Is the effect of tinnitus on auditory steady-state response amplitude mediated by attention?

Objectives: Auditory steady-state response (ASSR) amplitude enhancement effects have been reported in tinnitus patients. As ASSR amplitude is also enhanced by attention, the effect of tinnitus on ASSR amplitude could be interpreted as an effect of attention mediated by tinnitus. As N1 attention effects are significantly larger than those on the ASSR, if the effect of tinnitus on ASSR amplitude were due to attention, there should be similar amplitude enhancement effects in tinnitus for the N1 component of the auditory-evoked response. Methods: MEG recordings which were previously examined for the ASSR (Diesch et al., 2010a) were analyzed with respect to the N1m component. Like the ASSR previously, the N1m was analyzed in the source domain (source space projection). Stimuli were amplitude-modulated (AM) tones with one of three carrier frequencies matching the tinnitus frequency or a surrogate frequency 1½ octave above the audiometric edge frequency in controls, the audiometric edge frequency, and a frequency below the audiometric edge. Single AM-tones were presented in a single condition and superpositions of three AM-tones differing in carrier and modulation frequency in a composite condition. Results: In the earlier ASSR study (Diesch et al., 2010a), the ASSR amplitude in tinnitus patients, but not in controls, was significantly larger in the (surrogate) tinnitus condition than in the edge condition. Patients showed less evidence than controls of reciprocal inhibition of component ASSR responses in the composite condition. In the present study, N1m amplitudes elicited by stimuli located at the audiometric edge and at the (surrogate) tinnitus frequency were smaller than N1m amplitudes elicited by sub-edge tones both in patients and controls. The relationship of the N1m response in the composite condition to the N1m response in the single condition indicated that reciprocal inhibition among component N1m responses was reduced in patients compared against controls. Conclusions: In the present study, no evidence was found for an N1-amplitude enhancement effect in tinnitus. Compared to controls, reciprocal inhibition is reduced in tinnitus patients. Thus, as there is no effect on N1m that could potentially be attributed to attention, it seems unlikely that the enhancement effect of tinnitus on ASSR amplitude could be accounted for in terms of attention induced by tinnitus

Structural changes of the corpus callosum in tinnitus

Objectives: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. Methods: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). Results: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. Conclusion: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres

Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis

Objective: Hospital-acquired pneumonia remains the most lethal and expensive nosocomial infection worldwide. Optimal therapy remains controversial. We aimed to compare mortality and clinical response outcomes in patients treated with either linezolid or vancomycin. Design: Systematic review and meta-analysis. Data sources PubMed, EMBASE, Cochrane Library, American College of Physicians Journal Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and critical care meetings were searched through April 2013. Eligibility criteria for selecting studies All randomised clinical trials comparing linezolid to vancomycin for hospital-acquired pneumonia. Data extraction Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. One author extracted the data and two authors rechecked and verified all data. Results: Nine randomised trials with a total of 4026 patients were included. The adjusted absolute mortality risk difference (RD) between linezolid and vancomycin was 0.01% (95% CI −2.1% to 2.1%; p=0.992; I2=13.5%. The adjusted absolute clinical response difference was 0.9% (95% CI −1.2% to 3.1%; p=0.409; I2=0%. The risk of both microbiological (RD=5.6%, 95% CI −2.2% to 13.3%; p=0.159; I2=0%) and methicillin-resistant Staphylococcus aureus (RD=6.4%, 95% CI −4.1% to 16.9%; p=0.230; I2=0%) eradication were not different between linezolid and vancomycin. Gastrointestinal side effects were more frequent with linezolid (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal failure, thrombocytopenia and drug discontinuation due to adverse events. Our sample size provided 99.9% statistical power to detect differences between drugs regarding clinical response and mortality. Conclusions: Linezolid and vancomycin have similar efficacy and safety profiles. The high statistical power and the near-zero efficacy difference between both antibiotics demonstrates that no drug is superior for the treatment of hospital-acquired pneumonia

Behavioral and neurophysiological correlates of emotional face processing in borderline personality disorder: are there differences between men and women?

