulator of MIRI in diabetes. Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart from MIRI by limiting TNFα-induced mitochondrial injury in experimental diabetes.

Emerging Indications for Hyperbaric Oxygen Treatment: Registry Cohort Study.

BACKGROUND: Hyperbaric oxygen (HBO2) treatment is used across a range of medical specialties for a variety of applications, particularly where hypoxia and inflammation are important contributors. Because of its hypoxia-relieving and anti-inflammatory effects HBO2 may be useful for new indications not currently approved by the Undersea and Hyperbaric Medical Society. Identifying these new applications for HBO2 is difficult because individual centers may only treat a few cases and not track the outcomes consistently. The web-based International Multicenter Registry for Hyperbaric Oxygen Therapy captures prospective outcome data for patients treated with HBO2 therapy. These data can then be used to identify new potential applications for HBO2, which has relevance for a range of medical specialties. OBJECTIVE: Although hyperbaric medicine has established indications, new ones continue to emerge. One objective of this registry study was to identify cases where HBO2 has been used for conditions falling outside of current Undersea and Hyperbaric Medical Society-approved indications and present outcome data for them. METHODS: This descriptive study used data from a web-based, multicenter, international registry of patients treated with HBO2. Participating centers agree to collect data on all patients treated using standard outcome measures, and individual centers send deidentified data to the central registry. HBO2 treatment programs in the United States, the United Kingdom, and Australia participate. Demographic, outcome, complication, and treatment data, including pre- and posttreatment quality of life questionnaires (EQ-5D-5L) were collected for individuals referred for HBO2 treatment. RESULTS: Out of 9726 patient entries, 378 (3.89%) individuals were treated for 45 emerging indications. Post-COVID-19 condition (PCC; also known as postacute sequelae of COVID-19; 149/378, 39.4%), ulcerative colitis (47/378, 12.4%), and Crohn disease (40/378, 10.6%) accounted for 62.4% (n=236) of the total cases. Calciphylaxis (20/378, 5.3%), frostbite (18/378, 4.8%), and peripheral vascular disease-related wounds (12/378, 3.2%) accounted for a further 13.2% (n=50). Patients with PCC reported significant improvement on the Neurobehavioral Symptom Inventory (NSI score: pretreatment=30.6; posttreatment=14.4; P<.001). Patients with Crohn disease reported significantly improved quality of life (EQ-5D score: pretreatment=53.8; posttreatment=68.8), and 5 (13%) reported closing a fistula. Patients with ulcerative colitis and complete pre- and post-HBO2 data reported improved quality of life and lower scores on a bowel questionnaire examining frequency, blood, pain, and urgency. A subset of patients with calciphylaxis and arterial ulcers also reported improvement. CONCLUSIONS: HBO2 is being used for a wide range of possible applications across various medical specialties for its hypoxia-relieving and anti-inflammatory effects. Results show statistically significant improvements in patient-reported outcomes for inflammatory bowel disease and PCC. HBO2 is also being used for frostbite, pyoderma gangrenosum, pterygium, hypospadias repair, and facial filler procedures. Other indications show evidence for improvement, and the case series for all indications is growing in the registry. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/18857.

Implications of lung shunt fraction calculation discrepancy in Yttrium-90 radioembolization treatment from 2D planar vs 3D single photon emission CT imaging.

The safety and efficacy of Yttrium-90 (Y-90) radio-embolization therapy is partly dependent on the lung shunt fraction (LSF). There may be a notable disparity between LSF when calculated using 2D planar imaging vs 3D single photon emission CT (SPECT); this can affect the total allowable Y-90 dose delivered and therefore change the effectiveness of the procedure. The case presented demonstrates an 81% decrease in LSF when calculated by SPECT as compared to 2D planar imaging. This case highlights the importance of considering the imaging technique and the potential discrepancies that can arise between planar and SPECT imaging in LSF assessment.

Prevalence of self-reported hearing difficulty on the Revised Hearing Handicap Inventory and associated factors.

BACKGROUND: Hearing loss is common in aging adults and is an important public health concern. Self-reported measures of hearing difficulty are often used in research and clinical practice, as they capture the functional impacts of hearing loss on individuals. However, little research has evaluated the prevalence or factors associated with self-reported hearing difficulty. Therefore, the purpose of this study was to determine the prevalence of self-reported hearing difficulty, measured by the Revised Hearing Handicap Inventory (RHHI), and associated factors. METHODS: This study was conducted in a community-based cohort study based in Charleston, SC. We determined the prevalence of RHHI self-reported hearing difficulty (score ≥ 6 points) and evaluated associated factors with logistic regression models. Results are presented as odds ratios (OR) with corresponding 95% confidence intervals (95% CI). RESULTS: There were 1558 participants included in this study (mean age 63.7 [SD 14.4], 56.9% female, 20.0% Minority race). The prevalence of RHHI self-reported hearing difficulty was 48.8%. In a multivariable model, older age (per + 1 year; OR 0.97 [95% CI 0.96, 0.98]), Minority (vs. White) race (OR 0.68 [95% CI 0.49, 0.94]), and speech-in-noise scores that are better than predicted (OR 0.99 [95% CI 0.98, 1.00]) were associated with lower odds of RHHI self-reported hearing difficulty. Furthermore, female (vs. male) sex (OR 1.39 [95% CI 1.03, 1.86]), higher PTA in the worse ear (per + 1 dB; OR 1.10 [95% CI 1.09, 1.12]), more comorbid conditions (vs. 0; 1 condition: OR 1.50 [95% CI 1.07, 2.11]; 2 conditions: OR 1.96 [95% CI 1.32, 2.93]; 3 + conditions: OR 3.00 [95% CI 1.60, 5.62]), noise exposure (OR 1.54 [95% CI 1.16, 2.03]), bothersome tinnitus (OR 2.16 [95% CI 1.59, 2.93]), and more depressive symptoms (OR 1.04 [95% CI 1.01, 1.07]) were associated with higher odds of RHHI self-reported hearing difficulty. CONCLUSIONS: The prevalence of RHHI self-reported hearing difficulty is high, and associated factors included demographics, audiometric hearing and other hearing-related factors, and physical and mental health. The RHHI likely captures functional impacts of hearing loss that are not captured by audiometry alone. Study findings can support the correct interpretation of the RHHI in research and clinical settings.

