Identifying an acceptable number of ambulatory blood pressure measurements for accuracy of average blood pressure and nocturnal dipping status.

We aimed to identify the minimum number of ambulatory blood pressure (ABP) measures to accurately determine daytime and nighttime systolic blood pressure (BP) averages and nocturnal dipping status (i.e., relative daytime:nighttime change). A total of 43 midlife participants wore an ABP monitor for 24 h with measurements every 20/30 min during the daytime/nighttime, as identified by a sleep diary. We calculated daytime/nighttime systolic BP average and dipping status from all available measurements per participant (i.e., normative data). We then calculated daytime and nighttime BP per participant based on a random selection of 8-20 and 4-10 measurements and replicated random selections 1,000 times. We calculated accuracy by checking the proportion from 1,000 different randomly selected samples for a particular number of measurements that systolic BP was ±5 mmHg of normative data, and dipping status remained unchanged for each participant compared with the normative value. The best fit for the regression model estimated the minimal number of measurements for an accuracy of 95% in BP averages. For a 95% accuracy in estimating daytime and nighttime systolic BP, 11 daytime and 8 nighttime measurements were required. The highest accuracy for dipping status was 91.6 ± 13.4% using 20 daytime and 10 nighttime measures, while the lowest was (83.4 ± 15.1%) using 8 daytime and 4 nighttime measures. In midlife adults, 11 daytime and 8 nighttime measurements are likely enough to calculate average systolic BPs accurately. However, no minimum number is suggested to accurately calculate dipping status.NEW & NOTEWORTHY We found that a minimum of 11 blood pressure (BP) measures are necessary to calculate an accurate average daytime BP, and 8 nighttime measures are necessary to calculate an accurate nighttime average if 95% accuracy is acceptable. Regarding BP dipping status, the current recommendations (20 daytime/7 nighttime) inaccurately classified the dipping status 10.5% of the time, suggesting that guidelines may need to be updated to classify patients as nocturnal dippers or nondippers correctly.

Chronological distribution of readings in ambulatory blood pressure monitoring exams affects the nighttime average and the magnitude of blood pressure dipping.

STUDY OBJECTIVES: Averaged nighttime blood pressure (BP) is superior to daytime BP for cardiovascular risk stratification, and the relative change between daytime/nighttime BP (dipping%) significantly predicts cardiovascular risk. Newer reports suggest that 4 measurements at night may be enough for cardiovascular risk stratification. Since BP oscillates across the night, the temporal distribution of measurements across the night may impact nighttime BP and dipping%. Therefore, we compared average nighttime BP and dipping% when using measurements in the first half (1st-half), second (2nd-half), and a combination of both (combined). METHODS: Forty-three (17 females and twenty-six males) midlife adults aged 50±10 years old wore an ambulatory BP monitor for 24 hours at home, programmed to measure BP every 20 minutes when scheduled for daytime and every 30 minutes during a self-selected 8-hour nighttime for time-in-bed. We compared the nighttime BP averages and dipping% when using either the first four measurements from the 1st-half or 2nd-half of the nighttime and combined. RESULTS: Nighttime Systolic BP was significantly different across 1st-half, 2nd-half, and combined (111±9 vs.107±11 vs. 109±9 mmHg, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each). Systolic BP dipping% was significantly different across 1st-half, 2nd-half, and combined (9.9±5.5 vs.13.5±6.4 vs. 11.7±5.0 %, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each. Diastolic BP and diastolic dipping% were similar across the three different bins. CONCLUSION: In midlife adults, systolic nighttime BP and dipping% may depend upon when BP measurements are taken during the night.

Hypocalcemia in Trauma is Determined by the Number of Units Transfused, Not Whole Blood Versus Component Therapy.

