Intratympanic steroids as a salvage therapy for severe to profound idiopathic sudden sensorineural hearing loss

Background: Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined as a decline in hearing affecting three or more frequencies by 30 dB Objective: The aim of this study was to evaluate the results of intratympanic steroids as a salvage treatment for severe ISSNHL. Materials and methods: A regimen of three IT steroid injections was offered to patients who failed a 7-days intravenous steroid treatment. Eighty-four patients underwent IT salvage treatment (IT group). Their outcomes were compared with those of 255 patients with severe ISSNHL who received the same intravenous steroid regimen without salvage IT steroid therapy (Control group). Results: 56% of the patients in the IT group had a hearing improvement of >15 dB after one month. The average hearing improvements were 26.5 ± 28 dB and 27.9 ± 24 dB in the IT group and the Control group, respectively (p ¼ .67). However, patients with a type E audiogram pattern (total deafness), displayed a substantial hearing gain. Conclusion: Intratympanic steroids failed to show a global auditory benefit as a salvage treatment in patients with severe ISSNHL. Significance: Our data suggest that a salvage treatment with intratympanic dexamethasone may be offered to patients with total deafness for whom the first systemic treatment has failed

Reins polykystiques chez le Porc

Névot Armand, Gouygou Charles, Hautefort Maurice. Reins polykystiques chez le Porc. In: Bulletin de l'Académie Vétérinaire de France tome 101 n°9, 1948. pp. 365-367

SARS-CoV-2 Causes a Different Cytokine Response Compared to Other Cytokine Storm-Causing Respiratory Viruses in Severely Ill Patients

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.</p

Targeted interplay between bacterial pathogens and host autophagy

Due to the critical role played by autophagy in pathogen clearance, pathogens have developed diverse strategies to subvert autophagy. Despite previous key findings of bacteria-autophagy interplay, a systems level insight into selective targeting by the host and autophagy modulation by the pathogens is lacking. We predicted potential interactions between human autophagy proteins and effector proteins from 56 pathogenic bacterial species by identifying bacterial proteins predicted to have recognition motifs for selective autophagy receptors p62/NDP52 and LC3. Conversely, using structure-based interaction prediction methods, we identified bacterial effector proteins that could putatively modify core autophagy components. Our analysis revealed that autophagy receptors in general potentially target mostly genus specific proteins, and not those present in multiple genera. We also show that the complementarity between the predicted p62 and NDP52 targets, which has been shown for Salmonella, Listeria and Shigella, could be observed across other pathogens. Using literature evidence, we hypothesize that this complementarity potentially leave the host more susceptible to chronic infections upon the mutation of one of the autophagy receptors. To check any bias caused by our pathogenic protein selection criteria, control analysis using proteins derived from entero-toxigenic and non-toxigenic Bacillus outer membrane vesicles indicated that autophagy targets pathogenic proteins rather than non-pathogenic ones. We also observed a pathogen specific pattern as to which autophagy phase could be modulated by specific genera. We found intriguing examples of bacterial proteins which could modulate autophagy, and in turn capable of being targeted by the autophagy receptors and LC3 as a host defence mechanism. To demonstrate the validity of our predictions, we confirmed experimentally with in vitro Salmonella invasion assays the bi-directional interactions underlying the interplay between a Salmonella protease, YhjJ and autophagy. Our comparative meta-analysis points out key commonalities and differences in how pathogens could affect autophagy and how autophagy potentially recognises these pathogenic effectors

Visual Input Is the Main Trigger and Parametric Determinant for Catch-Up Saccades During Video Head Impulse Test in Bilateral Vestibular Loss

Patients with vestibular deficit use slow eye movements or catch-up saccades (CUS) to compensate for impaired vestibulo-ocular reflex (VOR). The purpose of CUS is to bring the eyes back to the visual target. Covert CUS occur during high-velocity head rotation and overt CUS are generated after head rotation has stopped. Dynamic visual acuity is improved with an increased rate and gain of CUS. Nevertheless, the trigger and the parametric determinants of CUS are still under debate. To clarify the underlying mechanism, especially the visual contribution, we analyzed the number, amplitude and latencies of the CUS in relation with the extent of VOR deficiency. The head and eye movements were recorded in 17 patients with bilateral vestibular loss (BVL) and in 33 subjects with normal VOR gain using the Video Head Impulse Test (vHIT) in two conditions: with visible target and in darkness with an imaginary target. Our study shows that in darkness without visible target the number of CUS is significantly reduced and the relationship between the amplitude of CUS and gaze position error is lost. Results showed that there is a correlation between the number of CUS and the drop in VOR gain. CUS occurring during the head movement and when the head remained still were not always sufficiently accurate. Up to four consecutive CUS could be required to bring eyes back to the visible target. A positive correlation was found between the amplitude of overt saccades with visible target and the gaze position error, namely the remaining eye movement to reach the target. These results suggest that the visual inputs are the main trigger and parametric determinant of the CUS or at least the presence of a visual target is necessary in most cases for a CUS to occur

