A SEER-Medicare Based Quality Score for Patients With Metastatic Upper Tract Urothelial Carcinoma.

BACKGROUND: Population-based studies evaluating outcomes for metastatic upper tract urothelial carcinoma (mUTUC) are sparse and rarely capture both patients with de novo (synchronous) metastases and those who progress to metastatic disease (metachronous). Herein we evaluated the outcomes and costs associated with synchronous and metachronous mUTUC, utilizing a novel Methodology. Additionally, we created a guideline-based quality score to improve care in this space. PATIENTS AND METHODS: We identified all patients with mUTUC aged 66 years and older included in the SEER-Medicare linked database between 2004 and 2012. Achievement of 3 quality criteria was assessed: (1) cancer-specific survival (CSS)>12 months; (2) receipt of systemic therapy; (3) receipt of hospice/palliative care. Total healthcare and out-of-pocket costs were evaluated. Regression analyses were performed to assess characteristics associated with quality criteria and total healthcare costs. RESULTS: Of the 1223 patients identified, at least one quality criterion was met in just 40.2% and only 54 patients (4.4%) received palliative care. In multivariable analysis, patients with synchronous mUTUC (OR:0.55, 95%CI:0.41-0.72), and at least 3 comorbidities (OR:0.68, 95%CI:0.47-0.98) were less likely to achieve at least 1 quality criterion. Meeting at least 1 quality criterion was associated with increased costs ($94,677, 95%CI:87,702-101,652 versus $63,575, 95%CI:59,598-67,552). CONCLUSIONS: Less than half of patients with mUTUC met at least 1 quality criterion. Quality score achievement was associated with a modest increase in total healthcare spending. These findings not only provide guidance for future study of rare diseases using secondary data, but also highlight inadequacies in the current management of mUTUC.

National Postoperative Opioid Prescribing Rates Following Pediatric Urology Procedures Before and After the 2018 American Academy of Pediatrics Challenge to Reduce Opioid Prescribing: A Claims Database Analysis.

OBJECTIVE: To evaluate trends in opioid prescribing rates following pediatric urologic surgery. METHODS: We queried the TriNetX Research database for patients under age 18 who underwent one of seven common pediatric urology procedures. We identified the proportion of patients that received an oral opioid prescription within 5days of surgery. The primary analysis evaluated the trend in postoperative opioid prescriptions using 3-month intervals from January 2010 to December 2022. We performed an interrupted time series analysis assessing trends in opioid prescribing patterns both before and after the American Academy of Pediatrics challenge. RESULTS: Of the 81,644 pediatric urology procedures, 29,595 (36.2%) received a postoperative opioid prescription, including 29.8% of circumcisions, 25.8% of hydrocelectomies, 39.6% of hypospadias repairs, 42.7% of pyeloplasties, 42.8% of ureteral reimplants. For all procedures we observed rising rates of opioid prescribing, increasing by 0.9% per 3-month interval prior to the challenge statement release from 2010 to 2018. We observed an overall significant decrease in opioid prescribing by 2.2% per 3-month interval following the challenge statement release. Additionally, since 2018, there was a significant decrease in opioid prescribing in all of the race, ethnicity, and age cohorts. CONCLUSION: Opioid prescribing following pediatric urology procedures has sharply decreased following the 2018 American Academy of Pediatrics challenge statement which underscores the value of cross-specialty quality improvement initiatives. Nonetheless, opioid prescribing remains high with potential racial or age disparities that warrant further investigation.

Tannerella forsythia, Fusobacterium nucleatum, and Suspected Actinomyces Causing Massive Empyema: A Case Report.

This report presents the case of a polymicrobial empyema due to Fusobacterium nucleatum, Tannerella forsythia, and suspected Actinomyces spp., presenting as several weeks of progressive shortness of breath and malaise. The patient had many risk factors for a lower respiratory tract infection, including chronic alcohol abuse, a flu-like illness months prior, and a recent invasive dental procedure. An admission CT scan showed a large right pleural effusion. Blood cultures were negative, but an aspirate from the pleural effusion showed abundant gram-positive rods that did not grow aerobically. Subsequent anaerobic cultures at a reference laboratory grew Tannerella forsythia and Fusobacterium nucleatum. This report will review the diagnostic difficulties associated with anaerobic causes of empyema in general and the specific organisms implicated in this case.

Urologic practice patterns of pediatricians: a survey from a large multisite pediatric care center.

