Establishing multifactorial risk factors for adult-onset hearing loss: A systematic review with topic modelling and synthesis of epidemiological evidence.

BACKGROUND: This systematic review explores the multifaceted nature of risk factors contributing to adult-onset HL. The objective was to synthesise the most recent epidemiological evidence to generate pooled proportional incidences for the identified risk factors. METHODS: We conducted an extensive search of electronic databases (MEDLINE, EMBASE, and psychINFO) for studies providing epidemiological evidence of risk factors associated with hearing loss. Topic modelling using Latent Dirichlet Allocation (LDA) was first conducted to determine how many risk factor themes were available from the papers. Data were analysed by calculating the pooled proportional incidence using a meta-analysis of proportions. RESULTS: From the 72 studies reviewed, six key risk factor themes emerged through LDA topic modelling. The review identified ototoxicity, primarily caused by cancer treatments and antibiotics, infectious diseases like COVID-19, occupational noise exposure, lifestyle factors, health conditions, biological responses, and age progression as significant risk factors for HL. The highest proportional incidence was found with cancer-related ototoxicity at 55.4% (95%CI: 39.0-70.7), followed closely by ototoxicity from infectious diseases at 50.0% (95%CI: 28.5-71.5). This high proportional incidence suggests the need to explore less destructive therapies and proactively monitor hearing function during treatments. CONCLUSIONS: The findings of this review, combined with the synthesis of epidemiological evidence, enhance our understanding of hearing loss (HL) pathogenesis and highlight potential areas for intervention, thereby paving the way for more effective prevention and management of adult-onset hearing loss in our ageing global population.

The Benefits of Cochlear Implantation for Adults: A Systematic Umbrella Review.

OBJECTIVES: The uptake of cochlear implants among adults who could benefit (based on pure-tone audiometry) in developed countries is estimated to be less than 10%. Concerns about potential surgical complications, fear of losing residual hearing, and limited awareness about the benefits of this intervention contribute to the low adoption rate. To enhance quality of life and improve the uptake of cochlear implants, it is essential to have a clear understanding of their benefits. DESIGN: This umbrella review aims to summarize the major benefits of cochlear implant usage in adults, by synthesizing findings from published review articles. A comprehensive search of databases including MEDLINE, EMBASE, PsycINFO, and Google Scholar, was conducted. The search was limited to English-language review articles published between 1990 and 2022, focusing on cochlear implant outcomes in at least 5 adults (aged ≥18 years). Two independent reviewers screened titles, abstracts, and full-text articles, and conducted a quality assessment using the Joanna Briggs Checklist for Systematic Reviews and Research Syntheses. RESULTS: Forty-two articles were included in this review. There were 15 systematic reviews with meta-analysis, 25 systematic reviews without meta-analysis, and 2 systematic scoping reviews. All 42 articles underwent quality assessment using the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses, of which 40% (n = 17) satisfied 9 out of 11 quality criteria. This umbrella review shows that cochlear implants are associated with improvements in speech perception and recognition as well as improved quality of life and cognition. These benefits are observed in a significant proportion of adults undergoing the procedure, highlighting its effectiveness as a viable intervention for individuals with severe to profound hearing loss. CONCLUSIONS: The potential benefits of cochlear implantation appear to outweigh the risks and complications associated with the procedure. It is recommended that adults with severe to profound hearing loss in particular, engage in informed discussions with healthcare professionals to consider cochlear implantation as a viable treatment option.

Trends in Time in Range-Related Publications and Clinical Trials: A Bibliometric Review.