Emotional dysregulation is a core feature of borderline personality disorder (BPD);it is, for example, known to influence one's ability to read other people's facial expressions. We investigated behavioral and neurophysiological foundations of emotional face processing in individuals with BPD and in healthy controls, taking participants' sex into account. 62 individuals with BPD (25 men, 37 women) and 49 healthy controls (20 men, 29 women) completed an emotion classification task with faces depicting blends of angry and happy expressions while the electroencephalogram was recorded. The cortical activity (late positive potential, P3/LPP) was evaluated using source modeling. Compared to healthy controls, individuals with BPD responded slower to happy but not to angry faces;further, they showed more anger ratings in happy but not in angry faces, especially in those with high ambiguity. Men had lower anger ratings than women and responded slower to angry but not happy faces. The P3/LPP was larger in healthy controls than in individuals with BPD, and larger in women than in men;moreover, women but not men produced enlarged P3/LPP responses to angry vs. happy faces. Sex did not interact with behavioral or P3/LPP-related differences between healthy controls and individuals with BPD. Together, BPD-related alterations in behavioral and P3/LPP correlates of emotional face processing exist in both men and women, supposedly without sex-related interactions. Results point to a general 'negativity bias' in women. Source modeling is well suited to investigate effects of participant and stimulus characteristics on the P3/LPP generators

VERTEBRAL OSTEOMYELITIS IS CHARACTERISED BY INCREASED RANK/OPG AND RANKL/OPG EXPRESSION RATIOS IN VERTEBRAL BODIES AND INTERVERTEBRAL DISCS

Vertebral osteomyelitis (VO) is an infection of the spine mainly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVDs) and adjacent vertebral bodies (VBs) is poorly described. The present study aimed at investigating the connection between infection and bone/disc metabolism in VO patients. 14 patients with VO (infection group) and 14 patients with burst fractures of the spine (fracture group; control) were included prospectively. Tissue biopsies from affected IVDs and adjacent VBs were analysed by RT-qPCR for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone metabolism. Most importantly, the receptor activator of NF-κB/osteoprotegerin (RANK/OPG) expression ratio was drastically elevated in both VBs and IVDs of the infection group. In parallel, expression of genes of the prostaglandin-E2-dependent prostanoid system was induced. Such genes regulate tissue degradation processes via the triad OPG/RANK/RANKL as well as via the chemokines IL-8 and CCL-20, whose expression was also found to be increased upon infection. The gene expression of the adipokine leptin, which promotes inflammatory tissue degradation, was higher in IVD tissue of the infection group, whereas the transcription of omentin and resistin genes, whose functions are largely unknown in the context of infectious diseases, was lower in infected VBs. In summary, similar expression patterns of pro-inflammatory cytokines and pro-osteoclastogenic factors were identified in VBs and IVDs of patients suffering from VO. This suggests that common immuno-metabolic pathways are involved in the mechanisms leading to tissue degradation in VBs and IVDs during VO

High-resolution analysis of c-fos chromatin accessibility using a novel DNase I-PCR assay

In our previous study, c-fos chromatin accessibility was assayed using DNase I digestion and Southern blot analysis. This low-resolution mapping of c-fos chromatin accessibility demonstrated that serum stimulation of the c-fos enhancer induces a reversivle increase in c-fos DNase I sensitivity and suggested that a 5' to 3' gradient of DNase I sensitivity may form downstream from the c-fos enhancer. To confirm the existence of a 5' to 3' gradient of accessibility, we have recently developed a high-resolution polymerase chain reaction (PCR) assay for DNase I sensitivity. Using this novel DNase I assay, we have reliably detected position- and time-dependent gradients of chromatin accessibility around the c-fos enhancer. These data confirm our earlier results and further support the hypothesis that the changes in c-fos chromatin accessibility originate near the 5' enhancer. As a technique for future examinations of gene structure, our data demonstrate the value of the DNase I-PCR assay for rapidly preparing comprehensive and high-resolution maps of chromatin accessibility for any sequenced genomic region.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30107/1/0000479.pd

Advanced Preparation Makes Research in Emergencies and Isolation Care Possible: The Case of Novel Coronavirus Disease (COVID-19)

The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high-quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the first use of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance of research in any emergency, when facing any threat

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.Peer reviewe

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)