Objective: To evaluate the practice patterns of pediatricians as they relate to common urologic concerns. Materials and methods: An anonymous 15-question survey was created and distributed to all pediatricians at our institution, a large multisite care center. This study was deemed exempt by the institutional review board. Results: 55 of the 122 (45%) providers queried responded. 93% of the participants were female, and 7.3% were male. 55% recommended testicular self-examination at adolescence, while 39% did not recommend at any age. 78% stated that they were "Fairly confident" in the exam for undescended testicle (UTD). One-third referred patients with UDT to a subspecialist upon recognition at birth, 13% at 3 months of age, and 28% at 6 months of age. 10% reported obtaining a VCUG after the first febrile urinary tract infection (UTI), 26% after the second, and 36% only if there were abnormal findings on renal ultrasound. 28% of providers reported that they refer to pediatric urology after the initial febrile UTI. 19% provided antibiotics for UTI symptoms alone with negative urinalysis and urine culture. Conclusions: Despite established guidelines, practice patterns varied among pediatricians. Pediatricians typically followed the AAP's guidelines regarding VCUGs (62%), with only a few adhering to urologic recommendations (9%). Despite the consistency between AAP and AUA guidelines regarding the age at which to refer a patient for cryptorchidism, about 70% of practitioners referred patients too early or too late. Harmonized, consolidated guidelines between pediatricians and pediatric urologists would improve patient care and efficiency of the healthcare system.

Postoperative Opioid Prescribing in Adolescents and Young Adults After Urologic Procedures Is Associated With New Persistent Opioid Use Disorder: A Large Claims Database Analysis.

OBJECTIVE: To assess the risk of persistent opioid use following various urologic procedures in adolescents and young adults. MATERIALS AND METHODS: The TriNetX LLC Diamond Network was queried for patients aged 13-21years who underwent pyeloplasty, hypospadias repair, inguinal hernia repair, inguinal orchiopexy, hydrocelectomy, or circumcision. Cohorts of patients prescribed and not prescribed postoperative opioids were created and propensity-matched for age, race/ethnicity, psychiatric diagnoses, and preoperative pain diagnoses. The primary outcome was new persistent opioid use, defined as new opioid use 3-9months after index procedure without another surgery requiring anesthesia during the postoperative timeframe. RESULTS: Of 32,789 patients identified, 66.0% received a postoperative opioid prescription. After propensity score matching for each procedure, 18,416 patients were included: 197 for pyeloplasty, 469 for hypospadias repair, 1818 for inguinal hernia repair, 2664 for inguinal orchiopexy, 534 for hydrocelectomy, and 3526 for circumcision. Overall, 0.41% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 1.69% of patients who received postoperative opioids developed new persistent opioid use (P < .05). Patients prescribed postoperative opioids had statistically higher odds of developing new persistent opioid use for hypospadias repair (RR: 17.0; 95% CI: 2.27-127.2), inguinal orchiopexy (RR: 3.46; 95% CI: 1.87-6.4), inguinal hernia repair (RR: 2.18; 95% CI: 1.07-4.44), and circumcision (RR: 4.83; 95% CI: 2.60-8.98). CONCLUSION: The use of postoperative opioids after urological procedures in adolescents and young adults is associated with a significant risk of developing new persistent opioid use.

Balance beam crossing times are slower after noise exposure in rats.

Introduction: The vestibular system integrates signals related to vision, head position, gravity, motion, and body position to provide stability during motion through the environment. Disruption in any of these systems can reduce agility and lead to changes in ability to safely navigate one's environment. Causes of vestibular decline are diverse; however, excessive noise exposure can lead to otolith organ dysfunction. Specifically, 120 decibel (dB) sound pressure level (SPL) 1.5 kHz-centered 3-octave band noise (1.5 kHz 3OBN) causes peripheral vestibular dysfunction in rats, measured by vestibular short-latency evoked potential (VsEP) and reduced calretinin-immunolabeling of calyx-only afferent terminals in the striolar region of the saccule. The present study examined the functional impact of this noise exposure condition, examining changes in motor performance after noise exposure with a balance beam crossing task. Methods: Balance beam crossing time in rats was assessed for 19 weeks before and 5 weeks after noise exposure. Balance beam crossings were scored to assess proficiency in the task. When animals were proficient, they received a single exposure to 120 dB SPL 3-octave band noise. Results: During the initial training phase slower crossing times and higher scores, including multiple failures were observed. This was followed by a period of significant improvement leading to proficiency, characterized by fast and stable crossing times and consistently low scores. After noise exposure, crossing times were significantly elevated from baseline for 4-weeks. A total of 5 weeks after noise exposure, crossing times improved, and though still trending higher than baseline, they were no longer significantly different from baseline. Discussion: These findings show that the noise-induced peripheral vestibular changes we previously observed at cellular and electro-physiological levels also have an impact at a functional level. It has been previously shown that imbalance is associated with slower walking speed in older adults and aged rats. These findings in noise-exposed rats may have implications for people who experience noisy environments and for seniors with a history of noise exposure who also experience balance disorders and may be at increased fall risk.

