Tinnitus in Normal-Hearing Participants after Exposure to Intense Low-Frequency Sound and in Meniere's Disease Patients

Tinnitus is one of the three classical symptoms of Meniere's disease (MD), an inner ear disease that is often accompanied by endolymphatic hydrops. Previous studies indicate that tinnitus in MD patients is dominated by low frequencies, whereas tinnitus in non-hydropic pathologies is typically higher in frequency. Tinnitus of rather low-frequency (LF) quality was also reported to occur for about 90 s in normal-hearing participants after presentation of intense, LF sound (120 dB SPL, 30 Hz, 90 s). LF sound has been demonstrated to also cause temporary endolymphatic hydrops in animal models. Here, we quantify tinnitus in two study groups with chronic (MD patients) and presumably transient endolymphatic hydrops (normal-hearing participants after LF exposure) with a psychophysical procedure. Participants matched their tinnitus either with a pure tone of adjustable frequency and level or with a noise of adjustable spectral shape and level. Sensation levels of matching stimuli were lower for MD patients (mean: 8 dB SL) than for normal-hearing participants (mean: 15 dB SL). Transient tinnitus after LF-exposure occurred in all normal-hearing participants (N = 28). About half of the normal-hearing participants matched noise to their tinnitus, the other half chose a pure tone with frequencies below 2 kHz. MD patients matched their tinnitus with either high-frequency pure tones, mainly above 3 kHz, or with a noise. Despite a significant proportion of MD patients matching low-pass (roaring) noises to their tinnitus, the range of matched stimuli was more heterogeneous than previous data suggested. We propose that in those participants with noise-like tinnitus, the percept is probably generated by increased spontaneous activity of auditory nerve fibers with a broad range of characteristic frequencies, due to an impaired ion balance in the cochlea. For tonal tinnitus, additional mechanisms are conceivable: focal hair cell loss can result in decreased auditory nerve firing and a central auditory overcompensation. Also, normal-hearing participants after LF-exposure experience alterations in spontaneous otoacoustic emissions, which may contribute to a transient tonal tinnitus

Propiedades psicométricas del Hopkins Symptom Checklist (HSCL-11) en Argentina: Un instrumento para monitoreo y feedback en psicoterapia

We failed to find brief instruments validated in Argentina to explore and monitor psychological symptoms from psychotherapy patients. This paper presents the Argentinian adaptation of the Hopkins Symptoms Checklist (HSCL-11) and analyzes its psychometric properties. A sample of 356 participants completed the HSCL-11 adaptation, along with other measures of depression, anxiety, and well-being. We analyzed Cronbach’s alpha and item-total correlations adjusted. We ran confirmatory factor analysis, correlations among the measures, and  examined differences in HSCL-11 between subjects who were psychotherapy patients and those who were not. We found evidence of adequate internal consistency and item homogeneity, as well as construct validity, concurrent validity, and criterion validity. Results showed evidence of reliability and validity for the HSCL-11 Argentinian adaptation, suggesting that it might represent a meaningful resource for the evaluation and treatment of mental disorders in Argentina.No se han encontrado instrumentos breves válidos en Argentina para monitorear sintomatología psicológica en psicoterapia. Este trabajo presenta la adaptación argentina del Hopkins Symptoms Checklist (HSCL-11) y estudia sus propiedades psicométricas. Una muestra de 356 participantes completó la adaptación del HSCL-11 junto con medidas de depresión, ansiedad y bienestar. Se computaron el coeficiente alfa de Cronbach y correlaciones ítem-total corregidas. Se realizó un análisis factorial confirmatorio, se estudiaron sus correlaciones con las otras medidas y se analizaron las diferencias en HSCL-11 entre pacientes y no pacientes de terapia. Se observaron evidencias de adecuada consistencia interna y homogeneidad de ítems, así como también de validez de constructo, validez concurrente y validez de criterio. Los resultados mostraron evidencias deconfiabilidad y validez de la versión argentina del HSCL-11, sugiriendo que podría representar un instrumento valioso para la evaluación y el tratamiento de patologías mentales en el país

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)

Streptococcus pneumoniae Serotype 1 Capsular Polysaccharide Induces CD8+CD28− Regulatory T Lymphocytes by TCR Crosslinking

