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Recent breakthroughs in our understanding of sensorineural hearing loss etiology have encouraged the identification of novel hearing therapeutics, paving the way for precision hearing medicine. Critical to this field is the curation of health resources on hearing data. A systematic review of the literature was conducted to map existing (inter)national and regional datasets that include hearing data to inform the development of future hearing repositories. Systematic literature review was performed adhering to Preferred Reporting Items for Systematic Review and MetaAnalysis recommendations. Databases, including those from gray literature, were searched to identify publications reporting on phenotypic and/ or genotypic hearing data in May 2019. The databases reviewed were Medline, PubMed, Embase databases, and Google Scholar. Publications on local datasets were excluded. All hearing datasets identified in the screening process were noted. For each dataset, geography, context, objective, period of time run, numbers and demographics of participants, genomic data, hearing measures and instruments used were extracted and cataloged. One hundred and eighty-eight datasets were identified, containing hearing data on populations ranging from 100 to 1.39 million individuals, and all extracted data have been cataloged. This searchable resource has been made accessible online. This unique catalog provides an overview of existing datasets that contain valuable information on hearing. This can be used to inform the development of national and international patient data repositories for hearing loss and guide strategic collaboration between key stakeholder groups, pivotal to the delivery and development of sensorineural hearing loss precision diagnostics and treatments.

Posterior reversible encephalopathy syndrome (PRES) is a rare disorder with multiple causes but potentially caused by chemotherapy. We present 3 cases of PRES of whom 2 are presumably caused by oxaliplatin and one by regorafenib. We discuss in this article the 3 cases individually and we summarize in the discussion the proposed theories in the literature of possible pathophysiological mechanisms. Our main goal of this article is to increase awareness among physicians when they are confronted with patients on chemotherapy who present with (sub)acute encephalopathy., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

During spaceflight, astronauts face radiations, mechanical, and socio-environmental stressors. To determine the impact of chronic socio-environmental stressors on immunity, we exposed adult male mice to chronic unpredictable mild psychosocial and environmental stressors (CUMS model) for 3 weeks. This duration was chosen to simulate a long flight at the human scale. Our data show that this combination of stressors induces an increase of serum IgA, a reduction of normalized splenic mass and tends to reduce the production of pro-inflammatory cytokines, as previously reported during or after space missions. However, CUMS did not modify major splenic lymphocyte sub-populations and the proliferative responses of splenocytes suggesting that these changes could be due to other factors such as gravity changes. Thus, CUMS, which is an easy to implement model, could contribute to deepen our understanding of some spaceflight-associated immune alterations and could be useful to test countermeasures.

Background: Knowledge of the role of intravenous iron without the use of additional erythropoietic stimulating agents in anemic cancer patients is limited. This study evaluated the effect of ferric carboxymaltose (FCM) in a group of digestive oncology (DIO) patients and aimed to differentiate therapy response according to different types of iron deficiency (ID) anemia., Methods: In this retrospective study, we identified DIO patients who were receiving FCM and had eligible baseline and follow-up hemoglobin (Hb) levels that did not require red blood cell transfusion. Subgroup analyses examined adequately versus inadequately treated patients and low (<100 µg/L) vs. high (>100 µg/L) baseline ferritin levels. Inadequate treatment was defined as administration of an insufficient dose of FCM, based on the modified Ganzoni formula., Results: A total of 414 patients were receiving FCM, of whom 41 were excluded because of transfusion and another 70 because of unknown or inadequate baseline iron status. Thus, the study group consisted of 303 patients. Follow-up serum levels were evaluated after a median of 4 weeks. Overall, the median change between baseline and follow-up Hb was 0.5 (interquartile range [IQR]: -0.1-1.6) g/dL. No significant difference in this change was found between the adequately and inadequately dosed groups. The median change in Hb was significantly greater in the low baseline ferritin group than in the high baseline ferritin group: 1.2 (IQR: 0.3-2.2) vs. 0.4 (IQR: -0.3-1.4) g/dL, respectively; P=0.004., Conclusions: Intravenous administration of iron in DIO patients with ID anemia leads to a significant increase in Hb. Moreover, differentiating between the types of ID anemia based on ferritin levels could be applied to predict therapy response, although better biomarkers are needed., Competing Interests: Conflict of Interest: Hans Prenen has received speaker fees from Vfor Pharma. Marc Ferrante has received personal fees and/or non-financial support from Takeda, Abbvie, Boehringer-Ingelheim, Chiesi, Falk, Ferring, Janssen, Mitsubishi Tanabe, MSD, Tillotts and Zeria. The other authors disclose no conflict of interest. The authors have full control of all primary data and agree to allow the journal to review their data if requested

Acute or chronic administrations of high doses of ethanol in mice are known to produce severe cognitive deficits linked to hippocampal damage. However, we recently reported that chronic and moderate ethanol intake in C57BL/6J mice induced chromatin remodeling within the Bdnf promoters, leading to both enhanced brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis under free-choice protocol. We performed here a series of cellular and behavioral studies to analyze the consequences of these modifications. We showed that a 3-week chronic free-choice ethanol consumption in C57BL/6J mice led to a decrease in DNA methylation of the Bdnf gene within the CA1 and CA3 subfields of the hippocampus, and upregulated hippocampal BDNF signaling pathways mediated by ERK, AKT and CREB. However, this activation did not affect long-term potentiation in the CA1. Conversely, ethanol intake impaired learning and memory capacities analyzed in the contextual fear conditioning test and the novel object recognition task. In addition, ethanol increased behavioral perseveration in the Barnes maze test but did not alter the mouse overall spatial capacities. These data suggested that in conditions of chronic and moderate ethanol intake, the chromatin remodeling leading to BDNF signaling upregulation is probably an adaptive process, engaged via epigenetic regulations, to counteract the cognitive deficits induced by ethanol.

