The Effects of Delayed Cord Clamping on 12-Month Brain Myelin Content and Neurodevelopment: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine if delayed cord clamping (DCC) affected brain myelin water volume fraction (VFm) and neurodevelopment in term infants. STUDY DESIGN: This was a single-blinded randomized controlled trial of healthy pregnant women with term singleton fetuses randomized at birth to either immediate cord clamping (ICC) (≤ 20 seconds) or DCC (≥ 5 minutes). Follow-up at 12 months of age consisted of blood work for serum iron indices and lead levels, a nonsedated magnetic resonance imaging (MRI), followed within the week by neurodevelopmental testing. RESULTS: At birth, 73 women were randomized into one of two groups: ICC (the usual practice) or DCC (the intervention). At 12 months, among 58 active participants, 41 (80%) had usable MRIs. There were no differences between the two groups on maternal or infant demographic variables. At 12 months, infants who had DCC had increased white matter brain growth in regions localized within the right and left internal capsules, the right parietal, occipital, and prefrontal cortex. Gender exerted no difference on any variables. Developmental testing (Mullen Scales of Early Learning, nonverbal, and verbal composite scores) was not significantly different between the two groups. CONCLUSION: At 12 months of age, infants who received DCC had greater myelin content in important brain regions involved in motor function, visual/spatial, and sensory processing. A placental transfusion at birth appeared to increase myelin content in the early developing brain. KEY POINTS: · DCC resulted in higher hematocrits in newborn period.. · DCC appears to increase myelin at 12 months.. · Gender did not influence study outcomes..

Reliability of Serological Prestin Levels in Humans and its Relation to Otoacoustic Emissions, a Functional Measure of Outer Hair Cells.

OBJECTIVES: Serological biomarkers, common to many areas of medicine, have the potential to inform on the health of the human body and to give early warning of risk of compromised function or illness before symptoms are experienced. Serological measurement of prestin, a motor protein uniquely produced and expressed in outer hair cells, has recently been identified as a potential biomarker to inform on the health of the cochlea. Before any test can be introduced into the clinical toolkit, the reproducibility of the measurement when repeated in the same subject must be considered. The primary objective of this study is to outline the test-retest reliability estimates and normative ranges for serological prestin in healthy young adults with normal hearing. In addition, we examine the relation between serum prestin levels and otoacoustic emissions (OAEs) to compare this OHC-specific protein to the most common measure of OHC function currently used in hearing assessments. DESIGN: We measured prestin levels serologically from circulating blood in 34 young adults (18 to 24 years old) with clinically normal pure-tone audiometric averages at five different timepoints up to six months apart (average intervals between measurements ranged from <1 week to 7 weeks apart). To guide future studies of clinical populations, we present the standard error of the measurement, reference normative values, and multiple measures of reliability. Additionally, we measured transient evoked OAEs at the same five timepoints and used correlation coefficients to examine the relation between OAEs and prestin levels (pg/mL). RESULTS: Serum prestin levels demonstrated good to excellent reliability between and across the five different time points, with correlation coefficients and intraclass correlations >0.8. Across sessions, the average serum prestin level was 250.20 pg/mL, with a standard error of measurement of 7.28 pg/mL. Moreover, positive correlations (generally weak to moderate) were found between prestin levels and OAE magnitudes and signal-to-noise ratios. CONCLUSIONS: Findings characterize serum prestin in healthy young adults with normal hearing and provide initial normative data that may be critical to interpreting results from individuals with sensorineural hearing loss. Our results demonstrate reliability of serum prestin levels in a sample of normal-hearing young adults across five test sessions up to 6 months apart, paving the way for testing larger samples to more accurately estimate test-retest standards for clinical protocols, including those involving serial monitoring. The positive correlations between serum prestin and OAE levels, although weak to moderate, reinforce that the source of serum prestin is likely the outer hair cells in the inner ear, but also that serum prestin and OAEs each may also index aspects of biologic function not common to the other.

The Association Between Mindfulness and Postoperative Pain: A Prospective Cohort Study of Gynecologic Oncology Patients Undergoing Minimally Invasive Hysterectomy.