Objective: The goal of this article was to describe trends in publications (including conference abstracts) and clinical trials that report on glycemic time in range (TIR). Data sources: Reviewed databases included but were not limited to MEDLINE and Embase. Clinical trial registries were also sourced. Study selection: All studies reporting TIR published between 2010 and 2021 were included. Clinical trials reporting TIR that started in or after 2010 were also included. Non-English publications, abstracts, and clinical trials were excluded. Book chapters, nonhuman studies, and studies not reporting TIR were excluded. Data extraction: Manuscript/abstract category, publication year, study region, interventional versus observational role of continuous glucose monitoring (CGM), and clinical trial start and completion dates were captured. Glycemic outcomes reported in publications or trials, including TIR as a primary outcome, A1C, time below range (TBR), and time above range (TAR), were also captured. Results: A total of 373 clinical trials, 531 publications, and 620 abstracts were included in the review. The number of trials, publications, and abstracts reporting TIR significantly increased, particularly between 2018 and 2021, during which time the number of clinical trials, publications, and conference abstracts reporting TIR increased by 6-fold, 12-fold, and 4.5-fold, respectively. About 35-44% of studies reported TIR as a primary outcome. Approximately 54% of clinical trials, 47% of publications, and 47% of conference abstracts reported the role of CGM to be observational. TBR was reported more often than TAR. Conclusion: The marked increase in the number of trials, publications, and abstracts reporting TIR highlights the increasing significance and acceptance of TIR as an outcome measure in diabetes management.

An Exploratory EEG Analysis on the Effects of Virtual Reality in People with Neuropathic Pain Following Spinal Cord Injury.

Neuropathic pain in people with spinal cord injury is thought to be due to altered central neuronal activity. A novel therapeutic intervention using virtual reality (VR) head-mounted devices was investigated in this study for pain relief. Given the potential links to neuronal activity, the aim of the current study was to determine whether use of VR was associated with corresponding changes in electroencephalography (EEG) patterns linked to the presence of neuropathic pain. Using a within-subject, randomised cross-over pilot trial, we compared EEG activity for three conditions: no task eyes open state, 2D screen task and 3D VR task. We found an increase in delta activity in frontal regions for 3D VR with a decrease in theta activity. There was also a consistent decrease in relative alpha band (8-12 Hz) and an increase in low gamma (30-45 Hz) power during 2D screen and 3D VR corresponding, with reduced self-reported pain. Using the nonlinear and non-oscillatory method of extracting fractal dimensions, we found increases in brain complexity during 2D screen and 3D VR. We successfully classified the 3D VR condition from 2D screen and eyes opened no task conditions with an overall accuracy of 80.3%. The findings in this study have implications for using VR applications as a therapeutic intervention for neuropathic pain in people with spinal cord injury.

The impact of computerised physician order entry on prescribing in general paediatric units in Hong Kong.

OBJECTIVES: This study aimed to evaluate the effect of a closed-loop computerised physician order entry (CPOE) system on prescribing in a general paediatric unit in Hong Kong. We studied the effect of the CPOE system on medication prescribing error and the characteristics of these errors before and after the implementation of the system. METHODS: This was a single-site, prospective, observational study at a public hospital's general paediatric unit in Hong Kong, conducted during the pre- and post-implementation of the system from March to April 2019 and 2020, respectively. Collected data included the number of medication orders processed, the number of prescribing errors identified, and the characteristics of errors, such as the severity, children's age group, drug formulation, and drug class. KEY FINDINGS: The prescribing error rate was significantly reduced from 6.7% to 3.9% after CPOE implementation. The causes of prescribing errors were found to be significantly different, as the implementation eradicated handwriting-related errors and reduced dosage selection-related errors. However, we found that CPOE increased other causes of error, such as missing entry of patient information that might affect the dispensing process, thus delaying patients in receiving their medications on time. CONCLUSION: The CPOE system significantly reduced prescribing errors and altered some of the characteristics of these errors. Poor system design or inadequate user training could result in the creation of new causes of error.

Co-occurring Hearing Loss and Cognitive Decline in Older Adults: A Dual Group-Based Trajectory Modeling Approach.