INTRODUCTION: Blood component resuscitation is associated with hypocalcemia (HC) (iCal <0.9 mmol/L) that contributes to coagulopathy and death in trauma patients. It is unknown whether or not whole blood (WB) resuscitation helps mitigate the risk of HC in trauma patients. We hypothesized that calcium homeostasis is maintained and mortality improved in patients who only receive WB. MATERIALS AND METHODS: This is a retrospective review of all adult trauma patients who received WB from July 2018 to December 2020. Variables included transfusions, ionized calcium levels, and calcium replacement. Patients were characterized as follows based on blood products received: WB or WB with other blood components. Groups were compared with respect to HC, correction of HC, 24 h, and inpatient mortality. RESULTS: Two hundred twenty-three patients received WB and met the inclusion criteria. 107 (48%) received WB only. HC occurred in 13% of patients who received more than one WB unit compared to 29% of WB and other blood component patients (P = 0.02). WB patients received less calcium replacement (median 250 mg versus 2000 mg, P < 0.01). HC and total units transfused within 4 h were associated with mortality in the adjusted model. HC significantly increased after 5 units of blood products were transfused, regardless of product type. WB was not protective against HC. CONCLUSIONS: HC and failure to correct HC are significant risk factors for mortality in trauma. Resuscitations with WB only and WB in combination with other blood components are associated with HC especially when more than 5 units of any blood product are transfused. Calcium supplementation should be prioritized in any large volume transfusion, regardless of blood product type.

A Prospective, Multicenter Trial on the Efficacy and Safety of Poly-L-Lactic Acid for the Treatment of Contour Deformities of the Buttock Regions.

BACKGROUND: There is a significant emphasis on minimally invasive whole-body rejuvenation throughout the world. Recently, gluteal aesthetics have become an increasingly common patient concern. Although the application of poly-L-lactic acid (PLLA) to the face is already well known, there are relatively fewer publications on its use in other corporeal regions. This study aims to extend previous findings by evaluating the efficacy and safety of PLLA in the treatment of contour (including lifting) deformities of the buttock region. METHODS: This was a prospective, multicenter (3 sites), single cohort, open-label clinical trial. Thirty female subjects were treated with PLLA in the bilateral buttocks, with three treatment sessions, each spaced one month apart and followed for six months after completion of the treatment regimen. At each visit, various safety and clinical efficacy parameters were collected, these included: Global Assessment of Improvement Scale (GAIS), subject satisfaction, skin hydration, elasticity, scaliness, roughness, and 3-dimensional imagery. RESULTS: Six months following the last treatment, 84.00% of patients were rated as having “improved” or more on the physician assessed GAIS, accompanied by a 96.00% patient satisfaction rate. Approximately three vials of PLLA, per buttock and treatment were used. There were no serious adverse events throughout the duration of the trial, nor adverse events related to the investigational device. The most common subject-reported adverse events included pain during treatment (Mean: 70.97%) and bruising (Mean: 28.80%). Objective improvements were persistent after treatment in measurements of skin elasticity (improved 63.5% - 82.5% from weeks 16-32), hydration (increased ~11 Corneometer® units by week 16), roughness (decreased 36.95% at week 32), and scaliness (desquamation; decreased 60.41% at week 32). CONCLUSIONS: PLLA is safe and effective for the indication of buttock contouring and improving parameters of skin health. PLLA can provide long-lasting effects with a high level of patient and physician satisfaction. J Drugs Dermatol. 2022;21(3):304-308. doi:10.36849/JDD.5924.

Expert Recommendations on the Use of Injectable Poly-L-lactic Acid for Contour Deficiencies of the Buttocks.

Poly-L-lactic acid (PLLA) is an injectable biodegradable biostimulator that promotes collagen production and is approved for use in aesthetic facial augmentation. PLLA is well tolerated with minimal downtime and has demonstrated an excellent safety profile, as well as a longevity benefit of at least 2 years following injection. The robust safety and efficacy profile associated with PLLA for facial rejuvenation has resulted in a growing interest in the use of PLLA for other body areas such as the buttocks, which are an increasingly popular target of aesthetic enhancement. Patient goals for gluteal enhancement include improving contour and texture, reduction in visible cellulite and increased volume and lift. In order to achieve optimal outcomes and patient satisfaction, it is essential to ensure correct usage of PLLA; however, there is currently a lack of guidelines and expert recommendations in this area. This report reflects consensus recommendations for the use of PLLA in non-invasive buttock contouring, including patient selection, PLLA preparation, dosing, injection and, efficacy and safety assessments. Recommendations were provided by the collective author group, comprising international leaders in the field of aesthetics, dermatology, and plastic surgery. J Drugs Dermatol. 2022;21(1):21-26. doi:10.36849/JDD.6180.