Influence of Supervised Maternal Aerobic Exercise during Pregnancy on 1-Month-Old Neonatal Cardiac Function and Outflow: A Pilot Study.

PURPOSE: The objective of this study is to assess the effects of supervised, recommended levels of prenatal aerobic exercise on 1-month-old infant cardiac function. METHODS: Eligible pregnant women were randomly assigned to either an aerobic exercise group that participated in 150 min of supervised, moderate-intensity (40% to 59% V̇O 2peak , 12 to 14 on Borg rating of perceived exertion) aerobic exercise per week for 24 wk or more or a nonexercising group that consisted of 150 min·wk -1 of relaxation techniques. One-month-old infant echocardiogram was performed to assess infant cardiac function , including heart rate (HR), left-ventricular stroke volume, cardiac output, cardiac index, ejection fraction, fractional shortening, and velocity time integral at the aortic valve. Pearson correlation analyses and linear regression models were performed. RESULTS: Prenatal aerobic exercise was negatively correlated with infant resting HR ( r = -0.311, P = 0.02). Similarly, when controlling for infant sex and activity state, exercise level/volume ( ß = -0.316; 95% CI, -0.029 to -0.002; P = 0.02) predicted resting infant HR ( R2 = 0.18, P = 0.02). In infants of overweight/obese women, infants of aerobic exercisers had increased fractional shortening ( P = 0.03). In addition, infant ventricular ejection fraction was correlated with maternal exercise attendance ( r = 0.418, P = 0.03) as well as a trend for exercise level ( r = 0.351, P = 0.08). Similarly, the only significant regression model for infants of overweight/obese women controls infant activity state ( ß = -0.444; 95% CI, -0.05 to -0.01; P = 0.006) and maternal exercise level ( ß = 0.492; 95% CI, 5.46-28.74; P = 0.01) predicting infant resting HR ( F = 5.79, R2 = 0.40, P = 0.003). CONCLUSIONS: The findings of this study demonstrate that women participating in exercise in the second and third trimesters of their pregnancy may have infants with increased cardiac function at 1 month of age. Importantly, the cardiac function effects were further augmented for infants born to overweight/obese women.

Health4Life eHealth intervention to modify multiple lifestyle risk behaviours among adolescent students in Australia: a cluster-randomised controlled trial.

BACKGROUND: Lifestyle risk behaviours are prevalent among adolescents and commonly co-occur, but current intervention approaches tend to focus on single risk behaviours. This study aimed to evaluate the efficacy of the eHealth intervention Health4Life in modifying six key lifestyle risk behaviours (ie, alcohol use, tobacco smoking, recreational screen time, physical inactivity, poor diet, and poor sleep, known as the Big 6) among adolescents. METHODS: We conducted a cluster-randomised controlled trial in secondary schools that had a minimum of 30 year 7 students, in three Australian states. A biostatistician randomly allocated schools (1:1) to Health4Life (a six-module, web-based programme and accompanying smartphone app) or an active control group (usual health education) with the Blockrand function in R, stratified by site and school gender composition. All students aged 11-13 years who were fluent in English and attended participating schools were eligible. Teachers, students, and researchers were not masked to allocation. Primary outcomes were alcohol use, tobacco use, recreational screen time, moderate to vigorous physical activity (MVPA), sugar-sweetened beverage intake, and sleep duration at 24 months, measured by self-report surveys, and analysed in all students who were eligible at baseline. Latent growth models estimated between-group change over time. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000431123). FINDINGS: Between April 1, 2019, and Sept 27, 2019, we recruited 85 schools (9280 students), of which 71 schools with 6640 eligible students (36 schools [3610 students] assigned to the intervention and 35 [3030 students] to the control) completed the baseline survey. 14 schools were excluded from the final analysis or withdrew, mostly due to a lack of time. We found no between-group differences for alcohol use (odds ratio 1·24, 95% CI 0·58-2·64), smoking (1·68, 0·76-3·72), screen time (0·79, 0·59-1·06), MVPA (0·82, 0·62-1·09), sugar-sweetened beverage intake (1·02, 0·82-1·26), or sleep (0·91, 0·72-1·14) at 24 months. No adverse events were reported during this trial. INTERPRETATION: Health4Life was not effective in modifying risk behaviours. Our results provide new knowledge about eHealth multiple health behaviour change interventions. However, further research is needed to improve efficacy. FUNDING: Paul Ramsay Foundation, the Australian National Health and Medical Research Council, the Australian Government Department of Health and Aged Care, and the US National Institutes of Health.