High ethanol intake is well known to induce both anxiolytic and anxiogenic effects, in correlation with chromatin remodeling in the amygdaloid brain region and deficits in cell proliferation and survival in the hippocampus of rodents. Whether only moderate but chronic ethanol intake in C57BL/6J mice could also have an impact on chromatin remodeling and neuroplasticity was addressed here. Chronic ethanol consumption in a free choice paradigm was found to induce marked changes in the expression of genes implicated in neural development and histone post-translational modifications in the mouse hippocampus. Transcripts encoding neural bHLH activators and those from Bdnf exons II, III and VI were upregulated, whereas those from Bdnf exon VIII and Hdacs were downregulated by ethanol compared with water consumption. These ethanol-induced changes were associated with enrichment in both acetylated H3 at Bdnf promoter PVI and trimethylated H3 at PII and PIII. Conversely, acetylated H3 at PIII and PVIII and trimethylated H3 at PVIII were decreased in ethanol-exposed mice. In parallel, hippocampal brain-derived neurotrophic factor (BDNF) levels and TrkB-mediated neurogenesis in the dentate gyrus were significantly enhanced by ethanol consumption. These results suggest that, in C57BL/6J mice, chronic and moderate ethanol intake produces marked epigenetic changes underlying BDNF overexpression and downstream hippocampal neurogenesis.

Stress-induced alterations in neuronal plasticity and in hippocampal functions have been suggested to be involved in the development of mood disorders. In this context, we investigated in the hippocampus the activation of intracellular signaling cascades, the expression of epigenetic markers and plasticity-related genes in a mouse model of stress-induced hyperactivity and of mixed affective disorders. We also determined whether the antidepressant drug agomelatine, a MT1/MT2 melatonergic receptor agonist/5-HT2C receptor antagonist, could prevent some neurobiological and behavioral alterations produced by stress. C57BL/6J mice, exposed for 3 weeks to daily unpredictable socio-environmental stressors of mild intensity, were treated during the whole procedure with agomelatine (50 mg kg(-1) per day, intraperitoneal). Stressed mice displayed robust increases in emotional arousal, vigilance and motor activity, together with a reward deficit and a reduction in anxiety-like behavior. Neurobiological investigations showed an increased phosphorylation of intracellular signaling proteins, including Atf1, Creb and p38, in the hippocampus of stressed mice. Decreased hippocampal level of the repressive epigenetic marks HDAC2 and H3K9me2, as well as increased level of the permissive mark H3K9/14ac suggested that chronic mild stress was associated with increased gene transcription, and clear-cut evidence was further indicated by changes in neuroplasticity-related genes, including Arc, Bcl2, Bdnf, Gdnf, Igf1 and Neurod1. Together with other findings, the present data suggest that chronic ultra-mild stress can model the hyperactivity or psychomotor agitation, as well as the mixed affective behaviors often observed during the manic state of bipolar disorder patients. Interestingly, agomelatine could normalize both the behavioral and the molecular alterations induced by stress, providing further insights into the mechanism of action of this new generation antidepressant drug.

The present study was aimed at analyzing the effects of physical exercise on mitochondrial physiology, anxio-depressive-like behaviors and neuroplasticity in mice. Adult C57BL/6J male mice were isolated in home cages equipped or not with free-running wheels. After 6weeks of exercise, mice were tested in various behavioral paradigms to evaluate anxiety- and depressive-like behaviors. The hippocampi were dissected for neurochemical assays, including mitochondrial activity, monoamines content and the expression of genes involved in energy metabolism and brain-derived neurotrophic factor (BDNF) regulation. Exercise decreased anxiety-like behaviors in the open field and elevated plus maze, and exerted antidepressant-like effects in the tail suspension test. Exercise stimulated brain mitochondrial activity and increased resistance against rotenone, an inhibitor of complex I activity. Furthermore, mRNA expression of Bdnf, Gdnf, Tfam (mitochondrial transcription factor A), and Ndufa6 (mitochondrial I subunit) genes, as well as the phosphorylation of cAMP response element-binding protein were increased after exercise. In summary, exercise appears to engage mitochondrial pathways and to potentiate neuroplasticity and might be associated to mood improvement., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Endoscopy has been the gold standard for diagnosing and following patients with inflammatory bowel disease. However, ileocolonoscopy is still an expensive and invasive method. Secondly we do know that clinical scores for ulcerative colitis and Crohn's disease are subjective which creates several problems. And thirdly, when using the known serological markers such as C-reactive protein, white blood cell count en albumin, one should take into account that these markers are not perfect or superior to the current diagnostic techniques given their low sensitivity and specificity. Fecal markers may prove to have a greater specificity. Calprotectin can differentiate between active and inactive inflammatory bowel disease and between inflammatory bowel disease and irritable bowel syndrome. It correlates with the severity of symptoms and it may predict relapse especially in ulcerative colitis. Finally it can be used as a surrogate marker for the endoscopic response during treatment given a normal value of calprotectin is a reliable marker for mucosal healing. Lactoferrin also seems to be a sensitive and specific marker for the detection of chronic inflammation and for predicting relapse. The relationship with the endoscopic activity is significant and lactoferrin values are significantly higher in active endoscopic disease as compared to inactive disease. Finally, given the significant correlation with endoscopic activity, lactoferrin can function as an adequate marker for the monitoring of therapy.

CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.