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Background: Extrusion of electrodes outside the cochlea and tip fold overs may lead to suboptimal outcomes in cochlear implant (CI) recipients. Intraoperative measures such as Trans-Impedance Matrix (TIM) measurements may enable clinicians to identify electrode malposition and direct surgeons to correctly place the electrode array during surgery., Objectives: To assess the current literature on the effectiveness of TIM measurements in identifying extracochlear electrodes and tip fold overs., Methods: A scoping review of studies on TIM-based measurements were carried out using the Databases-Medline/PubMed, AMED, EMBASE, CINAHL and the Cochrane Library following PRISMA guidelines. Eleven full texts articles met the inclusion criteria. Only human studies pertaining to TIM as a tool used in CI were included in the review. Further, patient characteristics, electrode design, and TIM measurement outcomes were reported., Results: TIM measurements were available for 550 implanted ears with the subjects age ranged between 9 months to 89 years. Abnormal TIM measurements were reported for 6.55% (36). Tip fold over was detected in 3.64% (20) of the cases, extracochlear electrodes in 1.45% (8), and 1.45% (8) were reported as buckling. Slim-modiolar electrode array designs were more common (54.71%) than pre-curved (23.34%) or lateral wall (21.95%) electrode array. Abnormal cochlear anatomy was reported for five ears (0.89%), with normal cochlear anatomy for all other patients., Conclusion: TIM measurement is a promising tool for the intraoperative detection of electrode malposition. TIM measurement has a potential to replace intraoperative imaging in future. Though, TIM measurement is in its early stages of clinical utility, intuitive normative data sets coupled with standardised criteria for detection of abnormal electrode positioning would enhance its sensitivity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ayas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear., Aim: To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients., Methods: We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity ( I 2 ) were estimated using Review Manager version 5.3., Results: From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I 2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I 2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I 2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients., Conclusion: Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients., Competing Interests: Conflict-of-interest statement: Dr. Wong YJ was an invited speaker for Gilead Science. Other authors have no conflict of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The increasing number of reports on cutaneous reactions following COVID-19 vaccination has led to growing concerns among certain groups., Objective: We reviewed the published reports of cutaneous lesions after COVID-19 vaccination., Methods: We conducted a literature search for original and review articles published between January 1, 2020, and September 27, 2021., Results: Eleven cutaneous reactions associated with COVID-19 vaccines were determined; the most prevalent reactions were local injection site reactions, delayed local reactions, urticaria, angioedema, and morbilliform eruptions. There were more reports on skin reactions following the administration of messenger RNA-based vaccines than on those following the administration of adenoviral vector or inactivated whole-virus vaccines, in part, due to their higher administration rate. Most reported skin reactions occurred after the first vaccine dose., Limitations: A reporting bias could not be excluded, and skin biopsy results were not available for most included individuals. Moreover, given that the included trials focused on vaccine efficacy, there was a lack of details concerning cutaneous reactions and participant information., Conclusion: Not all cutaneous reactions observed after COVID-19 vaccination are hypersensitivity reactions. Different cutaneous reactions may reflect underlying immune responses to the vaccines. A large majority of COVID-19 vaccination reactions were mild and self-limiting, and people should be encouraged to complete their vaccination regimen., Competing Interests: None disclosed., (© 2022 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Background: Occupational dermatoses caused by personal protective equipment (PPE) in the ongoing COVID-19 pandemic are emerging occupational health challenges that must be promptly and effectively addressed to ease burden on our health care workers., Objective: A systematic review was conducted to determine common PPE-related dermatoses, affected body sites, and implicated occupational contactants. We further proposed solutions to mitigate this problem., Methods: Online databases were searched for articles on PPE-related dermatoses in health care workers during the COVID-19 pandemic written in English and published from January 1, 2020, to January 30, 2021., Results: Sixteen studies, including a total of 3958 participants, were included. The most common dermatoses were xerosis, pressure-related erythema, and contact dermatitis, mainly affecting the face and hands. The most widely implicated contactants were increased frequency of hand hygiene, gloves, N95 masks, and goggles. Proposed solutions were categorized as individual self-care, protection of the workforce, and long-term preventive measures., Conclusion: Through measures such as regular basic skin care education, early access to specialty clinics via telemedicine, and designing of better-fit PPE, the challenges posed by PPE-related occupational dermatoses can be significantly reduced., Competing Interests: None disclosed., (© 2021 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Cochlear implants restore hearing in patients with severe to profound deafness by delivering electrical stimuli inside the cochlea. Understanding stimulus current spread, and how it correlates to patient-dependent factors, is hampered by the poor accessibility of the inner ear and by the lack of clinically-relevant in vitro, in vivo or in silico models. Here, we present 3D printing-neural network co-modelling for interpreting electric field imaging profiles of cochlear implant patients. With tuneable electro-anatomy, the 3D printed cochleae can replicate clinical scenarios of electric field imaging profiles at the off-stimuli positions. The co-modelling framework demonstrated autonomous and robust predictions of patient profiles or cochlear geometry, unfolded the electro-anatomical factors causing current spread, assisted on-demand printing for implant testing, and inferred patients' in vivo cochlear tissue resistivity (estimated mean = 6.6 kΩcm). We anticipate our framework will facilitate physical modelling and digital twin innovations for neuromodulation implants., (© 2021. The Author(s).)

