The acoustically evoked short latency negative response (ASNR) in a unilaterally deaf cat with histologically-confirmed cochleosaccular degeneration

BACKGROUND: A negative potential is occasionally recorded in humans and animals with profound deafness during brainstem auditory evoked potential (BAER) tests if loud intensities are used. This acoustically evoked short latency negative response (ASNR) is hypothesized to be of saccular origin. The sensitivity to sound of vestibular end organs is also used to produce vestibular evoked myogenic potentials (VEMP), a test that evaluates vestibular function. The same saccular origin is accepted also for VEMP. CASE PRESENTATION: A neutered male white domestic short hair cat presented with profound deafness and an ASNR in the left ear during BAER test performed when he was 8 months old. BAER tracings were substantially unchanged at the age of 12 years, immediately before euthanasia that was requested by the owner for the presence of an unrelated neoplastic disorder. The cat underwent a complete post-mortem necropsy including histopathology of the middle and inner ears. Histopathologic results confirmed the presence of a cochleosaccular degeneration of the left ear while the cochlea and sacculus of the right ear and the utriculus and semicircular canals of both ears were histologically normal. CONCLUSIONS: This case report describes the auditory and histopathologic findings of a cat that showed an ASNR during BAER test despite the presence of cochleosaccular deafness. These results confirm that a saccular origin for the ASNR in this case, and in general in cats and dogs with congenital deafness associated with white pigmentation, is improbable. The hypothesis that the sacculus is the vestibular end organ responsible for the generation of the ASNR and VEMP in humans comes mainly from animal studies. The findings in this report may change the clinical interpretation of the results of BAER and VEMP not only in companion animals, but in humans as well

Circadian Activity of Topical 0.05% Betamethasone Dipropionate in Human Skin In Vivo

The influence of treatment duration, vehicle, and time of day of application on topical 0.05% betamethasone dipropionate uptake into human stratum corneum and the resulting skin- blanching response was investigated in human subjects. Drug uptake into stratum corneum and the resulting skin color changes measured with a chromameter demonstrate an equilibrium delay. Maximal drug uptake occurred at 2 h, whereas maximal skin color changes occurred 6h after a single application. Extent of decreased skin color was dependent on vehicle, treatment duration, and time of day of application. Time of maximal decreased skin color occurred at midnight independent of vehicle, treatment duration, or time of day of application. This time of maximal drug activity coincides with the well-known time period of lowest circulating cortisol concentrations (2000-0400 h). Application of a single 2- or 6-h dose of the 0.05% cream at 1600h produced more extensive and prolonged changes in skin color over 24h than a 0900-h application in the same subject. These data demonstrate that the extent and duration of topical corticosteroid activity in human skin is influenced by vehicle, treatment duration, and time of day of application. The prolonged changes in skin color measured with a single dose applied at 1600h suggest that a once-a-day dosing regimen in the late afternoon may be sufficient for dermatologic therapy. Elucidation of these circadian responses with topical corticosteroids may provide a rational basis for the future re-evaluation of the appropriate therapeutic regimen with this class of drugs in dermatologic medicine

An innovative quality improvement curriculum for third-year medical students

Background: Competence in quality improvement (QI) is a priority for medical students. We describe a self-directed QI skills curriculum for medical students in a 1-year longitudinal integrated third-year clerkship: an ideal context to learn and practice QI. Methods: Two groups of four students identified a quality gap, described existing efforts to address the gap, made quantifying measures, and proposed a QI intervention. The program was assessed with knowledge and attitude surveys and a validated tool for rating trainee QI proposals. Reaction to the curriculum was assessed by survey and focus group. Results: Knowledge of QI concepts did not improve (mean knowledge score±SD): pre: 5.9±1.5 vs. post: 6.6±1.3, p=0.20. There were significant improvements in attitudes (mean topic attitude score±SD) toward the value of QI (pre: 9.9±1.8 vs. post: 12.6±1.9, p=0.03) and confidence in QI skills (pre: 13.4±2.8 vs. post: 16.1±3.0, p=0.05). Proposals lacked sufficient analysis of interventions and evaluation plans. Reaction was mixed, including appreciation for the experience and frustration with finding appropriate mentorship. Conclusion: Clinical-year students were able to conduct a self-directed QI project. Lack of improvement in QI knowledge suggests that self-directed learning in this domain may be insufficient without targeted didactics. Higher order skills such as developing measurement plans would benefit from explicit instruction and mentorship. Lessons from this experience will allow educators to better target QI curricula to medical students in the clinical years

Disruption of information processing in schizophrenia: The time perspective

AbstractWe review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted

The Pulsation of Chi Cygni Imaged by Optical Interferometry; a Novel Technique to Derive Distance and Mass of Mira Stars

We present infrared interferometric imaging of the S-type Mira star Chi Cygni. The object was observed at four different epochs in 2005-2006 with the IOTA optical interferometer (H band). Images show up to 40% variation in the stellar diameter, as well as significant changes in the limb darkening and stellar inhomogeneities. Model fitting gave precise time-dependent values of the stellar diameter, and reveals presence and displacement of a warm molecular layer. The star radius, corrected for limb darkening, has a mean value of 12.1 mas and shows a 5.1mas amplitude pulsation. Minimum diameter was observed at phase 0.94+/-0.01. Maximum temperature was observed several days later at phase 1.02+/-0.02. We also show that combining the angular acceleration of the molecular layer with CO (Delta v = 3) radial velocity measurements yields a 5.9+/-1.5 mas parallax. The constant acceleration of the CO molecules -- during 80% of the pulsation cycle -- lead us to argument for a free-falling layer. The acceleration is compatible with a gravitational field produced by a 2.1(+1.5/-0.7) solar mass star. This last value is in agreement with fundamental mode pulsator models. We foresee increased development of techniques consisting in combining radial velocity with interferometric angular measurements, ultimately allowing total mapping of the speed, density, and position of the diverse species in pulsation driven atmospheres.Comment: 36 pages, accepted in Ap