Factors Affecting Postpartum Bone Mineral Density in a Clinical Trial of Vitamin D Supplementation.

Background: Few studies evaluate the effects of vitamin D status and supplementation on maternal bone mineral density (BMD) during lactation and further lack inclusion of diverse racial/ethnic groups, body mass index (BMI), or physical activity. Objective: Determine the effects of vitamin D treatment/status, feeding type, BMI, race/ethnicity, and physical activity on postpartum women's BMD to 7 months. Methods: Women with singleton pregnancies beginning 4-6 weeks' postpartum were randomized into two treatment groups (400 or 6400 IU vitamin D/day). Participant hip, spine, femoral neck, and whole-body BMD using Dual-energy X-ray absorptiometry (DXA Hologic), serum 25-hydroxyvitamin D [25(OH)D] (RIA; Diasorin), BMI, and physical activity were measured at 1, 4, and 7 months postpartum. A general linear mixed modeling approach was undertaken to assess the effects of vitamin D status [both serum 25(OH)D concentrations and treatment groups], feeding type, race/ethnicity, BMI, and physical activity on BMD in postpartum women. Results: During the 6-month study period, lactating women had 1-3% BMD loss in all regions compared with 1-3% gain in nonlactating women. Higher maternal BMI was associated with less bone loss in femoral neck and hip regions. Black American women had less BMD loss than White/Caucasian or Hispanic lactating women in spine and hip regions. Exclusively breastfeeding women in the 6400 IU vitamin D group had less femoral neck BMD loss than the 400 IU group at 4 months sustained to 7 months. Physical activity was associated with higher hip BMD. Conclusion: While there was BMD loss during lactation to 7 months, the loss rate was less than previously reported, with notable racial/ethnic variation. Breastfeeding was associated with loss in BMD compared with formula-feeding women who gained BMD. Higher BMI and physical activity independently appeared to protect hip BMD, whereas higher vitamin D supplementation appeared protective against femoral neck BMD loss.

Agreement between audiometric hearing loss and self-reported hearing difficulty on the Revised Hearing Handicap Inventory differs by demographic factors.

BACKGROUND: New standardised measures of self-reported hearing difficulty can be validated against audiometric hearing loss. This study reports the influence of demographic factors (age, sex, race and socioeconomic position (SEP)) on the agreement between audiometric hearing loss and self-reported hearing difficulty. METHODS: Participants were 1558 adults (56.9% female; 20.0% racial minority; mean age 63.7 (SD 14.1) years) from the Medical University of South Carolina Longitudinal Cohort Study of Age-Related Hearing Loss (1988-current). Audiometric hearing loss was defined as the average of pure-tone thresholds at frequencies 0.5, 1.0, 2.0 and 4.0 kHz >25 dB HL in the worse ear. Self-reported hearing difficulty was defined as ≥6 points on the Revised Hearing Handicap Inventory (RHHI) or RHHI screening version (RHHI-S). We report agreement between audiometric hearing loss and the RHHI(-S), defined by sensitivity, specificity, accuracy, positive predictive value, negative predictive value and observed minus predicted prevalence. Estimates were stratified to age group, sex, race and SEP proxy. RESULTS: The prevalence of audiometric hearing loss and self-reported hearing difficulty were 49.0% and 48.8%, respectively. Accuracy was highest among participants aged <60 (77.6%) versus 60-70 (71.4%) and 70+ (71.9%) years, for white (74.6%) versus minority (68.0%) participants and was similar by sex and SEP proxy. Generally, agreement of audiometric hearing loss and RHHI(-S) self-reported hearing difficulty differed by age, sex and race. CONCLUSIONS: Relationships of audiometric hearing loss and self-reported hearing difficulty vary by demographic factors. These relationships were similar for the full (RHHI) and screening (RHHI-S) versions of this tool.

Effects of age and noise exposure history on auditory nerve response amplitudes: A systematic review, study, and meta-analysis.

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization.

Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo-fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material- and pregnancy stage-specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO2) and titanium dioxide (TiO2) NPs) and environmental NPs (diesel exhaust particles, DEPs). This includes a multitude of secreted inflammatory, vascular, and endocrine placental factors as well as extracellular vesicle (EV)-associated proteins. Moreover, conditioned media (CM) from NP-exposed explants induce pronounced anti-angiogenic and anti-vasculogenic effects, while early neurodevelopmental processes are only marginally affected. These findings underscore the potential of metal oxide NPs and DEPs for widespread interference with the placental secretome and identify vascular morphogenesis as a sensitive outcome for the indirect developmental toxicity of different NPs. Overall, this work has profound implications for the future safety assessment of NPs for industrial, commercial, or medical applications in pregnancy, which should consider placenta-mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies.

Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies.

INTRODUCTION: To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test). RESEARCH DESIGN AND METHODS: Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics. RESULTS: Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m2, r=0.35). CONCLUSIONS: Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.