Sex Differences in the Long-Term Consequences of Stroke.

Stroke is the fifth leading cause of death and as healthcare intervention improves, the number of stroke survivors has also increased. Furthermore, there exists a subgroup of younger adults, who suffer stroke and survive. Given the overall improved survival rate, bettering our understanding of long-term stroke outcomes is critical. In this review we will explore the causes and challenges of known long-term consequences of stroke and if present, their corresponding sex differences in both old and young survivors. We have separated these long-term post-stroke consequences into three categories: mobility and muscle weakness, memory and cognitive deficits, and mental health and mood. Lastly, we discuss the potential of common preclinical stroke models to contribute to our understanding of long-term outcomes following stroke.

Measurement Properties of Smartphone Approaches to Assess Physical Activity in Healthy Young People: Systematic Review.

BACKGROUND: Physical inactivity is a preventable risk factor for several chronic diseases and one of the driving forces behind the growing global burden of disease. Recent evidence has shown that interventions using mobile smartphone apps can promote a significant increase in physical activity (PA) levels. However, the accuracy and reliability of using apps is unknown. OBJECTIVE: The aim of our review was to determine the accuracy and reliability of using mobile apps to measure PA levels in young people. We conducted a systematic review guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). METHODS: Studies published from 2007 to 2020 were sourced from 8 databases-Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsychINFO (EBSCOhost), CINAHL (EBSCOhost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library database. Studies were conducted in young people aged 10-24 years and without chronic illnesses, who evaluated a mobile app's ability to measure PA. Primary outcomes included validity, reliability, and responsiveness of the measurement approach. Duplicate screening was conducted for eligibility, data extraction, and assessing the risk of bias. Results were reported as a systematic review. The main physical activity measures evaluated for each study were the following: total PA time (min/day or min/week), total moderate to vigorous PA per week, daily step count, intensity measure (heart rate), and frequency measure (days per week). RESULTS: Of the 149 identified studies, 5 met the inclusion criteria (322 participants, 176 female; mean age 14, SD 3 years). A total of 3 studies measured criterion validity and compared PA measured via apps against PA measured via an Actigraph accelerometer. The 2 studies that reported on construct validity identified a significant difference between self-reported PA and the objective measure. Only 1 of the 5 apps examined was available to the public, and although this app was highly accepted by young people, the app recorded PA to be significantly different to participants' self-reported PA. CONCLUSIONS: Overall, few studies assess the reliability, validity, and responsiveness of mobile apps to measure PA in healthy young people, with studies typically only reporting on one measurement property. Of the 3 studies that measured validity, all concluded that mobile phones were acceptable and valid tools. More research is needed into the validity and reliability of smartphone apps to measure PA levels in this population as well as in populations with other characteristics, including other age groups and those with chronic diseases. TRIAL REGISTRATION: PROSPERO CRD42019122242; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=122242.

Noise overstimulation of young adult UMHET4 mice accelerates age-related hearing loss.

Many factors contribute to hearing loss commonly found in older adults. There can be natural aging of cellular elements, hearing loss previously induced by environmental factors such as noise or ototoxic drugs as well as genetic and epigenetic influences. Even when noise overstimulation does not immediately cause permanent hearing loss it has recently been shown to increase later age-related hearing loss (ARHL). The present study further investigated this condition in the UMHET4 mouse model by comparing a small arms fire (SAF)-like impulse noise exposure that has the greatest immediate effect in more apical cochlear regions to a broadband noise (BBN) exposure that has the greatest immediate effect in more basal cochlear regions. Both noise exposures were given at levels that only induced temporary auditory brainstem response (ABR) threshold shifts (TS). Mice were noise exposed at 5 months of age followed by ABR assessment at 6, 12, 18, 21, and 24 months of age. Mice that received the SAF-like impulse noise had accelerated age-related TS at 4 kHz that appeared at 12 months of age (significantly increased compared to no-noise controls). This increased TS at 4 kHz continued at 18 and 21 months but was no longer significantly greater at 24 months of age. The SAF-like impulse noise also induced a significantly greater mean TS at 48 kHz, first appearing at 18 months of age and continuing to be significantly greater than controls at 21 and 24 months. The BBN induced a different pace and pattern of enhanced age-related ABR TS. The mean TS for the BBN group first became significantly greater than controls at 18 months of age and only at 48 kHz. It remained significantly greater than controls at 21 months but was no longer significantly greater at 24 months of age. Results, therefore, show different influences on ARHL for the two different noise exposure conditions. Noise-induced enhancement appears to provide more an acceleration than overall total increase in ARHL.