Influence of total sugar intake on metabolic blood markers at 8 years of age in the Childhood Obesity Project

PURPOSE We aimed to characterize the association of dietary sugar intake with blood lipids and glucose-related markers in childhood. METHODS Data from the multicentric European Childhood Obesity Project Trial were used. Three-day weighed dietary records were obtained at 8~years of age along with serum concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), glucose, and insulin. Total sugar intake comprised all mono- and disaccharides; different sugar sources were defined. Linear regression models were applied to investigate the cross-sectional association of total sugar intake with blood lipids and glucose-related markers with adjustment for total energy intake using the residual method. RESULTS Data were available for 325 children. Children consumed on average 332~kcal (SD 110) and 21% (SD 6) of energy from total sugar. In an energy-adjusted model, an increase of 100~kcal from total sugar per day was significantly associated with a z score HDL-C decrease (-~0.14; 95% CI -~0.01, -~0.27; p value = 0.031). Concerning different food groups of total sugar intake, 100~kcal total sugar from sweetened beverages was negatively associated with z score HDL-C (-~1.67; 95% CI -~0.42, -~2.91; p value = 0.009), while total sugar from milk products was positively related to z score HDL-C (1.38, 95% CI 0.03, 2.72; p value = 0.045). None of the other blood lipids or glucose-related markers showed a significant relationship with total sugar intake. CONCLUSION Increasing dietary total sugar intake in children, especially from sweetened beverages, was associated with unfavorable effects on HDL-C, which might increase the long-term risk for dyslipidemia and cardiovascular disease. CLINICAL TRIAL REGISTRY ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: https://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1

Marker-Assisted Pyramiding of Blast-Resistance Genes in a japonica Elite Rice Cultivar through Forward and Background Selection

Rice blast, caused by Pyricularia oryzae, is one of the main rice diseases worldwide. The pyramiding of blast-resistance (Pi) genes, coupled to Marker-Assisted BackCrossing (MABC), provides broad-spectrum and potentially durable resistance while limiting the donor genome in the background of an elite cultivar. In this work, MABC coupled to foreground and background selections based on KASP marker assays has been applied to introgress four Pi genes (Piz, Pib, Pita, and Pik) in a renowned japonica Italian rice variety, highly susceptible to blast. Molecular analyses on the backcross (BC) lines highlighted the presence of an additional blast-resistance gene, the Pita-linked Pita2/Ptr gene, therefore increasing the number of blast-resistance introgressed genes to five. The recurrent genome was recovered up to 95.65%. Several lines carrying four (including Pita2) Pi genes with high recovery percentage levels were also obtained. Phenotypic evaluations confirmed the effectiveness of the pyramided lines against multivirulent strains, which also had broad patterns of resistance in comparison to those expected based on the pyramided Pi genes. The developed blast-resistant japonica lines represent useful donors of multiple blast-resistance genes for future rice-breeding programs related to the japonica group

Milliarcsecond angular resolution of reddened stellar sources in the vicinity of the Galactic Center

For the first time, the lunar occultation technique has been employed on a very large telescope in the near-IR with the aim of achieving systematically milliarcsecond resolution on stellar sources. We have demonstrated the burst mode of the ISAAC instrument, using a fast read-out on a small area of the detector to record many tens of seconds of data at a time on fields of few squared arcsec. We have used the opportunity to record a large number of LO events during a passage of the Moon close to the Galactic Center in March 2006. We have developed a data pipeline for the treatment of LO data, including the automated estimation of the main data analysis parameters using a wavelet-based method, and the preliminary fitting and plotting of all light curves. We recorded 51 LO events over about four hours. Of these, 30 resulted of sufficient quality to enable a detailed fitting. We detected two binaries with subarcsec projected separation and three stars with a marginally resolved angular diameter of about 2 mas. Two more SiO masers, were found to be resolved and in one case we could recover the brightness profile of the extended emission, which is well consistent with an optically thin shell. The remaining unresolved stars were used to characterize the performance of the method. The LO technique at a very large telescope is a powerful and efficient method to achieve angular resolution, sensitivity, and dynamic range that are among the best possible today with any technique. The selection of targets is naturally limited and LOs are fixed-time events, however each observation requires only a few minutes including overheads. As such, LOs are ideally suited to fill small gaps of idle time between standard observations.Comment: A&A in pres

Tetramolecular G-quadruplex formation pathways studied by electrospray mass spectrometry

Electrospray mass spectrometry was used to investigate the mechanism of tetramolecular G-quadruplex formation by the DNA oligonucleotide dTG5T, in ammonium acetate. The intermediates and products were separated according to their mass (number of strands and inner cations) and quantified. The study of the temporal evolution of each species allows us to propose the following formation mechanism. (i) Monomers, dimers and trimers are present at equilibrium already in the absence of ammonium acetate. (ii) The addition of cations promotes the formation of tetramers and pentamers that incorporate ammonium ions and therefore presumably have stacked guanine quartets in their structure. (iii) The pentamers eventually disappear and tetramers become predominant. However, these tetramers do not have their four strands perfectly aligned to give five G-quartets: the structures contain one ammonium ion too few, and ion mobility spectrometry shows that their conformation is more extended. (iv) At 4°C, the rearrangement of the kinetically trapped tetramers with presumably slipped strand(s) into the perfect G-quadruplex structure is extremely slow (not complete after 4 months). We also show that the addition of methanol to the monomer solution significantly accelerates the cation-induced G-quadruplex assembly