Hearing loss and cognitive impairments are both highly prevalent neurological complications for older adults. While there is growing evidence to suggest that these two conditions are interrelated, little research has been conducted that directly examines the progression and developmental trajectories of these complications contemporaneously. The aim of the study is to identify the distinct trajectory profiles for hearing loss and cognitive function in an older population over a 10-year period. Through dual trajectory modeling, the interrelationship, co-occurring movements, and overlaps between these two complications were examined. We also investigated the influence of hearing aid ownership on cognitive function trajectories. We utilized longitudinal data from 1,445 participants in the Blue Mountains Hearing Study (aged 55+ years) involving repeated measures from a population-based survey with audiometric hearing assessments. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). The group-based trajectory modeling (GBTM) identified three trajectory profiles for both hearing loss and cognitive function in two older age groups (55-69 years and 70+ years). The outputs from the dual trajectories models showed the conditional probability for "no hearing loss" trajectories to be around 90% more likely to have "high-normal" cognitive function, demonstrating co-occurring overlap. In contrast, for "moderate to severe hearing loss" trajectories, the conditional probability drops to 65% and 79% for the 55-69 age group and 70+ age group respectively. There was also an increasing probability for "cognitive decline" conditional on the severity of hearing loss with 6.7%, 7.5%, and 8.7% for no hearing loss, mild hearing loss, and moderate to severe hearing loss trajectory groups. While we did not find any statistically significant difference in the influence of hearing aid use in the cognitive function trajectories, there was a consistent greater representation of non-hearing aid users in the trajectories with poorer cognitive function. This study found GBTM to identify trajectories that were in agreement with our current understanding of hearing loss and cognitive impairment in older adults. This study also adds to the existing evidence-base as dual trajectories demonstrated co-occurrence in developmental changes in these two common neurological complications for the older population.

Reexamining the Validity and Dimensionality of the Moorong Self-Efficacy Scale: Improving Its Clinical Utility.

OBJECTIVE: To improve the clinical utility of the Moorong Self-Efficacy Scale (MSES) by reexamining its factor structure and comparing its performance against a measure of general self-efficacy in persons with spinal cord injury (SCI). DESIGN: Cross-sectional survey design. SETTING: Community. PARTICIPANTS: Adults with SCI (N=161; 118 men and 43 women) recruited from Australia (n=82) and the United States (n=79), including 86 with paraplegia and 75 with tetraplegia. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Confirmatory factor analysis deriving fit indices on reported 1-, 2-, and 3-factor structures for the MSES. Exploratory factor analysis of MSES using principal component analysis with promax oblique rotation and structure validation, with correlations and multiple regression using cross-sectional data from the Sherer General Self-Efficacy Scale and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: The MSES was confirmed to have a 3-factor structure, explaining 61% of variance. Two of the factors, labeled social function self-efficacy and personal function self-efficacy, were SCI condition-specific, whereas the other factor (accounting for 9.7% of variance) represented general self-efficacy, correlating most strongly with the Sherer General Self-Efficacy Scale. Correlations and multiple regression analyses between MSES factors, Sherer General Self-Efficacy Scale total score, SF-36 Physical and Mental Component Summary scores, and SF-36 domain scores support validity of this MSES factor structure. No significant cross-cultural differences existed between Australia and the United States in total MSES or factor scores. CONCLUSIONS: The findings support a 3-factor structure encompassing general and SCI domain-specific self-efficacy beliefs and better position the MSES to assist SCI rehabilitation assessment, planning, and research.

Functional Priorities in Persons with Spinal Cord Injury: Using Discrete Choice Experiments To Determine Preferences.

Major goals of rehabilitation and health interventions in people with spinal cord injury (SCI) are to improve functional independence, increase social participation, and enhance quality of life (QOL). Determining functional areas perceived by consumers as most important can assist in research prioritization, planning for delivery of health services, and policy development. Five high priority areas of functioning for the SCI population (arm/hand use, walking, bladder/bowel control, sexual function, and relief of pain) were chosen to determine the preferences for these five attributes. A discrete choice experiment was conducted involving 151 persons with SCI sampled from Australia and the United States of America. Consistent with prior research, arm/hand function had the highest preference, with odds ratios of subjects being 44-76% more likely to choose arm/hand function over the other four functions. Preference for normal arm/hand function was found to be significantly more preferred by the group with paraplegia compared with those with tetraplegia; that is, retaining and not trading off existing arm/hand function for other improved functions. There were no significant differences found in preferences between bladder/bowel function and walking or elimination of pain, although walking was preferred in earlier (≤ 10) post-injury years and pain amelioration became more important with a longer duration (>10 years) post-injury. Sexual function had the lowest preference when traded against the other four functions. Understanding the functional preferences of persons with SCI will help to inform future research design, as well as enabling successful translation of research into practice and health policy, meeting the needs of people with SCI.

