Accumulating evidence implies that both AKT1 and GABAA receptor (GABAAR) subunit genes are involved in schizophrenia pathogenesis. Activated Akt promotes GABAergic neuron differentiation and increases GABAAR expression on the plasma membrane. To elucidate the role of Akt1 in modulating GABAergic functions and schizophrenia-related cognitive deficits, a set of 6 in vitro and in vivo experiments was conducted. First, an Akt1/2 inhibitor was applied to evaluate its effect on GABAergic neuron-like cell formation from P19 cells. Inhibiting Akt resulted in a reduction in parvalbumin-positive neuron-like cells. In Akt1−/− and wild-type mice, seizures induced using pentylenetetrazol (a GABAAR antagonist) were measured, and GABAAR expression and GABAergic interneuron abundance in the brain were examined. Female Akt1−/− mice, but not male Akt1−/− mice, exhibited less pentylenetetrazol-induced convulsive activity than their corresponding wild-type controls. Reduced parvalbumin-positive interneuron abundance and GABAAR subunit expression, especially in the hippocampus, were also observed in female Akt1−/− mice compared to female wild-type mice. Neuromorphometric analyses revealed significantly reduced neurite complexity in hippocampal pyramidal neurons. Additionally, female Akt1−/− mice displayed increased hippocampal oscillation power and impaired spatial memory compared to female wild-type mice. Our findings suggest that Akt1 deficiency modulates GABAergic interneurons and GABAAR expression, contributing to hippocampus-dependent cognitive functional impairment.
Critical shoulder angle (CSA) is the angle between the superior and inferior bony margins of the glenoid and the most lateral border of the acromion. The acromial index (AI) is the distance from the glenoid plane to the acromial lateral border and is divided by the distance from the glenoid plane to the lateral aspect of the humeral head. Although both are used for predicting shoulder diseases, research on their accuracy in predicting supraspinatus tendinopathy in patients with shoulder pain is limited. Data were retrospectively collected from 308 patients with supraspinatus tendinopathy between January 2018 and December 2019. Simultaneously, we gathered the data of 300 patients with shoulder pain without supraspinatus tendinopathy, confirmed through ultrasound examination. Baseline demographic data, CSA, and AI were compared using the independent Student’s t test and Mann–Whitney U test. Categorical variables were analyzed using the chi-square test. A receiver operating characteristic curve (ROC) analysis was performed to investigate the accuracy of CSA and AI for predicting supraspinatus tendinopathy, and the optimal cut-off point was determined using the Youden index. No statistical differences were observed for age, sex, body mass index, evaluated side (dominant), diabetes mellitus, and hyperlipidemia between the groups. The supraspinatus tendinopathy group showed higher CSAs (p < 0.001) than did the non-supraspinatus tendinopathy group. For predicting supraspinatus tendinopathy, the area under the curve (AUC) of ROC curve of the CSA was 76.8%, revealing acceptable discrimination. The AUC of AI was 46.9%, revealing no discrimination. Moreover, when patients with shoulder pain had a CSA > 38.11°, the specificity and sensitivity of CSA in predicting supraspinatus tendinopathy were 71.0% and 71.8%, respectively. CSA could be considered an objective assessment tool to predict supraspinatus tendinopathy in patients with shoulder pain. AI revealed no discrimination in predicting supraspinatus tendinopathy in patients with shoulder pain.
The aim of this study was to explore the association between employment status and World Health Organization Disability Assessment Schedule, Second Edition (WHODAS 2.0) scores of working-age subjects with hearing impairment. The data of 18,573 working-age subjects (age ≥ 18 and <65 years) with disabling hearing impairment were obtained from the Taiwan Data Bank of Persons with Disability (TDPD) for the period from 11 July 2012 to 31 October 2018. Demographic data and WHODAS 2.0 scores for each domain were analyzed to identify their relationship with employment status. Unemployed subjects with disabling hearing impairment had higher WHODAS 2.0 scores in all domains compared with the employed subjects. Binary logistic regression revealed that older age, female sex, lower educational level, institutional residence, rural residence, lower family income, and moderate to severe impairment were more strongly associated with unemployment status. The data in this large population-based study offer comprehensive information on important factors associated with the employment status of people with disabling hearing impairment. Early identification of risks of unemployment of patients with hearing impairment can raise awareness for aggressive community and government campaigns regarding public health to improve the self-confidence, social participation, and related psycho-social wellbeing of people.