STUDY OBJECTIVE: To describe the association between preoperative dispositional mindfulness (the personality trait of being mindful) and postoperative pain in gynecologic oncology patients undergoing minimally invasive hysterectomy. DESIGN: Prospective cohort study. SETTING: University-affiliated teaching hospital. PATIENTS: Gynecologic oncology patients (n = 126) planning minimally invasive hysterectomy. INTERVENTIONS: Minimally invasive hysterectomy. MEASUREMENTS AND MAIN RESULTS: Baseline mindfulness was assessed at the preoperative visit using the Five Facet Mindfulness Questionnaire (FFMQ). Postoperative pain and opioid usage were evaluated via chart review and surveys at postoperative visits at 1 to 2 weeks and 4 to 6 weeks. Higher baseline mindfulness was correlated with lower postoperative pain as measured by both the average and highest numeric pain scores during the inpatient stay (r = -.23, p = .020; r = -.21, p = .034). At the initial postoperative visit, pain score was also inversely correlated with preoperative mindfulness score (r = -.26, p = .008). This relationship was not observed at the final postoperative visit (r = -.08, p = .406). Pre-operative mindfulness and opioid usage were also inversely associated, though this relationship did not reach statistical significance (r = -.18, p = .066). CONCLUSION: Mindfulness was previously shown to be a promising intervention for chronic pain treatment. Our study demonstrates that higher preoperative dispositional mindfulness is associated with more favorable postoperative pain outcomes, including lower pain scores but not lower opioid consumption. This relationship provides an opportunity to target the modifiable personality characteristic of mindfulness, to reduce postoperative pain in patients following gynecologic surgery.

A review of inherited cancer susceptibility syndromes.

Inherited cancer syndromes are caused by genetic mutations that place patients at an increased risk for developing cancer. Although most cancers are not caused by genetic inheritance, clinicians must understand these syndromes and be able to recognize their common characteristics. A thorough family history and identification of common patterns as well as specific clinical signs and symptoms can help with early recognition. This article describes symptoms of the more common cancer syndromes, including hereditary breast and ovarian cancer, Li-Fraumeni, Lynch, familial adenomatous polyposis, retinoblastoma, multiple endocrine neoplasia, and von Hippel-Lindau. Important patient education regarding genetic testing also is covered.

Opioid use after minimally invasive hysterectomy in gynecologic oncology patients.

OBJECTIVES: To quantify, and identify predictors of, post-discharge opioid use in gynecologic oncology patients undergoing minimally invasive hysterectomy (MIH). METHODS: For this prospective cohort study, gynecologic oncology patients planning to undergo MIH were recruited at a single institution. Post-operative opioid usage was evaluated via chart review and surveys at 1-2-week and 4-6-week post-operative visits. Opioids are converted to oral morphine milligram equivalents (MME) for standardization. Descriptive statistics and modified Poisson regression were used to quantify opioid requirements and evaluate predictors of post-discharge opioid use respectively. RESULTS: One hundred eighteen eligible women underwent MIH. Of these, 108 had complete data at both follow-up timepoints. Malignancy was present in 79% of cases, 71% of which were endometrial cancer. Most surgeries were laparoscopic (73%). Median hospital stay was 1 night (IQR 1-1). Inpatients received a median of 30.75 MME (IQR 7.5-52.5 MME). Twenty-three women (21.3%) used no opioids while inpatient. At the 1-2-week follow-up median usage was 6 pills of 5 mg oxycodone, or 45 MME (IQR 0-15.5 pills). After complete follow-up, median post-discharge usage was 10 pills, or 75 MME (IQR 0-22.5 pills) and 36 participants (33.33%) used no opioids after hospital discharge. The median prescription was for 30 pills (range 10-60). Above median inpatient opioid use was associated with an increased risk of above median opioid usage after hospital discharge (RR 2.31, 95% CI 1.38-3.87) on multivariable analysis. CONCLUSIONS: In this cohort, opioids were overprescribed relative to use. Inpatient use was the strongest predictor of post-discharge opioid use. More restrictive, and personalized, opioid prescribing practices may be a pathway to reduce opioid misuse and diversion. PRéCIS: Opioids were overprescribed by a factor of three to gynecologic oncology patients, whose inpatient opioid requirement predicted post-discharge opioid needs after minimally invasive hysterectomy.

Alternative pathways for Escherichia coli biofilm formation revealed by sRNA overproduction.