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

Gram-negative bacteria ubiquitously produce and release nano-size, non-replicative outer membrane vesicles (OMVs). In the gastrointestinal (GI-) tract, OMVs generated by members of the intestinal microbiota are believed to contribute to maintaining the intestinal microbial ecosystem and mediating bacteria–host interactions, including the delivery of bacterial effector molecules to host cells to modulate their physiology. Bacterial OMVs have also been found in the bloodstream although their origin and fate are unclear. Here we have investigated the interactions between OMVs produced by the major human gut commensal bacterium, Bacteroides thetaiotaomicron (Bt), with cells of the GI-tract. Using a combination of in vitro culture systems including intestinal epithelial organoids and in vivo imaging we show that intestinal epithelial cells principally acquire Bt OMVs via dynamin-dependent endocytosis followed by intracellular trafficking to LAMP-1 expressing endo-lysosomal vesicles and co-localization with the perinuclear membrane. We observed that Bt OMVs can also transmigrate through epithelial cells via a paracellular route with in vivo imaging demonstrating that within hours of oral administration Bt OMVs can be detected in systemic tissues and in particular, the liver. Our findings raise the intriguing possibility that OMVs may act as a long-distance microbiota–host communication system

Influence of Visual and Vestibular Hypersensitivity on Derealization and Depersonalization in Chronic Dizziness

Objective: The aim of this study was to investigate the relation between visual and vestibular hypersensitivity, and Depersonalization/Derealization symptoms in patients with chronic dizziness.Materials and Methods: 319 adult patients with chronic dizziness for more than 3 months (214 females and 105 males, mean age: 58 years, range: 13–90) were included in this prospective cross-sectional study. Patients underwent a complete audio-vestibular workup and 3 auto questionnaires: Hospital Anxiety and Depression (HAD), Depersonalization/Derealization Inventory (DDI), and an in-house questionnaire (Dizziness in Daily Activity, DDA) assessing 9 activities with a score ranging from 0 (no difficulty) to 10 (maximal discomfort) and 11 (avoidance) to detect patients with visual and vestibular hypersensitivity (VVH, a score &gt; 41 corresponding to mean + 1 standard deviation).Results: DDI scores were higher in case of VVH (6.9 ± 6.79, n = 55 vs. 4.2 ± 4.81, n = 256 without VVH, p &lt; 0.001, unpaired t-test), migraine (6.1 ± 6.40, n = 110 vs. 4.0 ± 4.42, n = 208no migraine, p &lt; 0.001, unpaired t-test), and motion sickness (6.8 ± 5.93, n = 41 vs. 4.4 ± 5.11, n = 277 no motion sickness, p &lt; 0.01, unpaired t-test). Women scored DDI higher than men (5.1 ± 5.42, n = 213 vs. 3.9 ± 4.91, n = 105, respectively, p &lt; 0.05, unpaired t-test). DDI scores were also related to depression and anxiety. DDI score was also higher during spells than during the basal state.Conclusion: During chronic dizziness, Depersonalization/Derealization symptoms seem to be related to anxiety and depression. Moreover, they were prominent in women, in those with visual and vestibular hypersensitivity, migraine, and motion sickness

Choice of Bacterial Growth Medium Alters the Transcriptome and Phenotype of Salmonella enterica Serovar Typhimurium

The type of bacterial culture medium is an important consideration during design of any experimental protocol. The aim of this study was to understand the impact of medium choice on bacterial gene expression and physiology by comparing the transcriptome of Salmonella enterica SL1344 after growth in the widely used LB broth or the rationally designed MOPS minimal medium. Transcriptomics showed that after growth in MOPS minimal media, compared to LB, there was increased expression of 42 genes involved in amino acid synthesis and 23 genes coding for ABC transporters. Seven flagellar genes had decreased expression after growth in MOPS minimal medium and this correlated with a decreased motility. In both MOPS minimal medium and MEM expression of genes from SPI-2 was increased and the adhesion of S. Typhimurium to intestinal epithelial cells was higher compared to the levels after growth in LB. However, SL1344 invasion was not significantly altered by growth in either MOPs minimal media or MEM. Expression of SPI-2 was also measured using chromosomal GFP reporter fusions followed by flow cytometry which showed, for the first time, that the reduction in SPI-2 transcript after growth in different media related to a reduction in the proportion of the bacterial population expressing SPI-2. These data highlight the profound differences in the global transcriptome after in vitro growth in different media and show that choice of medium should be considered carefully during experimental design, particularly when virulence related phenotypes are being measured

Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches

The epithelial lining of the small intestine consists of multiple cell types, including Paneth cells and goblet cells, that work in cohort to maintain gut health. 3D in vitro cultures of human primary epithelial cells, called organoids, have become a key model to study the functions of Paneth cells and goblet cells in normal and diseased conditions. Advances in these models include the ability to skew differentiation to particular lineages, providing a useful tool to study cell type specific function/dysfunction in the context of the epithelium. Here, we use comprehensive profiling of mRNA, microRNA and long non-coding RNA expression to confirm that Paneth cell and goblet cell enrichment of murine small intestinal organoids (enteroids) establishes a physiologically accurate model. We employ network analysis to infer the regulatory landscape altered by skewing differentiation, and using knowledge of cell type specific markers, we predict key regulators of cell type specific functions: Cebpa, Jun, Nr1d1 and Rxra specific to Paneth cells, Gfi1b and Myc specific for goblet cells and Ets1, Nr3c1 and Vdr shared between them. Links identified between these regulators and cellular phenotypes of inflammatory bowel disease (IBD) suggest that global regulatory rewiring during or after differentiation of Paneth cells and goblet cells could contribute to IBD aetiology. Future application of cell type enriched enteroids combined with the presented computational workflow can be used to disentangle multifactorial mechanisms of these cell types and propose regulators whose pharmacological targeting could be advantageous in treating IBD patients with Crohn's disease or ulcerative colitis