Objective: Because of the increasing emergence of skin manifestations of COVID-19 worldwide, we investigated the published reports of these lesions., Methods: We conducted a literature search for original and review articles published from November 11, 2019 to September 30, 2020., Results: We identified 5 skin lesions common in patients with COVID-19: pseudo-chilblains, rashes containing macules and papules, and urticarial, vesicular, and vaso-occlusive lesions. These lesions manifested at various times in relation to the COVID-19 symptoms, which may indicate whether the lesions are virus-induced or are delayed immunological responses to the infection. Skin lesions were more prevalent among Europeans and United States residents than among Asians, as was pseudo-chilblain, and the morphology of the skin lesions varied among continents. Pseudo-chilblains were the most common COVID-19 skin manifestation in Europe and the United States, but there was only 1 reported case from Asian populations. Additionally, patients with vaso-occlusive lesions were more likely than those with pseudo-chilblains to be admitted to the intensive care unit and to die., Conclusion: Different cutaneous manifestations in patients with COVID-19 could reflect a wide spectrum of viral interactions with the skin, though reporting bias may play a role as well., Competing Interests: None disclosed., (© 2020 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

We identified DNA methylation targets specific for urothelial cancer (UC) by genome-wide methylation difference analysis of human urothelial (RT4, J82, 5637), prostate (LNCAP, DU-145, PC3) and renal (RCC-KP, CAKI-2, CAL-54) cancer cell lines with their respective primary epithelial cells. A large overlap of differentially methylated targets between all organs was observed and 40 Cytosine-phosphate-Guanine motifs (CpGs) were only specific for UC cells. Of those sites, two also showed high methylation differences (≥47%) in vivo when we further compared our data to those previously obtained in our array-based analyses of urine samples in 12 UC patients and 12 controls. Using mass spectrometry, we finally assessed seven CpG sites in this "bladder-specific" region of interest in urine samples of patients with urothelial ( n = 293), prostate ( n = 75) and renal ( n = 23) cancer, and 143 controls. DNA methylation was significantly increased in UC compared to non-UC individuals. The differences were more pronounced for males rather than females. Male UC cases could be distinguished from non-UC individuals with >30% sensitivity at 95% specificity (Area under the curve (AUC) 0.85). In summary, methylation sites highly specific in UC cell lines were also specific in urine samples of UC patients showing that in-vitro data can be successfully used to identify biomarker candidates of in-vivo relevance.

Here, we discovered TGFBI as a new urinary biomarker for muscle invasive and high-grade urothelial carcinoma (UC). After biomarker identification using antibody arrays, results were verified in urine samples from a study population consisting of 303 patients with UC, and 128 urological and 58 population controls. The analyses of possible modifying factors (age, sex, smoking status, urinary leukocytes and erythrocytes, and history of UC) were calculated by multiple logistic regression. Additionally, we performed knockdown experiments with TGFBI siRNA in bladder cancer cells and investigated the effects on proliferation and migration by wound closure assays and BrdU cell cycle analysis. TGFBI concentrations in urine are generally increased in patients with UC when compared to urological and population controls (1321.0 versus 701.3 and 475.6 pg/mg creatinine, respectively). However, significantly increased TGFBI was predominantly found in muscle invasive (14,411.7 pg/mg creatinine), high-grade (8190.7 pg/mg) and de novo UC (1856.7 pg/mg; all p < 0.0001). Knockdown experiments in vitro led to a significant decline of cell proliferation and migration. In summary, our results suggest a critical role of TGFBI in UC tumorigenesis and particularly in high-risk UC patients with poor prognosis and an elevated risk of progression on the molecular level.

A series of experiments investigated potential changes in temporal processing during the months following activation of a cochlear implant (CI) and as a function of stimulus level. Experiment 1 tested patients on the day of implant activation and 2 and 6 months later. All stimuli were presented using direct stimulation of a single apical electrode. The dependent variables were rate discrimination ratios (RDRs) for pulse trains with rates centred on 120 pulses per second (pps), obtained using an adaptive procedure, and a measure of the upper limit of temporal pitch, obtained using a pitch-ranking procedure. All stimuli were presented at their most comfortable level (MCL). RDRs decreased from 1.23 to 1.16 and the upper limit increased from 357 to 485 pps from 0 to 2 months post-activation, with no overall change from 2 to 6 months. Because MCLs and hence the testing level increased across sessions, two further experiments investigated whether the performance changes observed across sessions could be due to level differences. Experiment 2 re-tested a subset of subjects at 9 months post-activation, using current levels similar to those used at 0 months. Although the stimuli sounded softer, some subjects showed lower RDRs and/or higher upper limits at this re-test. Experiment 3 measured RDRs and the upper limit for a separate group of subjects at levels equal to 60 %, 80 % and 100 % of the dynamic range. RDRs decreased with increasing level. The upper limit increased with increasing level for most subjects, with two notable exceptions. Implications of the results for temporal plasticity are discussed, along with possible influences of the effects of level and of across-session learning.

Information on biomarkers of urothelial carcinomas (UC) for clinical decision-making is limited. Here, we newly identified and verified CXCL16 as a promising novel biomarker in urine for high grade and muscle invasive UC in a cross-sectional cohort of 308 UC patients, 126 urological hospital controls, and 50 population controls using antibody arrays and ELISA. Median CXCL16 levels in urine was significantly higher in UC patients (273.2 pg/mg creatinine) compared to hospital (148.1 pg/mg) and population controls (85.1 pg/mg) with a particular preference for high grade (460.8 pg/mg), muscle invasive (535.7 pg/mg) and primary UC (327.8 pg/mg) (all p<0.0001). Group differences were confirmed after adjusting or stratifying for potential clinical and individual characteristics, such as leukocyte counts, haematuria, age, gender, and smoking status. In contrast, CXCL16 showed less discriminating power in low grade (244.3 pg/mg), non-muscle invasive (≤pT1, 251.2 pg/mg) and recurrent UC (203.9 pg/mg). In agreement with its function in immune defence, expression of CXCL16 in tissue samples of primary UC patients (n=53) showed only a weak or no immunoreactivity compared to urological hospital controls (n=32). Expression of CXCR6, the G-protein-coupled receptor of CXCL16, remained unchanged. Our findings suggest that evading the immune defence by shedding cell-surface CXCL16 and its increased elimination in urine is a molecular feature of high grade and muscle invasive UC. Therefore, urinary CXCL16 may serve as a useful, simple and non-invasive tool to identify high-risk UC with increased risk of progression at the molecular level., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objective: To assess published hand hygiene behavioral interventions that employed a social marketing framework and to recommend improvements to future interventions., Methods: We performed a systematic literature review by searching the PubMed database and the Cumulative Index to Nursing and Allied Health Literature for published articles about hand hygiene behavioral interventions in healthcare facilities, schools, and community settings. Our analysis included articles that describe multifaceted interventions and evaluated them with predefined social marketing benchmark criteria., Results: Of 53 interventions analyzed in this review, 16 (30.2%) employed primary formative audience research, 5 (9.4%) incorporated social or behavioral theories, 27 (50.9%) employed segmentation and targeting of the audience, 44 (83.0%) used components of the "marketing mix," 3 (5.7%) considered the influence of competing behaviors, 7 (13.2%) cultivated relationships with the target audience, and 15 (28.3%) provided simple behavioral messages. Thirty-five (66.0%) of the interventions demonstrated a significant improvement in performance, but only 21 (39.6%) were considered to have a strong evaluative design. The median duration of the interventions was 8.0 months., Conclusions: From a social marketing perspective, the promotion of hand hygiene could be improved in several ways. The effectiveness of social marketing in hand hygiene promotion should be tested in future interventions.

Hyaluronidase was purified to apparent homogeneity from the spent medium of Peptostreptococcus sp. strain 84H14S. The enzyme was purified 310-fold by ethanol precipitation, gel chromatography, and cation-exchange chromatography with a recovery of 42% of the original activity in the culture medium. The molecular weight of the purified enzyme was estimated to be 160,000 by gel filtration with Sephacryl S-300. Like bacterial mucopolysaccharidases of other sources, the enzyme carried out an eliminative reaction with the substrate, producing 4,5-unsaturated disaccharides as the final end products. Its optimum temperature of activity is 46 degrees C. The purified peptostreptococcal hyaluronidase was different from previously reported bacterial hyaluronidases in several respects. It degraded hyaluronic acid rapidly and also exhibited some activity against chondroitin sulfate A and chondroitin sulfate C. The KmS for hyaluronic acid, chondroitin sulfate A, and chondroitin sulfate C were 0.14, 1.4, and 2.6 mg/ml, respectively. The specific activity of hyaluronidase was much higher than that of any previously purified mucopolysaccharidases. The Vmax against hyaluronic acid reached 400 mmol of product per min per mg of protein at 22 degrees C. The peptostreptococcal hyaluronidase was also unique in that its optimum pH of activity was around neutrality, whereas other bacterial hyaluronidases were most active at acidic pHs.