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Abstract Tinnitus, reduced sound-level tolerance, and difficulties hearing in noisy environments are the most common complaints associated with sensorineural hearing loss in adult populations. This study aims to clarify if cochlear neural degeneration estimated in a large pool of participants with normal audiograms is associated with self-report of tinnitus using a test battery probing the different stages of the auditory processing from hair cell responses to the auditory reflexes of the brainstem. Self-report of chronic tinnitus was significantly associated with (1) reduced cochlear nerve responses, (2) weaker middle-ear muscle reflexes, (3) stronger medial olivocochlear efferent reflexes and (4) hyperactivity in the central auditory pathways. These results support the model of tinnitus generation whereby decreased neural activity from a damaged cochlea can elicit hyperactivity from decreased inhibition in the central nervous system.

Abstract Studies have suggested that cancerous tissue has a lower 15N/14N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the 15N/14N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, 15N/14N was negatively correlated with tumor cell density. The magnitude of 15N depletion for a given tumor cell density was consistent across different types of lung cancer, ductal in situ and invasive breast carcinoma, and urothelial carcinoma, suggesting similar elevations in the anabolism-to-catabolism ratio. However, tumor 15N depletion was higher in a more aggressive metaplastic breast carcinoma. These findings may indicate the ability of certain cancers to more effectively channel N towards growth. Our results support 15N/14N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells.

Abstract The current gold standard of clinical hearing assessment includes a pure-tone audiogram combined with a word recognition task. This retrospective study tests the hypothesis that deficits in word recognition that cannot be explained by loss in audibility or cognition may reflect underlying cochlear nerve degeneration (CND). We collected the audiological data of nearly 96,000 ears from patients with normal hearing, conductive hearing loss (CHL) and a variety of sensorineural etiologies including (1) age-related hearing loss (ARHL); (2) neuropathy related to vestibular schwannoma or neurofibromatosis of type 2; (3) Ménière’s disease; (4) sudden sensorineural hearing loss (SSNHL), (5) exposure to ototoxic drugs (carboplatin and/or cisplatin, vancomycin or gentamicin) or (6) noise damage including those with a 4-kHz “noise notch” or reporting occupational or recreational noise exposure. Word recognition was scored using CID W-22 monosyllabic word lists. The Articulation Index was used to predict the speech intelligibility curve using a transfer function for CID W-22. The level at which maximal intelligibility was predicted was used as presentation level (70 dB HL minimum). Word scores decreased dramatically with age and thresholds in all groups with SNHL etiologies, but relatively little in the conductive hearing loss group. Discrepancies between measured and predicted word scores were largest in patients with neuropathy, Ménière’s disease and SSNHL, intermediate in the noise-damage and ototoxic drug groups, and smallest in the ARHL group. In the CHL group, the measured and predicted word scores were very similar. Since word-score predictions assume that audiometric losses can be compensated by increasing stimulus level, their accuracy in predicting word score for CHL patients is unsurprising. The lack of a strong age effect on word scores in CHL shows that cognitive decline is not a major factor in this test. Amongst the possible contributions to word score discrepancies, CND is a prime candidate: it should worsen intelligibility without affecting thresholds and has been documented in human temporal bones with SNHL. Comparing the audiological trends observed here with the existing histopathological literature supports the notion that word score discrepancies may be a useful CND metric.

Abstract The lactic acid bacteria (LAB) Lactobacillus plantarum (strains 22F and 25F) and Pediococcus acidilactici (strain 72N) have appeared promising as replacements for antibiotics in in vitro studies. Microencapsulation, especially by the spray-drying method, has been used to preserve their numbers and characteristics during storage and digestion. This study compared the efficacy of these strains and their microencapsulated form with antibiotic usage on growth performance, faecal microbial counts, and intestinal morphology in nursing-finishing pigs. A total of 240 healthy neonatal pigs were treated on days 0, 3, 6, 9, and 12 after cross-fostering. Sterile peptone water was delivered orally to the control and antibiotic groups. Spray-dried Lactobacillus plantarum strain 22F stored for 6-months was administered to piglets in the spraydry group. Three ml of each the three fresh strains (109 CFU/mL) were orally administered to piglets in each group. All pigs received the basal diets, but these were supplemented with routine antibiotic for the antibiotic group. Pigs in all the probiotic supplemented groups exhibited a better average daily gain and feed conversion ratio than those of the controls in the nursery and grower phases. Probiotic supplementation increased viable lactobacilli and decreased enterobacterial counts. Antibiotic additives reduced both enterobacterial and lactobacilli counts. Villous height and villous height:crypt depth ratio were greater in probiotic and antibiotic supplemented pigs comparing to the controls, especially in the jejunum. The results demonstrated the feasibility of using these strains as a substitute for antibiotics and the practicality of the microencapsulation protocol for use in swine farms.

Abstract Mutations in the TGFβR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFβR2 mutation, initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFβR2 mutations. ECG findings from 58 mutation carriers patients (TGFβR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFβR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p