Measurement Properties of Smartphone Approaches to Assess Diet, Alcohol Use, and Tobacco Use: Systematic Review.

BACKGROUND: Poor diet, alcohol use, and tobacco smoking have been identified as strong determinants of chronic diseases, such as cardiovascular disease, diabetes, and cancer. Smartphones have the potential to provide a real-time, pervasive, unobtrusive, and cost-effective way to measure these health behaviors and deliver instant feedback to users. Despite this, the validity of using smartphones to measure these behaviors is largely unknown. OBJECTIVE: The aim of our review is to identify existing smartphone-based approaches to measure these health behaviors and critically appraise the quality of their measurement properties. METHODS: We conducted a systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsycINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library databases in March 2020. Articles that were written in English; reported measuring diet, alcohol use, or tobacco use via a smartphone; and reported on at least one measurement property (eg, validity, reliability, and responsiveness) were eligible. The methodological quality of the included studies was assessed using the Consensus-Based Standards for the Selection of Health Measurement Instruments Risk of Bias checklist. Outcomes were summarized in a narrative synthesis. This systematic review was registered with PROSPERO, identifier CRD42019122242. RESULTS: Of 12,261 records, 72 studies describing the measurement properties of smartphone-based approaches to measure diet (48/72, 67%), alcohol use (16/72, 22%), and tobacco use (8/72, 11%) were identified and included in this review. Across the health behaviors, 18 different measurement techniques were used in smartphones. The measurement properties most commonly examined were construct validity, measurement error, and criterion validity. The results varied by behavior and measurement approach, and the methodological quality of the studies varied widely. Most studies investigating the measurement of diet and alcohol received very good or adequate methodological quality ratings, that is, 73% (35/48) and 69% (11/16), respectively, whereas only 13% (1/8) investigating the measurement of tobacco use received a very good or adequate rating. CONCLUSIONS: This review is the first to provide evidence regarding the different types of smartphone-based approaches currently used to measure key behavioral risk factors for chronic diseases (diet, alcohol use, and tobacco use) and the quality of their measurement properties. A total of 19 measurement techniques were identified, most of which assessed dietary behaviors (48/72, 67%). Some evidence exists to support the reliability and validity of using smartphones to assess these behaviors; however, the results varied by behavior and measurement approach. The methodological quality of the included studies also varied. Overall, more high-quality studies validating smartphone-based approaches against criterion measures are needed. Further research investigating the use of smartphones to assess alcohol and tobacco use and objective measurement approaches is also needed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-https://doi.org/10.1186/s13643-020-01375-w.

Long term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer.

BACKGROUND: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models. RESULTS: A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781). CONCLUSIONS AND RELEVANCE: The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.

Transient peripheral vestibular hypofunction measured with vestibular short-latency evoked potentials following noise exposure in rats.

Exposure to 120 dB sound pressure level (SPL) band-limited noise results in delayed onset latency and reduced vestibular short-latency evoked potential (VsEP) responses. These changes are still present 4 wk after noise overstimulation. Noise-induced hearing loss (NIHL) has been shown to vary in extent and duration based on the noise intensity. This study investigated whether noise-induced peripheral vestibular hypofunction (NPVH) would also decrease in extent and/or duration with less intense noise exposure. In the present study, rats were exposed to a less intense noise (110 dB SPL) but for the same duration (6 h) and frequency range (500-4,000 Hz) as used in previous studies. The VsEP was assessed 1, 3, 7, 14, 21, and 28 days after noise exposure. In contrast to 120 dB SPL noise exposure, the 110 dB SPL noise exposures produced smaller deficits in VsEP responses that fully recovered in 62% (13/21) of animals within 1 wk. These findings suggest that NPVH, a loss or attenuation of VsEP responses with a requirement for elevated stimulus intensity to elicit measurable responses, is similar to NIHL, that is, lower sound levels produce a smaller or transient deficit. These results show that it will be important to determine the extent and duration of vestibular hypofunction for different noise exposure conditions and their impact on balance.NEW & NOTEWORTHY This is the first study to show a temporary noise-induced peripheral vestibular hypofunction that recovers following exposure to continuous noise.

Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice.

Our previous study demonstrated rapamycin added to diet at 4 months of age had significantly less age-related outer hair cell loss in the basal half of the cochlea at 22 months of age compared to mice without rapamycin. The present study tested adding rapamycin to diet later in life, at 14 months of age, and added a longitudinal assessment of auditory brain stem response (ABR). The present study used UMHET4 mice, a 4 way cross in which all grandparental strains lack the Cdh23753A allele that predisposes to early onset, progressive hearing loss. UMHET4 mice typically have normal hearing until 16-17 months, then exhibit threshold shifts at low frequencies/apical cochlea and later in more basal high frequency regions. ABR thresholds at 4, 12, 24, and 48 kHz were assessed at 12, 18, and 24 months of age and compared to baseline ABR thresholds acquired at 5 months of age to determine threshold shifts (TS). There was no TS at 12 months of age at any frequency tested. At 18 months of age mice with rapamycin added to diet at 14 months had a significantly lower mean TS at 4 and 12 kHz compared to mice on control diet with no significant difference at 24 and 48 kHz. At 24 months of age, the mean 4 kHz TS in rapamycin diet group was no longer significantly lower than the control diet group, while the 12 kHz mean remained significantly lower. Mean TS at 24 and 48 kHz in the rapamycin diet group became significantly lower than in the control diet group at 24 months. Hair cell counts at 24 months showed large loss in the apical half of most rapamycin and control diet mice cochleae with no significant difference between groups. There was only mild outer hair cell loss in the basal half of rapamycin and control diet mice cochleae with no significant difference between groups. The results show that a later life addition of rapamycin can decrease age-related hearing loss in the mouse model, however, it also suggests that this decrease is a delay/deceleration rather than a complete prevention.

Effects of Noise Exposure on the Vestibular System: A Systematic Review.

Despite our understanding of the impact of noise-induced damage to the auditory system, much less is known about the impact of noise exposure on the vestibular system. In this article, we review the anatomical, physiological, and functional evidence for noise-induced damage to peripheral and central vestibular structures. Morphological studies in several animal models have demonstrated cellular damage throughout the peripheral vestibular system and particularly in the otolith organs; however, there is a paucity of data on the effect of noise exposure on human vestibular end organs. Physiological studies have corroborated morphological studies by demonstrating disruption across vestibular pathways with otolith-mediated pathways impacted more than semicircular canal-mediated pathways. Similar to the temporary threshold shifts observed in the auditory system, physiological studies in animals have suggested a capacity for recovery following noise-induced vestibular damage. Human studies have demonstrated that diminished sacculo-collic responses are related to the severity of noise-induced hearing loss, and dose-dependent vestibular deficits following noise exposure have been corroborated in animal models. Further work is needed to better understand the physiological and functional consequences of noise-induced vestibular impairment in animals and humans.

A Synthetic Approach to ß-Functionalized Naphtho[2,3]porphyrins.

A concise synthetic method has been developed to access functionalized naphtho[2,3]porphyrins through combining two sequence reactions involving a Heck-electrocyclization-aromatization sequence and a Wittig-Knovenegal sequence. Using this method, mononaphtho[2,3]porphyrin (NP-1), opp-dinaphtho[2,3]porphyrin (NP-2), and push-pull naphtho[2,3]porphyrin (NP-3) have been prepared. These naphtho[2,3]porphyrins displayed interesting optical and electrochemical properties. Excellent efficiencies of singlet oxygen generation were obtained for these naphtho[2,3]porphyrins.

Gonadal hormones and stroke risk: PCOS as a case study.

It is well known that stroke incidence and outcome is sex-dependent and influenced by age and gonadal hormones. In post-menopausal and/or aged females, declining estrogen levels increases stroke risk. However, women who experience early menopause also have an increase in stroke risk. This suggests that, regardless of age, gonadal hormones regulate stroke risk and severity. This review discusses prolonged gonadal hormone dysfunction in a common female endocrine disorder known as polycystic ovarian syndrome, PCOS, and the associated increased risk of stroke due to resulting hyperandrogenism and metabolic comorbidities.