Small regulatory RNAs have major roles in many regulatory circuits in Escherichia coli and other bacteria, including the transition from planktonic to biofilm growth. We tested Hfq-dependent sRNAs in E. coli for their ability, when overproduced, to inhibit or stimulate biofilm formation, in two different growth media. We identify two mutually exclusive pathways for biofilm formation. In LB, PgaA, encoding an adhesion export protein, played a critical role; biofilm was independent of the general stress factor RpoS or CsgD, regulator of curli and other biofilm genes. The PgaA-dependent pathway was stimulated upon overproduction of DsrA, via negative regulation of H-NS, or of GadY, likely by titration of CsrA. In yeast extract casamino acids (YESCA) media, biofilm was dependent on RpoS and CsgD, but independent of PgaA; RpoS appears to indirectly negatively regulate the PgaA-dependent pathway in YESCA medium. Deletions of most sRNAs had very little effect on biofilm, although deletion of hfq, encoding an RNA chaperone, was defective in both LB and YESCA. Deletion of ArcZ, a small RNA activator of RpoS, decreased biofilm in YESCA; only a portion of this defect could be bypassed by overproduction of RpoS. Overall, sRNAs highlight different pathways to biofilm formation.

Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether placental transfusion influences brain myelination at 4 months of age. STUDY DESIGN: A partially blinded, randomized controlled trial was conducted at a level III maternity hospital in the US. Seventy-three healthy term pregnant women and their singleton fetuses were randomized to either delayed umbilical cord clamping (DCC, >5 minutes) or immediate clamping (ICC, <20 seconds). At 4 months of age, blood was drawn for ferritin levels. Neurodevelopmental testing (Mullen Scales of Early Learning) was administered, and brain myelin content was measured with magnetic resonance imaging. Correlations between myelin content and ferritin levels and group-wise DCC vs ICC brain myelin content were completed. RESULTS: In the DCC and ICC groups, clamping time was 172 ± 188 seconds vs 28 ± 76 seconds (P < .002), respectively; the 48-hour hematocrit was 57.6% vs 53.1% (P < .01). At 4 months, infants with DCC had significantly greater ferritin levels (96.4 vs 65.3 ng/dL, P = .03). There was a positive relationship between ferritin and myelin content. Infants randomized to the DCC group had greater myelin content in the internal capsule and other early maturing brain regions associated with motor, visual, and sensory processing/function. No differences were seen between groups in the Mullen testing. CONCLUSION: At 4 months, infants born at term receiving DCC had greater ferritin levels and increased brain myelin in areas important for early life functional development. Endowment of iron-rich red blood cells obtained through DCC may offer a longitudinal advantage for early white matter development. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01620008.

The ecology of population dispersal: Modeling alternative basin-plateau foraging strategies to explain the Numic expansion.

OBJECTIVES: The expansion of Numic speaking populations into the Great Basin required individuals to adapt to a relatively unproductive landscape. Researchers have proposed numerous social and subsistence strategies to explain how and why these settlers were able to replace any established populations, including private property and intensive plant processing. Here we evaluate these hypotheses and propose a new strategy involving the use of landscape fire to increase resource encounter rates. METHODS: Implementing a novel, spatially explicit, multi-scalar prey choice model, we examine how individual decisions approximating each alternative strategy (private property, anthropogenic fire, and intensive plant processing) would aggregate at the patch and band level to confer an overall benefit to this colonizing population. Analysis relies on experimental data reporting resource profitability and abundance, ecological data on the historic distribution of vegetation patches, and ethnohistoric data on the distribution of Numic bands. RESULTS: Model results show that while resource privatization and landscape fires produce a substantial advantage, intensified plant processing garners the greatest benefit. The relative benefits of alternative strategies vary significantly across ecological patches resulting in variation across ethnographic band ranges. Combined, a Numic strategy including all three alternatives would substantially increase subsistence yields. CONCLUSIONS: The application of a strategy set that includes landscape fire, privatization and intensified processing of seeds and nuts, explains why the Numa were able to outcompete local populations. This approach provides a framework to help explain how individual decisions can result in such population replacement events throughout human history.

Small RNA Regulation of TolC, the Outer Membrane Component of Bacterial Multidrug Transporters.