Ambient air pollution and lung disease in China: health effects, study design approaches and future research.

Ambient air pollution in China has worsened following dramatic increases in industrialization, automobile use and energy consumption. Particularly bothersome is the increase in the PM2.5 fraction of pollutants. This fraction has been associated with increasing rates of cardio-respiratory disease in China and elsewhere. Ambient pollutant levels have been described in many of China's cities and are comparable to previous levels in southern California. Lung cancer mortality in China has increased since the 1970s and has been higher in men and in urban areas, the exact explanation for which has not been determined. The estimation of individual risk for Chinese citizens living in areas of air pollution will require further research. Occupational cohort and case-control designs each have unique attributes that could make them helpful to use in this setting. Other important future research considerations include detailed exposure assessment and the possible use of biomarkers as a means to better understand and manage the threat posed by air pollution in China.

Increasing fine particulate air pollution in China and the potential use of exposure and biomarker data in disease prevention.

Increased industrialization and urbanization have led to marked increases in air pollutants in China over the last decade. Pollutant levels in the north and eastern regions are often four times higher than current daily levels in the United States. Recent reports indicate a higher incidence of lung cancer and mortality in men and urban dwellers, but the contribution of air pollution to these findings remains unknown. Future studies that define individual exposures, combined with biomarkers linked to disease, will be essential to the understanding of risk posed by air pollution in China.

Epidemiology and potential risk factors of drug-related problems in Hong Kong paediatric wards.

AIMS: A drug-related problem (DRP) is 'an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome'. The extent and characteristics of DRPs in children in Hong Kong are unknown. The aim of this study was to determine the epidemiology of and identify riskf actors for DRPs in hospitalized children in Hong Kong. METHODS: This was a prospective cohort study in children aged 0­18 years who were admitted to a medical ward, paediatric intensive care unit or neonatal intensive care unit of seven Hong Kong hospitals, during a 3 month period. Patients' charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse potential risk factors associated with the incidence of DRPs. RESULTS: Three hundred and twenty-nine children (median age, 2 years; interquartile range, 0 months to 9 years) were included. In total, 82 DRPs were experienced by 69 patients. The overall incidence of DRPs was 21.0% (95% confidence interval, 16.7­25.8%). The incidence was higher in neonatal and paediatric intensive care units than medical wards. Dosing problems were the most frequently reported DRPs (n = 35; 42.7%), followed by drug choice problems (n = 19; 23.2%) and adverse drug reactions (n = 11; 13.4%). Sixty-seven (81.7%) DRP cases were assessed as preventable, 42 (51.2%) as minor and 40 (48.8%) as moderate. The number of prescribed drugs and 'certain infectious and parasitic diseases' were potential risk factors for occurrence of DRPs. CONCLUSIONS: Drug-related problems were common in hospitalized children in this study in Hong Kong; the most frequent were dosing and drug choice problems, and the majority of them were preventable. Polypharmacy and 'certain infectious and parasitic diseases' were potential risk factors.

Antagonistic functions of Dishevelleds regulate Frizzled3 endocytosis via filopodia tips in Wnt-mediated growth cone guidance.

How growth cones detect small concentration differences of guidance cues for correct steering remains a long-standing puzzle. Commissural axons engage planar cell polarity (PCP) signaling components to turn anteriorly in a Wnt gradient after midline crossing. We found here that Frizzled3, a Wnt receptor, undergoes endocytosis via filopodia tips. Wnt5a increases Frizzled3 endocytosis, which correlates with filopodia elongation. We discovered an unexpected antagonism between Dishevelleds, which may function as a signal amplification mechanism in filopodia where PCP signaling is activated: Dishevelled2 blocks Dishevelled1-induced Frizzled3 hyperphosphorylation and membrane accumulation. A key component of apical-basal polarity (A-BP) signaling, aPKC, also inhibits Dishevelled1-induced Frizzled3 hyperphosphorylation. Celsr3, another PCP component, is required in commissural neurons for anterior turning. Frizzled3 hyperphosphorylation is increased in Celsr3 mutant mice, where PCP signaling is impaired, suggesting Frizzled3 hyperphosphorylation does correlate with loss of PCP signaling in vivo. Furthermore, we found that the small GTPase, Arf6, which is required for Frizzled3 endocytosis, is essential for Wnt-promoted outgrowth, highlighting the importance of Frizzled3 recycling in PCP signaling in growth cone guidance. In a Wnt5a gradient, more Frizzled3 endocytosis and activation of atypical protein kinase C was observed on the side of growth cones facing higher Wnt5a concentration, suggesting that spatially controlled Frizzled3 endocytosis is part of the key mechanism for growth cone steering.

GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood.

Lymphocytes egress from lymphoid organs in response to sphingosine-1-phosphate (S1P); minutes later they migrate from blood into tissue against the S1P gradient. The mechanisms facilitating cell movement against the gradient have not been defined. Here, we show that heterotrimeric guanine nucleotide-binding protein-coupled receptor kinase-2 (GRK2) functions in down-regulation of S1P receptor-1 (S1PR1) on blood-exposed lymphocytes. T and B cell movement from blood into lymph nodes is reduced in the absence of GRK2 but is restored in S1P-deficient mice. In the spleen, B cell movement between the blood-rich marginal zone and follicles is disrupted by GRK2 deficiency and by mutation of an S1PR1 desensitization motif. Moreover, delivery of systemic antigen into follicles is impaired. Thus, GRK2-dependent S1PR1 desensitization allows lymphocytes to escape circulatory fluids and migrate into lymphoid tissues.

Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance.

Although a growing body of evidence supports that Wnt-Frizzled signaling controls axon guidance from vertebrates to worms, whether and how this is mediated by planar cell polarity (PCP) signaling remain elusive. We show here that the core PCP components are required for Wnt5a-stimulated outgrowth and anterior-posterior guidance of commissural axons. Dishevelled1 can inhibit PCP signaling by increasing hyperphosphorylation of Frizzled3 and preventing its internalization. Vangl2 antagonizes that by reducing Frizzled3 phosphorylation and promotes its internalization. In commissural axon growth cones, Vangl2 is predominantly localized on the plasma membrane and is highly enriched on the tips of the filopodia as well as in patches of membrane where new filopodia emerge. Taken together, we propose that the antagonistic functions of Vangl2 and Dvl1 (over Frizzled3 hyperphosphorylation and endocytosis) allow sharpening of PCP signaling locally on the tips of the filopodia to sense directional cues, Wnts, eventually causing turning of growth cones.

Rab 11 regulates constitutive dopamine transporter trafficking and function in N2A neuroblastoma cells.

The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission which undergoes constitutive and substrate-mediated trafficking to and from the membrane. Although, considerable research has been done to elucidate the regulation of substrate-stimulated DAT trafficking, less is known about which trafficking proteins are involved in constitutive DAT trafficking. Rab proteins are GTPases known to regulate the trafficking of proteins to and from specific endocytic compartments. Rabs 8 and 11, in particular, are involved in trafficking proteins from intracellular compartments to the plasma membrane. In this study, we sought to determine whether Rabs 8 and 11 would modulate DAT activity and trafficking in N2A neuroblastoma cells. We used Rab mutations known to confer constitutively active or dominant negative activity of these proteins to investigate the role of Rab activity in constitutive DAT trafficking and function. We found that constitutively active Rab 11 upregulates DAT function and surface expression while neither the constitutively active nor the dominant negative mutant of Rab 8 had any effect on DA uptake. Furthermore, immunofluorescence experiments revealed that dominant negative Rab 11 overexpression results in decreased surface DAT indicating a necessary function of Rab 11 in DAT trafficking to the plasma membrane. These data show for the first time a functional role of Rab proteins in the constitutive recycling of DAT to the plasma membrane.

Image-guided robotic neurosurgery--an in vitro and in vivo point accuracy evaluation experimental study.

