The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM.

SNAREs provide a large part of the specificity and energy needed for membrane fusion and, to do so, must be localized to their correct membranes. Here, we show that the R-SNAREs VAMP8, VAMP3, and VAMP2, which cycle between the plasma membrane and endosomes, bind directly to the ubiquitously expressed, PtdIns4,5P(2)-binding, endocytic clathrin adaptor CALM/PICALM. X-ray crystallography shows that the N-terminal halves of their SNARE motifs bind the CALM(ANTH) domain as helices in a manner that mimics SNARE complex formation. Mutation of residues in the CALM:SNARE interface inhibits binding in vitro and prevents R-SNARE endocytosis in vivo. Thus, CALM:R-SNARE interactions ensure that R-SNAREs, required for the fusion of endocytic clathrin-coated vesicles with endosomes and also for subsequent postendosomal trafficking, are sorted into endocytic vesicles. CALM's role in directing the endocytosis of small R-SNAREs may provide insight into the association of CALM/PICALM mutations with growth retardation, cognitive defects, and Alzheimer's disease.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Opening Access but Concealing Contact: A First Study of Over-The-Counter Hearing Aid Consumer-Facing Communications.

Hearing loss is a prevalent chronic health condition with approximately 40 million Americans living with mild to moderate hearing loss. Yet, only about 20% will ever pursue hearing interventions. To broaden uptake the FDA approved over the counter (OTC) hearing aid (HA) options in October 2022. A stigmatized health topic, it is both necessary and well-timed to explore how HAs are depicted in consumer-facing communications, which has not been formally studied to date. The present study examines social media posts across a one-year time frame (six months prior and six months following the FDA announcement) from the three most-followed OTC HA brands. With the shift to OTC, HA companies are responsible for communicating directly with consumers. Through the lens of Contact Theory, we explore three mechanisms by which these messages enact stigma, through contact with (1) people, (2) HA products, and (3) a larger brand community. Overall, only 22% of posts discussed OTC in any capacity. Contact was similarly limited, with only 9% of posts showing a person wearing an HA. However, following the FDA announcement, the number of posts depicting people or social relationships doubled (23% to 58% and 13% to 36%, respectively). To overcome stigma and increase uptake of these essential health products, it is important to promote contact with hearing aids and those who wear them. Timely implications for health communication research and practice are discussed.

Immersion Experiences for Biomedical Engineering Undergraduates: Comparing Strategies and Local Partnerships at Two Institutions.

Immersion experiences for undergraduate students in biomedical engineering are key contributors to their ability to identify medical needs. Despite this, as few as 25% of surveyed programs report providing such opportunities. Since 2010 when the National Institute of Health began its R25 grant mechanism to support curricular development toward team-based design, several institutions have established programs for immersion experiences, which provide precedent for their implementation. Published results from such immersion experiences highlight successes in structure and changes in student perspectives after these experiences. As more institutions expand their biomedical engineering curriculum with new immersion-focused programs, it is important to learn from these precedents while also considering opportunities to improve. For newly funded groups that are developing and implementing programs, they may find improved success by strategic use of unique partnerships. However, these partnerships may not be immediately evident to program organizers. Our objective is to discuss two institutions that recently established programs for immersion experience. In the comparison of our two immersion programs, we found five overlapping core features that include: immersion partner collaboration, team-based immersion experiences, needs-finding emphasis, team-based engineering design experiences, and immersion assessment and evaluation. Both programs developed collaborative partnerships with nearby medical schools. Additionally, one program partnered with a community resource (i.e., Human Development Institute). Despite nuanced program differences, we found that students at both programs self-reported increased knowledge or confidence in aspects of the design process (e.g., identifying and refining user needs, concept generation). Our results also highlight student gains unique to their programs - UK students self-reported gains on disability topics and IUPUI students self-reported gains on socioeconomic awareness. In summary, immersion partner collaboration, or partnership, surfaced as a core feature for both programs, and students in both immersion programs endorsed enhanced knowledge or confidence in engineering design.