Osteoarthritis is one of the leading causes of disability. Total knee arthroplasty (TKA) is a surgical intervention for patients with severe osteoarthritis. Post TKA rehabilitation is crucial for improving patient’s quality of life. However, traditional rehabilitation has only focused on physical function; a systemic analysis of other dimensions such as social participation and environmental factors of post TKA rehabilitation is lacking. The aim of this study was to develop a core set from the International Classification of Functioning, Disability and Health (ICF) to create a comprehensive rehabilitation program for patients with osteoarthritis post TKA. Before the Delphi-based consensus process, a literature review process was performed for related ICF categories selection. We used a three-round Delphi-based consensus among 20 physical therapists with orthopedic rehabilitation expertise in a university-based hospital. A five-point Likert scale was used to rate the importance of each item. The consensus of ratings was analyzed using Spearman’s rho and semi-interquartile range indices. The ICF core set for post TKA rehabilitation was determined based on a high level of consensus and a mean score of ≥4.0 in the third Delphi-based consensus round. The ICF core set comprised 32 categories, with 13 regarding body function, four regarding body structures, nine regarding activities and participation, four regarding environmental factors, and two regarding personal factors. Our ICF core set for post TKA rehabilitation can provide information on effective rehabilitation strategies and goal setting for patients post TKA. However, further validation and feasibility assessments are warranted.
Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that mainly affects the axial bones, and dementia is characterized by a decline in cognitive function, leading to dependence in everyday activity. Although the association between dementia and ankylosing spondylitis has been investigated, the influence of axSpA medication on dementia risk is unclear. The aim of this study was to investigate the risk of dementia among axSpA patients and if the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) can reduce the risk of dementia. Patients with axSpA whose data were recorded during 2004–2008 and who were followed up until the end of 2010 were recruited. A control cohort was matched by age and sex. A Cox multivariate proportional hazards model was applied to analyze the risk factors for dementia. The hazard ratio (HR) and adjusted HR (aHR) were estimated between the study and control cohorts. The effects of csDMARDs and steroid use on the risk of different types of dementia were also analyzed. In total, 2341 and 11,705 patients constituted the axSpA and control cohort, respectively. The axSpA cohort had a greater risk of vascular dementia (aHR = 2.09 (1.36–3.20). The risk of dementia (aHR = 1.01 (0.55–1.85) did not significantly differ between patients with axSpA who received csDMARDs. In conclusion, patients with axSpA are at a risk of vascular dementia, which could be reduced by csDMARDs.
Physical functional limitations and sleep disturbances frequently co-occur in older adults, yet their joint mortality risks and the potential nonlinear dynamics of systemic inflammation remain unclear. This study investigated the joint associations of health behavior profiles (physical function and sleep) and the systemic immune-inflammation index (SII) with mortality, focusing on exploring nonlinear relationships. Data were obtained from 4548 individuals who participated in the National Health and Nutrition Examination Survey (2011–2014). Survey-weighted Cox proportional hazards models and restricted cubic splines with change-point diagnostics were used to characterize exposure-response relationships. Compared with healthy controls, participants with physical functional limitations exhibited >2-fold increases in the risks of all-cause mortality (hazard ratio: 2.44) and cardiovascular mortality (hazard ratio: 2.46). Concurrent sleep disturbances conferred minimal additional risk. The association of SII value with mortality was nonlinear. Risk remained stable at lower SII values but increased sharply beyond identified model-based turning points (SII ≈ 447–644 for all-cause mortality; SII ≈ 332–643 for cardiovascular mortality). Physical functional limitations are robustly associated with mortality, overshadowing the contribution of sleep disturbances. The identified model-based turning points reflect an inflection in mortality risk, suggesting a potential threshold effect in systemic inflammation. Specifically, the findings highlight a unique susceptibility of the cardiovascular system to low-level inflammation. Given the observational nature of this study, these turning points are exploratory and warrant external validation.