BACKGROUND: We describe the development of a prototype neurosurgical robotic system called NISS. The aim is to implement a robotic system capable of achieving accurate registration of robotic coordinate systems based on CT images, so that it can be used in clinical application. This system has been refined with a better level of predictability, reliability, and robustness sufficient for animal trial evaluation in stereotactic biopsy of brain lesions. METHODS: Point accuracy evaluation of NISS began with an in vitro study. The in vitro robotic application accuracy result was 0.1 +/- 0.05 mm and absolute needle-to-target deviation was 0.3 +/- 0.2 mm. An in vivo experiment approach of using steel balls of 1.56-mm-diameter as targets inside the brain of an anaesthetized dog was used to evaluate the performance accuracy of NISS stereotactic probe placement. Five dogs underwent surgical insertion of steel balls into the brain, and the steel balls were served as targets to be reached by a core needle (1.56-mm-diameter). The experiment was carried out by precise manipulation of the needle to reach the steel ball using frameless stereotactic localization principles. RESULTS: A total of 9 needle results were collected from procedures involving 5 dogs. In the first 5 procedures on 3 dogs, the results were less than 1.9 mm, with an average of 1.3 +/- 0.5 mm. The remaining 4 procedures on 2 dogs yielded results of less than 0.7 mm, with an average of 0.3 +/- 0.2 mm. CONCLUSION: The in vitro and in vivo studies represent the first approach toward evaluating targeting accuracy of a robotic surgery system by using stereotactics biopsy application in a living subject.

Phosphatidylinositol-3-kinase-atypical protein kinase C signaling is required for Wnt attraction and anterior-posterior axon guidance.

Wnt proteins are conserved axon guidance cues that control growth cone navigation. However, the intracellular signaling mechanisms that mediate growth cone turning in response to Wnts are unknown. We previously showed that Wnt-Frizzled signaling directs spinal cord commissural axons to turn anteriorly after midline crossing through an attractive mechanism. Here we show that atypical protein kinase C (aPKC), is required for Wnt-mediated attraction of commissural axons and proper anterior-posterior (A-P) pathfinding. A PKCzeta pseudosubstrate, a specific blocker of aPKC activity, and expression of a kinase-defective PKCzeta mutant in commissural neurons resulted in A-P randomization in "open-book" explants. Upstream of PKCzeta, heterotrimeric G-proteins and phosphatidylinositol-3-kinases (PI3Ks), are also required for A-P guidance, because pertussis toxin, wortmannin, and expression of a p110gamma kinase-defective construct all resulted in A-P randomization. Overexpression of p110gamma, the catalytic subunit of PI3Kgamma, caused precocious anterior turning of commissural axons before midline crossing in open-book explants and caused dissociated precrossing commissural axons, which are normally insensitive to Wnt attraction, to turn toward Wnt4-expressing cells. Therefore, we propose that atypical PKC signaling is required for Wnt-mediated A-P axon guidance and that PI3K can act as a switch to activate Wnt responsiveness during midline crossing.

S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress.

The mechanism by which sphingosine-1-phosphate receptor-1 (S1P1) acts to promote lymphocyte egress from lymphoid organs is not defined. Here, we showed that CCR7-deficient T cells left lymph nodes more rapidly than wild-type cells did, whereas CCR7-overexpressing cells were retained for longer. After treatment with FTY720, an agonist that causes downmodulation of lymphocyte S1P1, CCR7-deficient T cells were less effectively retained than wild-type T cells. Moreover, treatment with pertussis toxin to inactivate signaling via G alpha i-protein-coupled receptors restored egress competence to S1P1-deficient lymphocytes. We also found that T cell accumulation in lymph node cortical sinusoids required intrinsic S1P1 expression and was antagonized by CCR7. These findings suggest a model where S1P1 acts in the lymphocyte to promote lymph node egress by overcoming retention signals mediated by CCR7 and additional G alpha i-coupled receptors. Furthermore, by simultaneously upregulating S1P1 and downregulating CCR7, T cells that have divided multiple times switch to a state favoring egress over retention.