Zwitterionic capsular polysaccharides (ZPS) of commensal bacteria are characterized by having both positive and negative charged substituents on each repeating unit of a highly repetitive structure that has an α-helix configuration. In this paper we look at the immune response of CD8+ T cells to ZPSs. Intraperitoneal application of the ZPS Sp1 from Streptococcus pneumoniae serotype 1 induces CD8+CD28− T cells in the spleen and peritoneal cavity of WT mice. However, chemically modified Sp1 (mSp1) without the positive charge and resembling common negatively charged polysaccharides fails to induce CD8+CD28− T lymphocytes. The Sp1-induced CD8+CD28− T lymphocytes are CD122lowCTLA-4+CD39+. They synthesize IL-10 and TGF-β. The Sp1-induced CD8+CD28− T cells exhibit immunosuppressive properties on CD4+ T cells in vivo and in vitro. Experimental approaches to elucidate the mechanism of CD8+ T cell activation by Sp1 demonstrate in a dimeric MHC class I-Ig model that Sp1 induces CD8+ T cell activation by enhancing crosslinking of TCR. The expansion of CD8+CD28− T cells is independent, of direct antigen-presenting cell/T cell contact and, to the specificity of the T cell receptor (TCR). In CD8+CD28− T cells, Sp1 enhances Zap-70 phosphorylation and increasingly involves NF-κB which ultimately results in protection versus apoptosis and cell death and promotes survival and accumulation of the CD8+CD28− population. This is the first description of a naturally occurring bacterial antigen that is able to induce suppressive CD8+CD28− T lymphocytes in vivo and in vitro. The underlying mechanism of CD8+ T cell activation appears to rely on enhanced TCR crosslinking. The data provides evidence that ZPS of commensal bacteria play an important role in peripheral tolerance mechanisms and the maintenance of the homeostasis of the immune system

Biografieforschung: theoretische Perspektiven und methodologische Konzepte für eine re-konstruktive Geschlechterforschung

Die Biografieforschung bezeichnet einen komplexen Forschungsansatz, der auf eine lange Geschichte des wissenschaftlichen Interesses an "persönlichen Dokumenten" verweisen kann. Sie ist eine voraussetzungsvolle Forschungsperspektive, die sich in zentralen Aspekten ihres Vorgehens auf Biografien als theoretisches Konzept, als historisch-empirischen Gegenstand und als komplexe methodologische Strategie bezieht. Andere Begriffe, welche oftmals synonym gebraucht, in der Biografieforschung aber systematisch unterschieden werden, sind "Lebensgeschichte" und "Lebenslauf". Die Autorin skizziert die Perspektiven einer rekonstruktiven Geschlechterforschung innerhalb der Biografieforschung, wozu sie auf die Differenzierungen empirischer Forschung, die methodologischen Prinzipien sowie auf Datenerhebung und Datenanalyse eingeht. Sie hebt insbesondere drei Kontextrelationen bei der Interpretation eines biografischen Textes hervor: Biografie, Interaktion, kulturelle Muster und soziale Regeln. Das skizzierte Konzept von Biografieforschung begreift sie als ein offenes Programm, das vielfältige Anknüpfungspunkte zu aktuellen theoretischen Diskussionen in der Geschlechterforschung aufweist. (ICI2

Relationships of depression and anxiety symptoms with seizure frequency: Results from a multicenter follow-up study

Dehn L, Pfäfflin M, Brückner S, et al. Relationships of depression and anxiety symptoms with seizure frequency: Results from a multicenter follow-up study. Seizure. 2017;53:103-109.Purpose Depressive and anxiety disorders are frequent among people with epilepsies. There are, however, only few longitudinal studies, which examine the relationship between these comorbid psychiatric disorders and epilepsy-related variables. Thus, we investigated the interrelationships of depression and anxiety symptoms with seizure frequency across time. Methods Before admittance to an epilepsy center (T1) and six months after discharge (T2), patients (n = 198) with mainly difficult-to-treat epilepsies completed the Hospital Anxiety and Depression Scale (HADS). Correlation and path analyses were conducted. Results Depression and anxiety symptoms (HADS) as well as seizure frequency significantly decreased from baseline to follow-up. Both at T1 and T2, seizure frequency was slightly, but significantly correlated with depression and anxiety levels (rs = 0.17–.32). Cross-lagged-analyses showed that baseline (T1) level of depression significantly predicted frequency of seizures at follow-up (T2). However, anxiety at T1 was not a significant predictor of seizure frequency at T2 and seizure frequency at T1 did not predict either depressive or anxiety symptoms at T2. Conclusion The present findings emphasize the importance of psychiatric comorbidities, especially depression, for seizure frequency and its progress in patients with difficult-to-treat epilepsies referred to a specialized epilepsy center. Thus, comorbid psychiatric disorders need specific consideration as part of a comprehensive diagnostic and therapeutic treatment approach