A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma.

BACKGROUND: Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM. METHODS: Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored. RESULTS: The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK. CONCLUSIONS: With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Part 1- NCT01812603; Part 2- NCT01812616.

Finite Element Analysis as an Iterative Design Tool for Students in an Introductory Biomechanics Course.

Insufficient engineering analysis is a common weakness of student capstone design projects. Efforts made earlier in a curriculum to introduce analysis techniques should improve student confidence in applying these important skills toward design. To address student shortcomings in design, we implemented a new design project assignment for second-year undergraduate biomedical engineering students. The project involves the iterative design of a fracture fixation plate and is part of a broader effort to integrate relevant hands-on projects throughout our curriculum. Students are tasked with (1) using computer-aided design (CAD) software to make design changes to a fixation plate, (2) creating and executing finite element models to assess performance after each change, (3) iterating through three design changes, and (4) performing mechanical testing of the final device to verify model results. Quantitative and qualitative methods were used to assess student knowledge, confidence, and achievement in design. Students exhibited design knowledge gains and cognizance of prior coursework knowledge integration into their designs. Further, student's self-reported confidence gains in approaching design, working with hardware and software, and communicating results. Finally, student self-assessments exceeded instructor assessment of student design reports, indicating that students have significant room for growth as they progress through the curriculum. Beyond the gains observed in design knowledge, confidence, and achievement, the fracture fixation project described here builds student experience with CAD, finite element analysis, three-dimensional printing, mechanical testing, and design communication. These skills contribute to the growing toolbox that students ultimately bring to capstone design.

Psychiatric mental health nursing in the international year of the nurse and COVID-19: One hospital's perspective on resilience and innovation - Past, present and future.

In the International Year of the Nurse, we are in the midst of a global pandemic. Historically, nurses have been at the forefront of crises influencing standards of care and public health policy. Managing psychiatric patients during the current COVID-19 pandemic has challenged the psychiatric nurses' role within the therapeutic milieu fostering innovative practices to meet patient needs. Our behavioral health center met the challenges with resilience, creativity and commitment. The next challenge is to learn from experience. Building on innovative technology opens the window to new models of care. Understanding resilience is critical to preparing for the next crisis.

Suboptimal UVA attenuation by broad spectrum sunscreens under outdoor solar conditions contributes to lifetime UVA burden.

BACKGROUND: Broad spectrum sunscreens with a sun protection factor (SPF) of 15 or greater are indicated to decrease the risk of skin cancer and early skin aging caused by the sun if used as directed with other sun protection measures. To determine whether sunscreen product performance is compromised under solar exposure and to test spectral uniformity of protection across the UVA spectrum, we tested broad spectrum sunscreens with a variety of active pharmaceutical ingredients (APIs) and in a variety of dosage forms. METHODS: A cross-sectional market survey of 32 sunscreen drug products containing either organic or inorganic APIs with SPFs of 15, 30, 50, and 70 was tested. UV doses were delivered via natural sun in Silver Spring, Maryland between June and September of 2017. RESULTS: Of the 32 sunscreen drug products, 6 products failed to meet their broad spectrum claim under solar exposure. Using FDA's new proposal to strengthen sunscreen broad spectrum requirements, spectral uniformity based on the mean sunscreen absorbance of UVA1(340-400 nm)/UV (290-400 nm) indicated that ~40% of sunscreen drug products tested had suboptimal UVA protection. CONCLUSION: US consumers may unknowingly be receiving up to 36% more transmitted UVA when selecting between similarly labeled broad spectrum sunscreen drug products with equivalent SPF values. FDA's new proposal may help decrease consumers' overall lifetime UVA burden. Spectral absorbance data on sunscreen performance can be used to further improve the coupling of broad spectrum protection to a product's SPF value so that consumers have improved proportional increases in UV protection.

Use of puppets to teach resourcefulness skills to women who self-injure: An exploratory study.