UNLABELLED: Bacteria use multidrug efflux pumps to export drugs and toxic compounds out of the cell. One of the most important efflux pumps in Escherichia coli is the AcrAB-TolC system. Small regulatory RNAs (sRNAs) are known to be major posttranscriptional regulators that can enhance or repress translation by binding to the 5' untranslated region (UTR) of mRNA targets with the help of a chaperone protein, Hfq. In this study, we investigated the expression of acrA, acrB, and tolC translational fusions using 27 Hfq-dependent sRNAs overexpressed from plasmids. No significant sRNA regulation of acrA or acrB was detected. SdsR (also known as RyeB), an abundant and well-conserved stationary-phase sRNA, was found to repress the expression of tolC, the gene encoding the outer membrane protein of many multidrug resistance efflux pumps. This repression was shown to be by direct base pairing occurring upstream from the ribosomal binding site. SdsR overexpression and its regulation of tolC were found to reduce resistance to novobiocin and crystal violet. Our results suggest that additional targets for SdsR exist that contribute to increased antibiotic sensitivity and reduced biofilm formation. In an effort to identify phenotypes associated with single-copy SdsR and its regulation of tolC, the effect of a deletion of sdsR or mutations in tolC that should block SdsR pairing were investigated using a Biolog phenotypic microarray. However, no significant phenotypes were identified. Therefore, SdsR appears to modulate rather than act as a major regulator of its targets. IMPORTANCE: AcrAB-TolC is a major efflux pump present in E. coli and Gram-negative bacteria used to export toxic compounds; the pump confers resistance to many antibiotics of unrelated classes. In this study, we found that SdsR, a small RNA expressed in stationary phase, repressed the expression of tolC, resulting in increased sensitivity to some antibiotics. This extends the findings of previous studies showing that sRNAs contribute to the regulation of many outer membrane proteins; manipulating or enhancing their action might help in sensitizing bacteria to antibiotics.

Effects of Placental Transfusion on Neonatal and 18 Month Outcomes in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of delayed cord clamping (DCC) vs immediate cord clamping (ICC) on intraventricular hemorrhage (IVH), late onset sepsis (LOS), and 18-month motor outcomes in preterm infants. STUDY DESIGN: Women (n = 208) in labor with singleton fetuses (<32 weeks gestation) were randomized to either DCC (30-45 seconds) or ICC (<10 seconds). The primary outcomes were IVH, LOS, and motor outcomes at 18-22 months corrected age. Intention-to-treat was used for primary analyses. RESULTS: Cord clamping time was 32 ± 16 (DCC) vs 6.6 ± 6 (ICC) seconds. Infants in the DCC and ICC groups weighed 1203 ± 352 and 1136 ± 350 g and mean gestational age was 28.3 ± 2 and 28.4 ± 2 weeks, respectively. There were no differences in rates of IVH or LOS between groups. At 18-22 months, DCC was protective against motor scores below 85 on the Bayley Scales of Infant Development, Third Edition (OR 0.32, 95% CI 0.10-0.90, P = .03). There were more women with preeclampsia in the ICC group (37% vs 22%, P = .02) and more women in the DCC group with premature rupture of membranes/preterm labor (54% vs 75%, P = .002). Preeclampsia halved the risk of IVH (OR 0.50, 95% CI 0.2-1.0) and premature rupture of membranes/preterm labor doubled the risk of IVH (OR 2.0, 95% CI 1.2-4.3). CONCLUSIONS: Although DCC did not alter the incidence of IVH or LOS in preterm infants, it improved motor function at 18-22 months corrected age. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00818220 and NCT01426698.

Early progression during or after cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy indicates poor outcome with rescue protocols in dogs with multicentric lymphoma.

BACKGROUND: Dogs with lymphoma that fail cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (CHOP) before completion of their protocol are commonly thought to have poor long-term outcome, but no previous studies have evaluated the effect of early relapse on progression-free interval (PFI) or overall survival time (OST) for patients undergoing rescue chemotherapy. OBJECTIVE: Correlate rescue treatment outcomes in dogs with multicentric lymphoma with outcomes after 1st-line CHOP chemotherapy. METHODS: Data were collected from 6 previous retrospective or prospective studies in 187 dogs with multicentric lymphoma that received 1st-line CHOP chemotherapy and then received either lomustine (CCNU), L-asparaginase and prednisone (LAP), or rabacfosadine (RAB, Tanovea), with or without prednisone or L-asparaginase. RESULTS: The PFI after initiation of CHOP chemotherapy was significantly associated with response rate postprogression, PFI, and postrescue survival time (ST) for both rescue protocols. Immunophenotype (B- vs T-cell) was not significantly associated with response, PFI or OST for LAP but was significantly associated with response and PFI for RAB. CONCLUSION: Dogs that experience short PFI during or after 1st-line CHOP chemotherapy had lower response rates to rescue treatment, with shorter PFI and ST. Immunophenotype did not significantly affect outcome with LAP but was associated with PFI for RAB.