Cross-Cultural Measurement of Positive and Negative Emotions in Adolescence: Evidence from Three Countries.

Cross-cultural assessment of affective well-being among adolescents has received scarce attention in positive psychological research. The present study investigated cross-cultural measurement invariance of the Scale of Positive and Negative Experience (SPANE) among adolescents from three countries (India, Poland, and Serbia). The sample included a total of 1080 adolescents (53.6% female; M age = 16.75, range = 15-19 years). Surveys were administered online in each country. Measurement invariance testing provided evidence for partial scalar invariance of the SPANE across cultures, with item "afraid" showing nonivariance across the three countries. Latent factor correlations between positive and negative emotions were stronger in Serbia compared to Poland and India. Positive emotions and life satisfaction had strong positive associations in all three countries (ranging from 0.68 to 0.75). The inverse correlations between negative emotions and life satisfaction were - 0.27, - 0.54, - 0.69 in India, Poland, and Serbia, respectively. Polish adolescents demonstrated the lowest levels of affective well-being, whereas Indian and Serbian adolescents did not differ substantially in levels of positive and negative emotions. The present study demonstrated that the SPANE is a reliable and useful tool for the assessment of positive and negative emotions among adolescents from different cultural settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-022-00521-6.

Exploring biopsychosocial correlates of pain, pain management strategies, and risk for opioid misuse among home care workers in Washington State.

Home care workers (HCWs) are at high risk for musculoskeletal pain and injury, and they are an important population for pain management research and intervention. The purpose of this study was to gather novel data on HCWs' work characteristics, pain experiences, pain management strategies, and risk for opioid misuse. A survey invitation was e-mailed to a random sub-sample of HCWs in Washington State, and 421 responded. Over half (54.2%) reported chronic or currently elevated pain. Pharmacological pain management strategies were used by 67.3% of all respondents with 4.8% reporting prescription opioid use. Biopsychosocial factors like injuries, interpersonal conflict, financial strain, and anxiety were associated with increased opioid misuse risk. Multimodal primary and secondary interventions are recommended to improve HCWs' pain management.

Video on Diet Before Outpatient Colonoscopy Does Not Improve Quality of Bowel Preparation: A Prospective, Randomized, Controlled Trial.

OBJECTIVES: Successful outpatient colonoscopy (CLS) depends on many factors including the quality of a patient's bowel preparation. Although education on consumption of the pre-CLS purgative can improve bowel preparation quality, no study has evaluated dietary education alone. We have created an educational video on pre-CLS dietary instructions to determine whether dietary education would improve outpatient bowel preparation quality. METHODS: A prospective randomized, blinded, controlled study of patients undergoing outpatient CLS was performed. All patients received a 4 l polyethylene glycol-based split-dose bowel preparation and standard institutional pre-procedure instructions. Patients were then randomly assigned to an intervention arm or to a no intervention arm. A 4-min educational video detailing clear liquid diet restriction was made available to patients in the intervention arm, whereas those randomized to no intervention did not have access to the video. Patients randomized to the video were provided with the YouTube video link 48-72 h before CLS. An attending endoscopist blinded to randomization performed the CLS. Bowel preparation quality was scored using the Boston Bowel Preparation Scale (BBPS). Adequate preparation was defined as a BBPS total score of ≥6 with all segment scores ≥2. Wilcoxon rank-sum and Pearson's χ2-tests were performed to assess differences between groups. RESULTS: Ninety-two patients were randomized (video: n=42; control: n=50) with 47 total video views being tallied. There were no demographic differences between groups. There was no statistically significant difference in adequate preparation between groups (video=74%; control=68%; P=0.54). CONCLUSIONS: The availability of a supplementary patient educational video on clear liquid diet alone was insufficient to improve bowel preparation quality when compared with standard pre-procedure instruction at our institution.

Transitioning to Working from Home Due to the COVID-19 Pandemic Significantly Increased Sedentary Behavior and Decreased Physical Activity: A Meta-Analysis.