BACKGROUND: Self-injurious behavior (SIB), when frequent and repetitive, can lead to risk behaviors resulting in accidental or intentional suicide. Psychoeducation about resourcefulness can be critical to interrupt the cycle of self-injury. Therapeutic puppetry provides a safe and secure vehicle for expressing feelings without fear of retaliation. OBJECTIVES: Determine the outcome of a resourcefulness psychoeducation program, utilizing hand puppets as a teaching tool, on the measure of resourcefulness for adult women who self-injure. METHODS: A psychoeducation program, utilizing hand puppets as a teaching tool, was offered to women during psychiatric hospitalization. Participants completed the Resourcefulness Scale (RS) pre and post intervention. A program evaluation to determine the effectiveness of hand puppets was completed. Acceptability and feasibility of the program was evaluated. RESULTS: Sixteen participants completed the program. Results showed a statistically insignificant increase in scores. The program evaluation revealed agreement that resourcefulness learning was accomplished. Participants reported that hand puppets were helpful in practicing resourcefulness skills. Majority of participants recommended continuation of the program.

UV exposure modulates hemidesmosome plasticity, contributing to long-term pigmentation in human skin.

Human skin colour, ie pigmentation, differs widely among individuals, as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals, UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, eg solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA + UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from six healthy individuals (three LLP+ and three LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA + UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighbouring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin α6ß4 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin colour. These results suggest that the hyperpigmentation phenomenon leading to increased interdigitation develops in order to maintain normal skin homeostasis in individuals with LLP.

Neural Correlates of Phonetic Learning in Postlingually Deafened Cochlear Implant Listeners.

OBJECTIVE: The present training study aimed to examine the fine-scale behavioral and neural correlates of phonetic learning in adult postlingually deafened cochlear implant (CI) listeners. The study investigated whether high variability identification training improved phonetic categorization of the /ba/-/da/ and /wa/-/ja/ speech contrasts and whether any training-related improvements in phonetic perception were correlated with neural markers associated with phonetic learning. It was hypothesized that training would sharpen phonetic boundaries for the speech contrasts and that changes in behavioral sensitivity would be associated with enhanced mismatch negativity (MMN) responses to stimuli that cross a phonetic boundary relative to MMN responses evoked using stimuli from the same phonetic category. DESIGN: A computer-based training program was developed that featured multitalker variability and adaptive listening. The program was designed to help CI listeners attend to the important second formant transition cue that categorizes the /ba/-/da/ and /wa/-/ja/ contrasts. Nine adult CI listeners completed the training and 4 additional CI listeners that did not undergo training were included to assess effects of procedural learning. Behavioral pre-post tests consisted of identification and discrimination of the synthetic /ba/-/da/ and /wa/-/ja/ speech continua. The electrophysiologic MMN response elicited by an across phoneme category pair and a within phoneme category pair that differed by an acoustically equivalent amount was derived at pre-post test intervals for each speech contrast as well. RESULTS: Training significantly enhanced behavioral sensitivity across the phonetic boundary and significantly altered labeling of the stimuli along the /ba/-/da/ continuum. While training only slightly altered identification and discrimination of the /wa/-/ja/ continuum, trained CI listeners categorized the /wa/-/ja/ contrast more efficiently than the /ba/-/da/ contrast across pre-post test sessions. Consistent with behavioral results, pre-post EEG measures showed the MMN amplitude to the across phoneme category pair significantly increased with training for both the /ba/-/da/ and /wa/-/ja/ contrasts, but the MMN was unchanged with training for the corresponding within phoneme category pairs. Significant brain-behavior correlations were observed between changes in the MMN amplitude evoked by across category phoneme stimuli and changes in the slope of identification functions for the trained listeners for both speech contrasts. CONCLUSIONS: The brain and behavior data of the present study provide evidence that substantial neural plasticity for phonetic learning in adult postlingually deafened CI listeners can be induced by high variability identification training. These findings have potential clinical implications related to the aural rehabilitation process following receipt of a CI device.

Prescription opioid use: Patient characteristics and misuse in community pharmacy.

OBJECTIVES: Opioid pain medication misuse is a major concern for US public health. The purpose of this article is to: 1) describe the demographic and physical, behavioral, and mental health characteristics of patients who fill opioid medications in community pharmacy settings; and 2) describe the extent of opioid medication misuse behaviors among these patients. DESIGN: We recruited and screened a convenience sample of patients with the use of a tablet computer-based assessment protocol that examined behavioral, mental, and physical health. Descriptive and inferential statistics were calculated to describe respondents and their opioid medication misuse and health characteristics. SETTING: Patients were screened in 2 urban and 2 rural community pharmacies in southwestern Pennsylvania. PARTICIPANTS: Survey participants were adult patients filling opioid pain medications who were not currently receiving treatment for a cancer diagnosis. INTERVENTION: None. MAIN OUTCOME MEASURES: Validated screening measures included the Prescription Opioid Misuse Index, Alcohol Use Disorders Identification Test C, Short Form 12, Drug Abuse Screening Test 10, Primary Care Post-traumatic Stress Disorder (PTSD) screen, and the Patient Health Questionnaire 2. RESULTS: A total of 333 patients were screened (71.2% response rate). Nearly the entire population reported pain above and general health below national norms. Hydrocodone (19.2%) and morphine (20.8%) were found to be the medications with the highest rates of misuse-with hydrocodone having more than 4 times higher odds of misuse compared with other medications (adjusted odds ratio [AOR] 4.48, 95% confidence interval [CI] 1.1-17.4). Patients with positive screens for illicit drug use (AOR 8.07, 95% CI 2.7-24.0), PTSD (AOR 5.88, 95% CI 2.3-14.7), and depression (AOR 2.44, 95% CI 1.0-5.9) also had significantly higher odds for misuse compared with those with negative screening results. CONCLUSION: These findings provide important foundational data that suggest implementation of regular opioid misuse screening protocols within community pharmacies. Such screening activities could foster a culture of prevention and overall reduction for misuse among patients filling opioid medications in community pharmacies.

Novel missense MTTP gene mutations causing abetalipoproteinemia.

OBJECTIVE: The microsomal triglyceride transfer protein (MTTP) plays a critical role in the formation of hepatic very low density lipoprotein. Abetalipoproteinemia (ABL) is a rare, naturally occurring extreme form of MTTP inhibition, which is characterized by the virtual absence of apolipoprotein (apo) B-containing lipoproteins in blood. The goal of this study was to examine the effect that four novel MTTP missense mutations had on protein interactions, expression and lipid-transfer activity, and to determine which mutations were responsible for the ABL phenotype observed in two patients. APPROACH AND RESULTS: In two patients with ABL, we identified in MTTP a novel frameshift mutation (K35Ffs*37), and four novel missense mutations, namely, G264R, Y528H, R540C, and N649S. When transiently expressed in COS-7 cells, all missense MTTP mutations interacted with apoB17, apoB48, and protein disulfide isomerase. Mutations Y528H and R540C, however, displayed negligible levels of MTTP activity and N649S displayed a partial reduction relative to the wild-type MTTP. In contrast, G264R retained full lipid-transfer activity. CONCLUSIONS: These studies indicate that missense mutations Y528H, R540C, and N649S appear to cause ABL by reducing MTTP activity rather than by reducing binding of MTTP with protein disulfide isomerase or apoB. The region of MTTP containing amino acids 528 and 540 constitutes a critical domain for its lipid-transfer activity.

Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry.

Differences in visible skin pigmentation give rise to the wide variation of skin colours seen in racial/ethnic populations. Skin pigmentation is important not only from cosmetic and psychological points of view, but more importantly because of its implications for the risk of all types of skin cancers, on photoaging, etc. Despite differences in those parameters in Caucasian and Asian skin types, they are remarkably similar in their production and distribution of melanins, and the mechanism(s) underlying their different characteristics have remained obscure. In this study, we used microarray analysis of skin suction blisters to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Intriguingly, Caucasian and Asian skins had highly similar gene expression patterns that differed significantly from the pattern of African skin. The results of this study suggest the dynamic interactions of different types of cells in human skin that regulate its pigmentation, reveal that the known pigmentation genes have a limited contribution and uncover a new array of genes, including NINL and S100A4, that might be involved in that regulation.

Dual-functioning phage-derived peptides encourage human bone marrow cell-specific attachment to mineralized biomaterials.

Cell instructive mineralized biomaterials are a promising alternative to conventional auto-, allo-, and xenograft therapies for the reconstruction of critical sized defects. Extracellular matrix proteins, peptide domains, and functional motifs demonstrating cell and mineral binding activity have been used to improve cell attachment. However, these strategies vary in their tissue regeneration outcomes due to lack of specificity to both regenerative cell populations and the material substrates. In order to mediate cell-specific interactions on apatite surfaces, we identified peptide sequences with high affinity towards apatite (VTKHLNQISQSY, VTK) and clonally derived human bone marrow stromal cells (DPIYALSWSGMA, DPI) using phage display. The primary aims of this study were to measure apatite binding affinity, human bone marrow stromal cell (hBMSC) adhesion strength, and peptide specificity to hBMSCs when the apatite and cell-specific peptides are combined into a dual-functioning peptide. To assess binding affinity to hydroxyapatite (HA), binding isotherms were constructed and peptide binding affinity (K1) determined. HBMSC, MC3T3 and mouse dermal fibroblast (MDF) adhesion strength on biomimetic apatite functionalized with single- and dual-functioning peptide sequences were evaluated using a centrifugation assay. DPI-VTK had the highest binding strength towards hBMSCs (p < 0.01). DPI-VTK, while promoting strong initial attachment to hBMSCs, did not encourage strong adhesions to MC3T3s or fibroblasts (p < 0.01). Taken together, phage display is a promising strategy to identify preferential cell and material binding peptide sequences that can tether specific cell populations onto specific biomaterial chemistries.

Neural coding of phonemic fricative contrast with and without hearing aid.

OBJECTIVE: To determine whether auditory event-related potentials (ERPs) to a phonemic fricative contrast ("s" and "sh") show significant differences in listening conditions with or without a hearing aid and whether the aided condition significantly alters a listener's ERP responses to the fricative speech sounds. DESIGN: The raw EEG data were collected using a 64-channel system from 10 healthy adult subjects with normal hearing. The fricative stimuli were digitally edited versions of naturally produced syllables, /sa/ and /∫a/. The evoked responses were derived in unaided and aided conditions by using an alternating block design with a passive listening task. Peak latencies and amplitudes of the P1-N1-P2 components and the N1' and P2'' peaks of the acoustic change complex (ACC) were analyzed. RESULTS: The evoked N1 and N1' responses to the fricative sounds significantly differed in the unaided condition. The fricative contrast also elicited distinct N1-P2 responses in the aided condition. While the aided condition increased and delayed the N1 and ACC responses, significant differences in the P1-N1-P2 and ACC components were still observed, which would support fricative contrast perception at the cortical level. CONCLUSION: Despite significant alterations in the ERP responses by the aided condition, normal-hearing adult listeners showed distinct neural coding patterns for the voiceless fricative contrast, "s" and "sh," with or without a hearing aid.

In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide.

OBJECTIVE: To demonstrate a near-infrared (NIR) peptide that is highly specific for colonic adenomas on fluorescence endoscopy in vivo. DESIGN: A 3 mm diameter endoscope was adapted to deliver 671 nm illumination and collect NIR fluorescence (696-736 nm). Target (QPIHPNNM) and control (YTTNKH) peptides were labelled with Cy5.5, a NIR dye, and characterised by mass spectra. The peptides were topically administered separately (100 µM) through the endoscope's instrument channel into the distal colon of CPC;Apc mice, genetically engineered to spontaneously develop adenomas. After 5 min for incubation, the unbound peptides were rinsed off, and images were collected at a rate of 10 frames/s. Regions of interest were identified around the adenoma and adjacent normal-appearing mucosa on white light. Intensity measurements were made from these same regions on fluorescence, and the target-to-background ratio (TBR) was calculated. RESULTS: An image resolution of 9.8 µm and field of view of 3.6 mm was achieved at a distance of 2.5 mm between the distal end of the instrument and the tissue surface. On mass spectra, the experimental mass-to-charge ratio for the Cy5.5-labelled target and control peptides agreed with expected values. The NIR fluorescence images of adenomas revealed individual dysplastic crypts with distorted morphology. By comparison, only amorphous surface features could be visualised from reflected NIR light. The average TBR for adenomas was found to be 3.42 ± 1.30 and 1.88 ± 0.38 for the target and control peptides, respectively, p=0.007. CONCLUSION: A NIR peptide was shown to be highly specific for colonic adenomas on fluorescence endoscopy in vivo and to achieve sub-cellular resolution images.

A Qualitative Study of Biomedical Engineering Student Critical Reflection During Clinical Immersion Experiences.

Purpose: Clinical immersion experiences provide engineering students with opportunities to identify unmet user needs and to interact with clinical professionals. These experiences have become common features of undergraduate biomedical engineering curricula, with many published examples in the literature. There are, however, few or no published studies that describe rigorous qualitative analysis of biomedical engineering student reflections from immersion programs. Methods: Fifteen reflection prompts that align with program learning goals were developed and structured based on the DEAL model for critical reflection. Undergraduate participants in a summer immersion program responded to these prompts throughout five weeks of clinical rotations. Data from two summer cohorts of participants (n = 20) were collected, and thematic analysis was performed to characterize student responses. Results: Students reported learning about key healthcare topics, such as medical insurance, access to healthcare (and lack thereof), stakeholder perspectives, and key medical terminology and knowledge. Most reflections also noted that students could apply newly gained medical knowledge to biomedical engineering design. Further, clinical immersion provided students with a realistic view of the biomedical engineering profession and potential areas for future professional growth, with many reflections identifying the ability to communicate with a variety of professionals as key to student training. Some students reflected on conversations with patients, noting that these interactions reinvigorated their passion for the biomedical engineering field. Finally, 63% of student reflections identified instances in which patients of low socioeconomic status were disadvantaged in health care settings. Conclusions: Clinical immersion programs can help close the gap between academic learning and the practical experience demands of the field, as design skills and product development experience are becoming increasingly necessary for biomedical engineers. Our work initiates efforts toward more rigorous analysis of students' reactions and experiences, particularly around socioeconomic and demographic factors, which may provide guidance for continuous improvement and development of clinical experiences for biomedical engineers.

Electrophysiological auditory measures to identify potential cortical markers of tinnitus.

Tinnitus, or the perception of a sound in the absence of an external acoustic stimulus, is a common condition that cannot yet be objectively diagnosed. Current diagnostic tests of tinnitus consist of case history and behavioral measures that rely on subjective responses. This study examined electrophysiological measures, specifically the auditory late response (ALR), mismatch negativity (MMN), and P300 as potential neural biomarkers of tinnitus in both a tinnitus and non-tinnitus control group while utilizing the pitch-matched tinnitus frequencies as the test stimuli. Results of this study found differences in MMN amplitudes and area under the curve, and in P300 topographic maps between tinnitus and control subjects. The differences in MMN responses across groups suggest that dysfunctional processing of acoustic stimuli located near the tinnitus frequency in individuals with tinnitus manifests as soon as 200 ms after initial onset of the stimulus. In addition, results from a global field power analysis and differences in spatial distributions on topographical maps indicate that deficits persist through higher levels of cortical processing. A secondary goal of this study was to determine if electrophysiological measures correlated with reported tinnitus severity on questionnaires. This analysis indicated that P2 latency was a significant predictor of Tinnitus Reaction Questionnaire, Tinnitus Handicap Inventory, and percent of the time participant's tinnitus was considered bothersome, suggesting that this measure could potentially be used to assess the efficacy of treatment programs for tinnitus.