Unilateral Periorbital Swelling in a Pediatric Patient.

Infratemporal fossa (ITF) tumors are rare in children and may present with a variety of symptoms. Teratomas are neoplasms derived from the 3 germ layers and approximately 6% to 10% are within the head and neck. Our study discusses one of the first reported cases of teratoma in the ITF in a pediatric patient. A 3-year-old girl presents with 2 years of recurrent monthly left periorbital swelling accompanied by fevers, skin discoloration, and pain. Prior episodes were treated with antibiotics with incomplete resolution. Imaging revealed a cystic lesion centered in the ITF. She was taken for endoscopic endonasal biopsy of the lesion and had no complications. Pathology revealed a mature teratoma composed primarily of pancreatic tissue. Providers should consider masses such as teratoma in the differential for ITF tumors and periorbital edema unresponsive to typical treatment.

A daptomycin-xylitol-loaded polymethylmethacrylate bone cement: how much xylitol should be used?

BACKGROUND: The rate of release of an antibiotic from an antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is low. This may be increased by adding a particulate poragen (eg, xylitol) to the cement powder. However, the appropriate poragen amount is unclear. QUESTIONS/PURPOSES: We explored the appropriate amount of xylitol to use in a PMMA bone cement loaded with daptomycin and xylitol. METHODS: We prepared four groups of cement, each comprising the same amount of daptomycin in the powder (1.36 g/40 g dry powder) but different amounts of xylitol (0, 0.7, 1.4, and 2.7 g); the xylitol mass ratio (X) (mass divided by mass of the final dry cement-daptomycin-xylitol mixture) ranged from 0 to 6.13 wt/wt%. Eight mechanical, antibiotic release, and bacterial inhibitory properties were determined using three to 22 specimens or replicates per test. We then used an optimization method to determine an appropriate value of X by (1) identifying the best-fit relationship between the value of each property and X, (2) defining a master objective function incorporating all of the best fits; and (3) determining the value of X at the maximum master objective function. RESULTS: We found an appropriate xylitol amount to be 4.46 wt/wt% (equivalent to 1.93 g xylitol mixed with 1.36 g daptomycin and 40 g dry cement powder). CONCLUSIONS: We demonstrated a method that may be used to determine an appropriate xylitol amount for a daptomycin-xylitol-loaded PMMA bone cement. These findings will require in vivo confirmation. CLINICAL RELEVANCE: While we identified an appropriate amount of xylitol in a daptomycin-xylitol-loaded PMMA bone cement as a prophylactic agent in total joint arthroplasties, clinical evaluations are needed to confirm the effectiveness of this cement.

Antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary vascular surgical site infections.

OBJECTIVE: This study assessed the efficacy of antibiotic-loaded polymethylmethacrylate (PMMA) beads in the treatment of lower extremity vascular surgical site infections (VSSIs). METHODS: This was a retrospective review of all patients with a VSSI of a lower extremity bypass treated with antibiotic-loaded PMMA beads and culture-specific antibiotics during a 4.5-year period. Data collected included patient demographics, comorbidities, site of initial graft infection, symptoms and signs at presentation, initial and additional surgical debridement, wound culture results, type of antibiotic beads implanted, and graft treatment strategy, comprising conduit preservation or in situ replacement, with associated soft tissue management by muscle flap or vacuum-assisted closure. Primary outcome measures included death, recurrent infection, and limb salvage. RESULTS: Forty patients developed 42 extracavitary lower extremity VSSIs (bilateral groin infections in two). Patients were treated according to our treatment algorithm with antibiotic-impregnated PMMA beads. Previous reconstructions included nine aortofemoral bypasses (groin infection only), 20 infrainguinal bypasses, five extra-anatomic bypasses, five femoral interpositions, two combined inflow-outflow bypass procedures, and one patch angioplasty with VSSI. Cultures isolated 59 pathogens (39 gram-positive, 18 gram-negative, 2 Candida spp). Methicillin-resistant Staphylococcus aureus was cultured from 10 VSSs (23.8%) overall and from 27.7% of those patients with attempted graft preservation or in situ reconstructions. Two patients (4.8%) had no growth despite clinical signs of infection. Repeat VSS exploration and culture results led to an average of 1.4 bead replacements before definitive treatment. Final treatment strategy included graft preservation of patent bypasses in 28, partial graft excision with in situ replacement in eight, graft removal only with residual graft remaining at implant site (ie, incorporated anastomotic conduit, 11.9%) in five, and extra-anatomic reconstruction in one. Sartorius muscle flap was performed in 14 groin infections (37.8%). The 30-day mortality was 0%, and limb loss was 7.1% (n = 3). At the median follow-up of 17 months, the limb loss was 21.4% and the recurrent infection rate was 19.4% (seven of 36) in those with attempted graft preservation or in situ replacement. CONCLUSIONS: Antibiotic-loaded PMMA beads may serve as an adjunct in the management of VSSIs and may also expand treatment options for graft preservation or in situ reconstruction, with expected recurrent infection rate approaching 20%. Further experience with this adjunct may help elucidate its role in the management of this complicated problem, including the need for bead exchanges, until perigraft cultures are free of microbes.