At the start of the COVID-19 pandemic, many workplaces transitioned to remote work, which altered lifestyle behaviors. We conducted a meta-analysis to understand if the transition to working from home due to the pandemic affected workers' physical activity and sedentary behavior worldwide. We reviewed articles published between November 2019 and May 2022. Of an initial 3485 articles, a total of 17 were included, 15 of 17 were included for their physical activity (PA) comparisons (n = 36,650), and 12 of 17 (n = 57,254) were included for their sedentary behavior (SB) comparisons (10 studies have data for both PA and SB). This work is registered through PROSPERO (CRD42022356000). Working from home resulted in a significant decrease in PA (Hedge's g = -0.29, 95% CI [-0.41, -0.18]) and an increase in SB (Hedge's g = +0.36, 95% CI [0.20, 0.52]). Working from home impaired preventative activity behaviors, and these results are relevant to worker health as the future of work evolves beyond the pandemic.

Circadian alignment, cardiometabolic disease, and sex specific differences in adults with overweight/obesity.

OBJECTIVE: Circadian disruption promotes weight gain and poor health. The extent to which sex plays a role in the relationship between the circadian timing of behaviors and health outcomes in individuals with overweight/obesity is unclear. We investigated the sex-specific associations between circadian alignment and cardiometabolic health markers in females and males with overweight/obesity. METHODS: Thirty volunteers with overweight/obesity (15 female; BMI≥25.1kg/m2) underwent an evening in-laboratory assessment for dim-light melatonin onset (DLMO), body composition via dual energy x-ray absorptiometry, and a fasted blood sample. Circadian alignment was determined as the time difference between DLMO and average sleep onset over 7-days (phase angle), with participants categorized into narrow/wide phase angle groups based on median phase angle split. Due to known differences in metabolic markers between sexes, participants were subdivided based on sex into narrow and wide phase angle groups. RESULTS: Males in the narrow phase angle group had higher android/gynoid body fat distribution, triglycerides, and Metabolic Syndrome risk scores, while females had higher overall body fat percentage, glucose, and resting heart rates (all p<0.04). Furthermore, a narrower phase angle in males was negatively associated with android/gynoid body fat (r=-0.53, p=0.04) and negatively associated with body fat (r=-0.62, p=0.01) and heart rate (r=-0.73, p<0.01) in females. CONCLUSION: Circadian disruption may not only promote a trajectory of weight gain but could also contribute to negative health consequences in a sex-dependent manner in those already with overweight/obesity. These data may have implications for clinical utility in sex-specific sleep and circadian interventions for adults with overweight/obesity.

Frequencies and spectra of aflatoxin B1-induced mutations in liver genomes of NEIL1-deficient mice as revealed by duplex sequencing.

Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary exposures to foods contaminated with aflatoxin-producing molds. Intracellular metabolic activation of aflatoxin B1 (AFB1) to a reactive epoxide generates highly mutagenic AFB1-Fapy-dG adducts. Previously, we demonstrated that repair of AFB1-Fapy-dG adducts can be initiated by the DNA glycosylase NEIL1 and that male Neil1-/- mice were significantly more susceptible to AFB1-induced HCC relative to wild-type mice. To investigate the mechanisms underlying this enhanced carcinogenesis, WT and Neil1-/- mice were challenged with a single, 4 mg/kg dose of AFB1 and frequencies and spectra of mutations were analyzed in liver DNAs 2.5 months post-injection using duplex sequencing. The analyses of DNAs from AFB1-challenged mice revealed highly elevated mutation frequencies in the nuclear genomes of both males and females, but not the mitochondrial genomes. In both WT and Neil1-/- mice, mutation spectra were highly similar to the AFB1-specific COSMIC signature SBS24. Relative to wild-type, the NEIL1 deficiency increased AFB1-induced mutagenesis with concomitant elevated HCCs in male Neil1-/- mice. Our data establish a critical role of NEIL1 in limiting AFB1-induced mutagenesis and ultimately carcinogenesis.

Longitudinal Assessment of Communication with Patient-Reported Outcomes During Lung Cancer Screening.

