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Objective To review current information about diagnosis and management of tinnitus aiming to identify opportunities for achieving a cost-effective, efficient, evidence-based approach that meets the needs of tinnitus sufferers. Data Sources PubMed/MEDLINE. Review Methods In total, 249 relevant published reports were reviewed. Pertinent keywords and MeSH terms identified reports via PubMed and EMBASE. Acknowledged experts were consulted on ways to improve tinnitus management. Conclusions There may be opportunities to improve evaluation and management of patients with tinnitus using modern modes of communication and a multidisciplinary therapeutic approach. Implications for Practice Tinnitus can adversely affect quality of life while being time-consuming and costly to evaluate and manage. Based on both personal experience and the reports of others, patients with tinnitus who choose to see a physician primarily want to know two things: (1) that the tinnitus that is so distressing will not remain at the same level of severity forever and (2) that something can be done to help cope with the tinnitus that is so annoying. Recent advancements in internet communications, social media, information technology, artificial intelligence, machine learning, holistic medical care, mind-body integrative health care, and multidisciplinary approaches in medical therapeutics may be possibly making new ways of meeting the needs of patients with tinnitus.

Introduction & Hypothesis: Diffusion-weighted imaging (DWI), a technique sensitive to acute brain ischemia, may hold utility in predicting neurological outcome in comatose post-cardiac arrest patients. Outcome studies are biased by early withdrawal of life sustaining therapy (WLST), leading to a self-fulfilling prophecy. This creates a need to reassess the use of DWI as a neuroprognostic tool in patients who have not undergone WLST. We hypothesize that DWI abnormalities is a robust predictor of poor neurological outcome in our WLST - controlled cohort. Methods: We leveraged the MOCHA database, a registry of over 300 comatose post-cardiac arrest patients, to retrospectively examine neurological outcomes in a cohort of patients who did not undergo WLST. A good outcome was defined by a cerebral performance category (CPC) score at discharge of 1 - 3, while a poor outcome CPC 4 - 5 (n=43). We first examined the relationship between the number of brain regions with DWI abnormalities and CPC score using a linear regression. We then examined how DWI abnormalities in specific brain regions correlated with CPC score outcome groups using a fisher exact test. DWI abnormalities were qualitatively determined by two vascular neurologists. Results: We found a positive correlation between the number of brain regions with DWI abnormalities and CPC score ( linear regression , R 2 =0.572, p=2.670x10 -9 ). Interestingly, the association between DWI abnormalities and CPC score exhibited brain region-specific variability. DWI abnormalities exhibited the strongest association with poor neurological outcome in the occipital lobe ( fisher exact test , p=7.413x10 -10 ), parietal lobe (p=9.125x10 -9 ), frontal lobe (p=5.385x10 -9 ), temporal lobe (p=3.904x10 -8 ) and basal ganglia (p=2.342x10 -7 ); and the weakest association in the white matter (p=1.000) and brain stem (p=6.612x10 -2 ). Conclusion: Our preliminary results suggest that the region of ischemia is an important factor to consider in predicting neurological outcome. This warrants a larger scale WLST-controlled study examining region-specific DWI abnormalities and neurological outcome - the findings of which would improve our neuroprognostication capabilities in comatose post-cardiac arrest patients.

Yellow fever mosquitoes, Aedes aegypti, face diverse salt and water challenges. Larvae lose salt to the freshwater environment and gain water osmotically, whereas adults tend to lose water by evaporation. Moreover, adult females take in large quantities of salt and water during a blood meal. We hypothesize that sodium‐dependent cation‐chloride cotransporters (CCCs) contribute to the salt and water balance of Aedes aegypti by participating in epithelial salt secretion and absorption. Sequence analysis revealed three genes (AAEL006180, AAEL009888, and AAEL009886) in Aedes aegypti with similarity to vertebrate Na‐K‐Cl cotransporters. We performed multiple sequence alignment and phylogenetic analysis of the proteins encoded by the Aedes aegypti genes and orthologs in Culex and Anopheles mosquitoes, Drosophila, and other arthropods. The protein encoded by AAEL006180 groups in a clade with the human secretory Na‐K‐Cl cotransporter and a Drosophila cotransporter known to be involved in salt secretion. In contrast, AAEL009888 and AAEL009886 fall into a clade that includes sequences from other insects but not vertebrates. Moreover, both AAEL009888 and AAEL009886 have orthologs in other mosquito genera but other insects only have one ortholog, indicating that AAEL009888 and AAEL009886 probably diverged early in the evolution of mosquitoes. Amino acids that differ among the paralogs include residues known to influence ion and inhibitor binding affinities. Using qPCR, we quantified the relative gene expression of the Aedes aegypti paralogs with at least two isoform‐specific primer sets for each gene. AAEL009886 transcript is expressed at significantly greater levels in larvae compared to adults and at significantly greater levels in anal papillae compared to Malpighian tubules, suggesting that AAEL009886 may be specialized for ion absorption in larvae. In contrast, AAEL006180 and AAEL009888 transcripts are expressed at approximately the same levels in adults and larvae. To evaluate the physiological role of the proteins encoded by AAEL006180 and AAEL009888, we attempted to reduce expression of each transporter using dsRNA. Larvae exposed to dsRNA corresponding to either transporter had up to five‐fold increases in hemolymph ammonium levels compared to negative controls as well as smaller changes in other hemolymph cations. Our results point towards physiological roles for AAEL006180 and AAEL009888 in osmoregulation and ammonia balance of larval mosquitoes.Support or Funding InformationNSF‐IOS‐1557230