Spontaneous vulvar hematoma during pregnancy: a case report.

BACKGROUND: Vulvar hematoma is a relatively uncommon occurrence. Most have been described resulting from traumatic injury in nonpregnant women or as an uncommon complication of childbirth. We describe a case of a spontaneous 6-cm vulvar hematoma that presented as unexplained vulvar edema in a 35-weeks-pregnant woman. CASE: A pregnant woman presented to the obstetrics triage unit with rapid onset unilateral vulvar swelling and no preceding traumatic event. A detailed physical examination and radiologic evaluation revealed a spontaneous vulvar hematoma as the cause. After incision and drainage of the hematoma, her edema resolved and the patient went on to have an uneventful vaginal delivery 4 weeks later. CONCLUSION: Spontaneous vulvar hematoma is a rare event. Rapid recognition and treatment in this case allowed for complete recovery and enabled this pregnant woman to continue a normal pregnancy with uncomplicated spontaneous vaginal delivery.

Noise exposure levels predict blood levels of the inner ear protein prestin.

Serological biomarkers of inner ear proteins are a promising new approach for studying human hearing. Here, we focus on the serological measurement of prestin, a protein integral to a human's highly sensitive hearing, expressed in cochlear outer hair cells (OHCs). Building from recent nonhuman studies that associated noise-induced OHC trauma with reduced serum prestin levels, and studies suggesting subclinical hearing damage in humans regularly engaging in noisy activities, we investigated the relation between serum prestin levels and environmental noise levels in young adults with normal clinical audiograms. We measured prestin protein levels from circulating blood and collected noise level data multiple times over the course of the experiment using body-worn sound recorders. Results indicate that serum prestin levels have a negative relation with noise exposure: individuals with higher routine noise exposure levels tended to have lower prestin levels. Moreover, when grouping participants based on their risk for a clinically-significant noise-induced hearing loss, we found that prestin levels differed significantly between groups, even though behavioral hearing thresholds were similar. We discuss possible interpretations for our findings including whether lower serum levels may reflect subclinical levels of OHC damage, or possibly an adaptive, protective mechanism in which prestin expression is downregulated in response to loud environments.

A Home-Based Approach to Auditory Brainstem Response Measurement: Proof-of-Concept and Practical Guidelines.

Broad-scale neuroscientific investigations of diverse human populations are difficult to implement. This is because the primary neuroimaging methods (magnetic resonance imaging, electroencephalography [EEG]) historically have not been portable, and participants may be unable or unwilling to travel to test sites. Miniaturization of EEG technologies has now opened the door to neuroscientific fieldwork, allowing for easier access to under-represented populations. Recent efforts to conduct auditory neuroscience outside a laboratory setting are reviewed and then an in-home technique for recording auditory brainstem responses (ABRs) and frequency-following responses (FFRs) in a home setting is introduced. As a proof of concept, we have conducted two in-home electrophysiological studies: one in 27 children aged 6 to 16 years (13 with autism spectrum disorder) and another in 12 young adults aged 18 to 27 years, using portable electrophysiological equipment to record ABRs and FFRs to click and speech stimuli, spanning rural and urban and multiple homes and testers. We validate our fieldwork approach by presenting waveforms and data on latencies and signal-to-noise ratio. Our findings demonstrate the feasibility and utility of home-based ABR/FFR techniques, paving the course for larger fieldwork investigations of populations that are difficult to test or recruit. We conclude this tutorial with practical tips and guidelines for recording ABRs and FFRs in the field and discuss possible clinical and research applications of this approach.

Age-related declines to serum prestin levels in humans.

Measurement of the motor protein prestin offers a novel approach to assessing outer hair cell (OHC) status using serological techniques. Motivated by our prior work showing reduced serum prestin levels in healthy young adults at-risk for noise damage, the current study examined serum prestin levels, measured from circulating blood, across the age span from 18 to 82 years old. Results suggest that serum prestin levels negatively correlate with age, with young adults having higher levels of circulating serum in the blood than older adults. Group-level analyses showed minimal differences in prestin levels between 18 and 29, 30-39, and 40-49 year olds, but significant reductions in the 50+ years-old age group compared to the three younger groups, even though all groups significantly differed from each other in audiometric thresholds and distortion product otoacoustic emissions signal-to-noise ratio. Serum prestin levels declined with increasing levels of hearing loss, with a statistically significant relationship emerging between prestin and low-frequency hearing thresholds (0.25-2 kHz) but a weaker non-significant relationship for high-frequency hearing thresholds (3-8 kHz). This differential pattern between low- and high- frequency thresholds is consistent with the basal-to-apical progression of OHC loss with age. Findings support the idea that serum prestin is the product of residual OHCs in the less age-affected apical regions. Moreover, when entered in a regression model with audiometric thresholds, age was a stronger predictor than pure tone hearing threshold level for predicting serum prestin levels.

Evaluation of two sources of calcium sulfate for a local drug delivery system: a pilot study.

BACKGROUND: Local drug delivery has substantial potential to prevent infections compared with systemic delivery. Although calcium sulfate (CaSO(4)) has been studied for local drug delivery and two types are commercially available, it is unknown whether they differentially release antibiotics. QUESTIONS/PURPOSES: We determined the differences between two sources of CaSO(4) and the K(2)SO(4) catalyst's presence on the degradation, daptomycin elution, and activity against Staphylococcus aureus. METHODS: We formed pellets from synthetic and naturally sourced (from gypsum) CaSO(4) and loaded with 5% daptomycin and 3% or 0% K(2)SO(4). We used in vitro experiments to determine the daptomycin concentration and degradation profiles over 10 days. Turbidity assays were used to evaluate the activity of the daptomycin eluates against S. aureus. RESULTS: All pellets exhibited a bolus release with the highest daptomycin concentration on Day 1 with the sourced CaSO(4) pellets. The synthetic CaSO(4) pellets with 3% K(2)SO(4) exhibited a slower drug release compared with the synthetic CaSO(4) pellets with 0% K(2)SO(4), which degraded and eluted daptomycin too quickly to inhibit S. aureus. Turbidity assays demonstrated that all CaSO(4) pellets inhibit S. aureus for expected lengths of time. CONCLUSIONS: Our preliminary in vitro data suggest differences in the degradation, elution, and activity properties between sourced and synthetic CaSO(4) pellets. The addition of K(2)SO(4) appeared beneficial when using synthetic CaSO(4). Synthetic CaSO(4) may be effective when slow degradation and longer elution times are needed. CLINICAL RELEVANCE: Local delivery of eluted daptomycin can be tailored through material selection and K(2)SO(4) addition.

Comparisons of Auditory Brainstem Responses Between a Laboratory and Simulated Home Environment.

Purpose Miniaturization of digital technologies has created new opportunities for remote health care and neuroscientific fieldwork. The current study assesses comparisons between in-home auditory brainstem response (ABR) recordings and recordings obtained in a traditional lab setting. Method Click-evoked and speech-evoked ABRs were recorded in 12 normal-hearing, young adult participants over three test sessions in (a) a shielded sound booth within a research lab, (b) a simulated home environment, and (c) the research lab once more. The same single-family house was used for all home testing. Results Analyses of ABR latencies, a common clinical metric, showed high repeatability between the home and lab environments across both the click-evoked and speech-evoked ABRs. Like ABR latencies, response consistency and signal-to-noise ratio (SNR) were robust both in the lab and in the home and did not show significant differences between locations, although variability between the home and lab was higher than latencies, with two participants influencing this lower repeatability between locations. Response consistency and SNR also patterned together, with a trend for higher SNRs to pair with more consistent responses in both the home and lab environments. Conclusions Our findings demonstrate the feasibility of obtaining high-quality ABR recordings within a simulated home environment that closely approximate those recorded in a more traditional recording environment. This line of work may open doors to greater accessibility to underserved clinical and research populations.