BACKGROUND: Many organizations recommend clinicians use structured communication processes, referred to as "shared decision making," to improve patient-reported outcomes for patients considering lung cancer screening (LCS). RESEARCH QUESTION: Which components of high-quality patient-centered communication are associated with decision regret and distress? STUDY DESIGN AND METHODS: We conducted a prospective, longitudinal, repeated measures, cohort study among patients undergoing lung cancer screening in three different healthcare systems. We surveyed participants using validated measures of decision regret, decision satisfaction, distress, and patient-clinician communication domains up to a year after the low-dose computed tomography (LDCT) for LCS. For longitudinal analyses, we applied a series of generalized estimating equations to measure the association of the "patient as person" communication domain, screening knowledge, and decision concordance with decision regret and distress. RESULTS: When assessed 2-4 weeks after the LDCT, 202 (58.9%) and 8 (2.3%) of 343 total respondents reported mild and moderate/severe decision regret, respectively, while 29 (9.2%) participants of 315 total reported mild distress and 19 (6.0%) moderate or greater distress. The mean ± SD decision satisfaction scores (0 to 10 scale) were 9.82 ± 0.89, 9.08 ± 1.54, and 6.13 ± 3.40 among those with no, mild, and moderate/severe regret respectively. Distress scores remained low after the LDCT, even among those with nodules. Patient-centered communication domains were not associated with decision regret or distress. INTERPRETATION: Patients undergoing LCS rarely experience moderate or greater decision regret and distress. Although many participants reported mild decision regret, most were very satisfied over the year after their LDCT for LCS. Communication processes were not associated with regret and distress, suggesting that it may be challenging for communication interventions to reduce the harms of LCS.

Describing Physical Activity Patterns of Truck Drivers Using Actigraphy.

Background: Truck driving is a highly sedentary occupation that places workers at risk for chronic health conditions, such as obesity and high blood pressure. The primary purpose of this study was to objectively describe truck drivers' typical physical activity (PA) patterns. Methods: We used ∼7-10-day baseline PA actigraphy data samples from drivers in the Safety & Health Involvement For Truckers (SHIFT) study (n = 394). Driver PA patterns (e.g., average number of ≥10 minute Freedson bouts per week, time in bouts, and common days/times for PA) were summarized with descriptive analyses. We also compared objective accelerometer data to self-reports. Results: Drivers' weekly PA averaged 14.4 minutes (SD = 37.0), and most PA occurred between 5-6 pm on Tuesdays and Wednesdays. Drivers overestimated self-reported weekly exercise by over 60 min/week compared to accelerometer data. Conclusion: Our results suggest that objective PA assessment may be warranted over self-report when possible, and timing may be key in future PA intervention work with truck drivers.

Primary Prevention of Weight Gain Among New Bus Operators: Results of the "Success & Health Impacts For Transit operators during Onboarding" (SHIFT Onboard) Pilot Study.

OBJECTIVE: This study aimed to test the feasibility and efficacy of an enhanced onboarding intervention to prevent weight gain and support the early job success of new bus operators. METHODS: Control participants ( n = 9) completed usual practice new employee training and onboarding. Intervention participants ( n = 14) completed five supplemental trainings and four online challenges during their first year. Primary outcomes were body weight, dietary behaviors, physical activity, and sleep duration/quality. Early job success was evaluated with measures of newcomer adjustment. RESULTS: The difference between intervention and control participants in body weight change at 12-month was -6.71 lb (Cohen's d = -1.35). Differences in health behavior changes were mixed, but newcomer adjustment changes favored the intervention group. CONCLUSIONS: Results support the feasibility of enhanced onboarding for bus operators to prevent worsening health while simultaneously advancing their success as new employees.

COMMunity of Practice And Safety Support for Navigating Pain (COMPASS-NP): study protocol for a randomized controlled trial with home care workers.

BACKGROUND: Chronic pain is a prevalent and costly problem that often has occupational origins. Home care workers (HCWs) are at high risk for work-related injuries, pain, and disability. Current treatments for chronic pain emphasize medications, which are an inadequate stand-alone treatment and can produce significant adverse effects. METHODS: In this translational study, we will adapt an established work-based injury prevention and health promotion program (COMmunity of Practice And Safety Support: COMPASS) to address the needs of HCWs experiencing chronic pain. COMPASS employs peer-led, scripted group meetings that include educational content, activities, goal setting, and structured social support. The translated intervention, named COMPASS for Navigating Pain (COMPASS-NP), will be delivered in an online group format. Safety protections will be strengthened through an ergonomic self-assessment and vouchers for purchasing ergonomic tools. Educational content will integrate a self-management approach to chronic pain using proven cognitive-behavioral therapy (CBT) principles. We will use a mixed-methods hybrid type 2 evaluation approach to assess effectiveness and implementation. A cluster-randomized waitlist control design will involve 14 groups of 10 HCWs (n = 140) recruited from Washington, Oregon, and Idaho. Half of the groups will be randomly selected to complete the intervention during the first 10 weeks, while the waitlist groups serve as controls. During weeks 10-20, the waitlist groups will complete the intervention while the original intervention groups complete a follow-up period without further intervention. Our primary hypothesis is that COMPASS-NP will reduce pain interference with work and life. Secondary outcomes include injury and pain prevention behaviors, pain severity, changes in medication use, risk for opioid misuse, well-being, physical activity, and sleep. Qualitative data, including phone interviews with group facilitators and organizational partners, will evaluate the implementation and guide dissemination. DISCUSSION: The results will advance the use and knowledge of secondary prevention interventions such as ergonomic tools and cognitive behavior therapy, to reduce injury, pain, and disability and to encourage appropriate uses of analgesic medications among HCWs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05492903. Registered on 08 August 2022.

Resting coronary flow drives the daily pattern in coronary flow reserve in patients with chest pain without obstructive epicardial stenosis.

Objectives: Ischemia with no obstructive coronary artery disease (INOCA) is a risk factor for major adverse cardiovascular events and is characterized by abnormal coronary microvascular tone. In patients with INOCA, adverse cardiovascular events most commonly occur in the morning compared to other times of the day and night. Materials and methods: We tested whether coronary microvascular function varies diurnally with attenuation in the morning in patients with symptomatic coronary artery disease without significant (>50%) epicardial stenosis. We evaluated data from 17 patients studied in the AM (700-1159 h) and 11 patients in the PM (1200-1800 h). Coronary microvascular function was measured using perfusion contrast imaging at rest and after infusion of intravenous regadenoson. We calculated microvascular flow reserve as the ratio of hyperemic to resting flow. Along with independent sample t-tests, we performed bootstrapping procedures to test mean differences between AM and PM groups, using the bias-corrected and accelerated method with 5,000 bootstrapped samples. Results and conclusion: The AM and PM groups were matched for demographic and existing risk factors. Coronary microvascular flow reserve was ∼33% higher in the AM compared to the PM (P = 0.025, BCa 95% CI [0.25, 1.64]; Hedge's g = 0.89, 95% CI [0.11, 1.66]) as a result of significantly lower resting flow (∼50%) in the AM compared to the PM (P = 0.03, M Diff = -56.65, BCa 95% CI [-118.59, -2.12]; Hedge's g = -0.86, 95% CI [-1.60, -0.06]). Our observations are of clinical value and can influence diagnosis and treatment in the clinic based on the time of day of measurements.

The Tech4Rest Randomized Controlled Trial: Applying the Hierarchy of Controls to Advance the Sleep, Health, and Well-being of Team Truck Drivers.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of interventions to improve sleep, reduce fatigue, and advance the well-being of team truck drivers. METHODS: In a randomized controlled trial ( k = 24 teams; N = 49 drivers; 61.3% of planned sample), intervention teams were exposed to baseline (3-4 weeks), cab enhancements (active suspension seat, therapeutic mattress; 3-4 weeks), and cab enhancements plus a behavioral sleep-health program (1-2 months). Control teams worked as usual during the same period. RESULTS: Trends in sleep-related outcomes favored the intervention. Large and statistically significant intervention effects were observed for objectively measured physical activity (a behavioral program target). The discussion of results addresses effect sizes, statistical power, intervention exposure, and work organization. CONCLUSIONS: Trends, effect sizes, and significant findings in this rare trial provide valuable guidance for future efforts to improve working conditions and outcomes for team drivers.

Spontaneous allelic variant in deafness-blindness gene Ush1g resulting in an expanded phenotype.

Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target-specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards-walking behavior in open-field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1gbw/bw null mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner-ear hair-cell function, including a complete lack of auditory brainstem responses and vestibular-evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell's kinocilial links. Consistent with other Usher type 1 models, Ush1gbw/bw mice had no substantial retinal degeneration compared with Ush1gbw /+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene.