A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Dihydroisotanshinone I and BMAL-SIRT1 Pathway in an In Vitro 6-OHDA-Induced Model of Parkinson's Disease.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

Association between sleep health and intrinsic capacity among older adults in Taiwan.

Although the association between poor sleep quality and frailty has been previously reported, the relationship between sleep health and intrinsic capacity (IC) remains largely unknown. We aimed to examine the association between sleep health and IC among older adults. This was a cross-sectional study, and 1268 eligible participants completed a questionnaire collecting information on demographic, socioeconomic, lifestyle, sleep health, and IC. Sleep health was measured by the RU-SATED V2.0 scale. High, moderate, and low levels of IC were defined using the Integrated Care for Older People Screening Tool for Taiwanese. The ordinal logistic regression model estimated the odds ratio and corresponding 95% confidence interval. Low IC was significantly associated with age of 80 years or above, female, currently unmarried, uneducated, currently not working, financially dependent, and having emotional disorders. A one-point increase in sleep health was significantly associated with a 9% reduction in the odds of poor IC. An increase in daytime alertness was related to the greatest reduction in poor IC (aOR, 0.64; 95% CI, 0.52-0.79). In addition, the subitems sleep regularity (aOR, 0.77; 95% CI, 0.60-0.99), sleep timing (aOR, 0.80; 95% CI, 0.65-0.99), and sleep duration (aOR, 0.77; 95% CI, 0.61-0.96) were associated with a reduced OR of poor IC but with marginal statistical significance. Our findings showed that sleep health across multiple dimensions is related to IC, particularly daytime alertness in older adults. We suggest developing interventions to improve sleep health and prevent IC decline, which is crucial in causing poor health outcomes.

The Association between Ankle-Brachial Index/Pulse Wave Velocity and Cerebral Large and Small Vessel Diseases in Stroke Patients.

(1) Background: The study investigated whether the ankle-brachial index (ABI) and pulse wave velocity (baPWV) could reflect the severity of small vessel disease (SVD) and large artery atherosclerosis (LAA). (2) Methods: A total of 956 consecutive patients diagnosed with ischemic stroke were prospectively enrolled from July 2016 to December 2017. SVD severity and LAA stenosis grades were evaluated via magnetic resonance imaging and carotid duplex ultrasonography. Correlation coefficients were calculated between the ABI/baPWV and measurement values. Multinomial logistic regression analysis was performed to determine predictive potential. (3) Results: Among the 820 patients included in the final analysis, the stenosis grade of extracranial and intracranial vessels was inversely correlated with the ABI (p < 0.001, respectively) and positively correlated with the baPWV (p < 0.001 and p = 0.004, respectively). Abnormal ABI, not baPWV, independently predicted the presence of moderate (adjusted odds ratio, aOR: 2.18, 95% CI: 1.31-3.63) to severe (aOR: 5.59, 95% CI: 2.21-14.13) extracranial vessel stenosis and intracranial vessel stenosis (aOR: 1.89, 95% CI: 1.15-3.11). Neither the ABI nor baPWV was independently associated with SVD severity. (4) Conclusions: ABI is better than baPWV in screening for and identifying the existence of cerebral large vessel disease, but neither test is a good predictor of cerebral SVD severity.

6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma.

Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.

Fear of falling as a potential complication of Ramsay Hunt syndrome in older adults: a case report.

BACKGROUND: Fear of falling (FOF) is a common and major health concern in older adults. The consequences of FOF include reduced physical performance, social activity, and health-related quality of life. Ramsay Hunt syndrome (RHS) is a herpes zoster-related facial nerve dysfunction accompanied by an erythematous vesicular rash on the ear or mouth that may complicate ipsilateral facial paralysis and otalgia, vertigo, tinnitus, hearing loss, and meningoencephalitis. However, repeated falls and subsequent FOF due to RHS have not been reported in older adults. CASE PRESENTATION: A 65-year-old woman diagnosed with RHS experienced repeated falls during hospital admission and after discharge. Despite recovery of balance and no subsequent falls, the patient presented with persistent FOF at the geriatric outpatient follow-up visit 1 year after the RHS episode. The fear sensation impaired the patient's instrumental daily activities and was confirmed by documentation of serial comprehensive geriatric assessments, especially the Timed Up and Go test scores. CONCLUSIONS: RHS may cause repeated falls and FOF, leading to impairment in daily activities and psychosocial function in older adults. Therefore, clinicians should be mindful of falls and FOF when caring for older patients with RHS and should develop multidimensional strategies for fall prevention and FOF.

Investigating the interaction between neuropsychiatry features and daily activities on social function in patients with Parkinson's disease with mild cognitive impairment.

BACKGROUND: Social functioning is crucial for daily living and is an essential indicator of dementia in patients with Parkinson's disease. The pattern of social functioning in patients with Parkinson's disease without dementia (i.e. those who are cognitively intact or have mild cognitive impairment (PD-MCI)) and its determinants are unclear. AIMS: In exploring the heterogeneity of social functioning among patients with Parkinson's disease-associated dementia, we determined the optimal cut-off score of the Parkinson's Disease Social Functioning Scale (PDSFS) for patients with PD-MCI, and the variables influencing patients' social functioning. METHOD: A total of 302 participants underwent the Mini-Mental State Examination (MMSE) and PDSFS; 120 patients with Parkinson's disease completed the measurements (MMSE, Activities of Daily Living Scale and Neuropsychiatric Inventory). Group comparisons, receiver operating characteristic curves, Spearman correlation and multiple and hierarchical regression analyses were conducted. RESULTS: The PD-MCI group scored the lowest on the PDSFS (F = 10.10, P < 0.001). The PDSFS cut-off score was 53 (area under the curve 0.700, sensitivity 0.800, specificity 0.534). The MMSE (ß = 0.293, P = 0.002), Activities of Daily Living Scale (ß = 0.189, P = 0.028) and Neuropsychiatric Inventory (ß = -0.216, P = 0.005) scores predicted the PDSFS score. Further, there was an interaction effect between the Activities of Daily Living Scale and Neuropsychiatric Inventory scores on the PDSFS score (ß = 0.305, P < 0.001). CONCLUSIONS: We determined a PDSFS cut-off score for detecting PD-MCI and found that patients with PD-MCI have social dysfunction. Future research should focus on the effects of neuropsychiatry symptoms and activities of daily living on social functioning, and tailor the intervention programme for patients with Parkinson's disease.

Recurrent thromboembolism, bleeding, and mortality in Asian patients with venous thromboembolism receiving different oral anticoagulants: A nationwide analysis.

Venous thromboembolism (VTE) is associated with a high risk of morbidity and mortality. However, data on the association between oral anticoagulants and the hazards of VTE complications in Taiwanese patients with VTE is limited. This study aimed to compare the hazards of recurrent VTE, bleeding, and mortality between patients with VTE receiving rivaroxaban, a non-vitamin K antagonist oral anticoagulant (NOAC), and those receiving heparin or low-molecular-weight heparin (LMWH) followed by warfarin. Patients with VTE treated with rivaroxaban, or heparin or LMWH followed by warfarin were enrolled from 2 million random samples from Taiwan's National Health Insurance database between 2013 and 2016. Hazards of recurrent VTE (deep vein thrombosis and pulmonary embolism), major bleeding, and mortality in rivaroxaban and warfarin users were investigated. Survival analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Users of rivaroxaban (183) and warfarin (456) were included in the study. Patients receiving rivaroxaban did not have significantly lower hazards of developing recurrent VTE (HR, 0.72 [CI, 0.37-1.37], P = .31) and mortality (HR, 0.86 [CI, 0.49-1.50], P = .59) than those receiving heparin or LMWH followed by warfarin. In addition, the hazard ratio of major bleeding was not significantly different between the 2 regimens (HR, 1.80 [CI, 0.39-8.29], P = .45). Rivaroxaban was not associated with lower risks of recurrent VTE and mortality and higher hazards of major bleeding than heparin or LMWH followed by warfarin in Taiwanese patients with VTE. Clinicians may tailor oral anticoagulants for VTE patients according to the patient's characteristics, cost-effectiveness and healthcare system policy.

Cross-Sectional Analysis of Taiwanese Pharmacy Students' Experiences and Perceptions of Transitioning from In-Hospital Internships to Distance Learning Due to COVID-19.

The introductory pharmacy practice experiences (IPPE) in Taiwan, which are traditionally conducted in physical hospital settings, incorporated up to 30% distance learning from May 2021 due to Coronavirus Disease 2019 (COVID-19). A web-based cross-sectional survey was adopted to investigate pharmacy students' experiences and perceptions of transitioning from in-hospital internships to distance learning due to COVID-19 in the pharmacy department of a university in Southern Taiwan. We analyzed the results to discover factors that significantly affected students' perceptions of transitioning from in-hospital internships to distance learning. In total, 81 interns from the university's pharmacy department responded to the questionnaire. Approximately half of the participants felt happy when they learned, before the internship began, that the internship would be partially replaced with distance learning. The overall satisfaction rate was 67.9%, and no significant differences was observed in students' satisfaction between hospital size or distance-learning time. However, more students in the medical center felt they had insufficient time to finish assignments compared to those in the regional hospitals, and the students who had 11-15 days of distance learning felt that they interacted more smoothly with their peers compared to those who had other durations. Program designers should make distance internship courses more student-centered, with a focus on increasing interactions between students, teachers, and peers to compensate for the lack of physical presence.

A New Instrument Combines Cognitive and Social Functioning Items for Detecting Mild Cognitive Impairment and Dementia in Parkinson's Disease.

Background: The commonly used screening tests for Parkinson's disease (PD) are the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), both of which only focus on cognitive function. A composite assessment that considers both cognitive and social dysfunction in PD would be helpful in detecting mild cognitive impairment (MCI) and PD dementia (PDD). Objective: We aimed to simplify the commonly used tools and combine cognitive and social functioning tests to detect early MCI and PDD. Materials and Methods: A total of 166 participants (84 PD patients and 82 healthy) were recruited who completed the MMSE, MoCA, PD social functioning scale (PDSFS), clock drawing test, activities of daily living, comprehensive neuropsychological assessment (e.g., executive, attention, language, memory, and visuospatial functions), and movement disorder society (MDS)-unified PD rating scale. According to the MDS diagnostic criteria, the patients were grouped into PD-nonMCI, PD-MCI, or PDD. Results: To detect PD-MCI, the optimal cut-off scores for the simplified MoCA and the combined test were 9 and 35. The discrimination values measured by the area under the receiver operating characteristic curve (AUC) of the two tests were 0.767 (p < 0.001) and 0.790 (p < 0.001). When the simplified MoCA was 7 or the combined test 30, the patients would be classified as having PDD. The AUCs of the two tests were 0.846 (p < 0.001) and 0.794 (p = 0.003). Conclusion: We suggest considering both cognitive and social functions when detecting PD-MCI and PDD.

Clinical and Cellular Evidence of Glycyrrhiza glabra and Platycodon grandiflorus for Vocal Fold Nodules Complementary Treatment.

Vocal fold nodules (VFNs) are the most frequent cause of hoarseness. The management comprised medical, surgical and physical therapy but the effectiveness is not always satisfactory. In this study, we try to figure out an alternative treatment from our clinical experience summary. We retrospectively reviewed VFNs patients who received traditional Chinese medicine (TCM) treatments from July 2018 to August 2020 and traced their Chinese Voice Handicap Index-10 (VHI-C10) and multidimensional voice program (MDVP) analysis results. For further evaluation, we conducted an inflammatory response of porcine vocal fold epithelial (PVFE) cells with 50 ng/mL TNF-alpha. The inflamed PVFE cells were separately cultured in the aqueous extract of Glycyrrhiza glabra (G. glabra) and Platycodon grandifloras (P. grandifloras). In these VFNs patients (n = 22), the average VHI-C10 score decreased from 17.6 to 6.6 (p < 0.001). MDVP analysis revealed improvements in jitter, shimmer, noise-harmonic ratio, and GRBAS scoring system. Of the TCM prescription patterns, G. glabra and P. grandiflorus were used most frequently. In the MTT assay of PVFE cells, no adverse effects of our extracts were observed at doses of 1-200 µg/mL. Western blot analysis revealed downregulation of p65 and mitogen activated protein kinase pathway proteins. The results from both the clinical and in vitro aspects of this study revealed that the herbs G. glabra and P. grandiflorus may offer beneficial outcomes as alternative treatments for VFNs after precise diagnosis.

Ankle-Brachial Index Predicts Long-Term Renal Outcomes in Acute Stroke Patients.

Renal dysfunction is common after stroke. We aimed to investigate the clinical predictability of the ankle−brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) on poststroke renal deterioration. A total of 956 consecutive participants with acute ischemic stroke between 1 July 2016, and 31 December 2017 were enrolled and a final of 637 patients were recruited for final analysis. By using the group-based trajectory model (GBTM), the patients' renal function trajectories were grouped into the low, intermediate, and high categories (LC, IC, and HC). Significant deterioration in the slope was noted in the IC (p < 0.001) and LC (p = 0.002) groups but was nonsignificant in the HC (p = 0.998) group. Abnormal ABI (ABI ≤ 0.9) was independently related to LC (adjusted odds ratio: 2.40; 95% CI, 1.16−4.95; p = 0.019) and was also independently associated with increased risks of a ≥30% decline in eGFR (adjusted hazard ratio [aHR], 2.28; 95% CI, 1.29−4.05; p = 0.005), a doubling of serum creatinine (aHR, 3.60; 95% CI, 1.93−8.34; p < 0.001) and ESRD (HR, 3.28; 95% CI, 1.23−8.74; p = 0.018). However, baPWV did not have a significant relationship with any of the renal outcomes. Patients with a lower ABI during acute stroke should receive regular renal function tests and should be closely monitored to improve poststroke renal care.

Detailed risks and characteristics of postepilepsy stroke in non-traumatic adult-onset epilepsy.

BACKGROUND: Patients with epilepsy have an increased risk of stroke. However, the detailed risk and characteristics of postepilepsy stroke have not been investigated. METHODS: This study utilized the National Health Insurance Research Database in Taiwan. We classified adult patients with newly diagnosed epilepsy from 2003 to 2016 as the epilepsy cohort. Patients in the nonepilepsy cohort were selected with propensity score matching at a case-control ratio of 1:5. The incidence, hazard ratio (HR), period-specific HR, recurrent HR in the Wei-Lin-Weissfeld model, stroke severity index, complications, and mortality of all stroke, ischemic stroke (IS) and hemorrhagic stroke events in the two cohorts were analyzed. RESULTS: We enrolled 23,810 patients in the epilepsy cohort and 119,050 persons in the nonepilepsy cohort. The period-specific HRs of all stroke, IS and hemorrhagic stroke peaked immediately after epilepsy diagnosis and trended downward [Adjusted HRs of all stroke: 4.88 (3.88-6.14), 4.47 (3.50-5.70), 3.17 (2.62-3.84), 2.81 (2.27-3.48), 2.81 (2.36-3.34) and 2.33 (2.07-2.62) in 0-0.5, 0.5-1, 1-2, 2-3, 3-5 and ≥5 years after epilepsy diagnosis, respectively]. The recurrent stroke HRs in the epilepsy cohort were >1 from the first [3.06 (2.71-3.34)] to the fourth events [6.33 (1.08-37.03)]. IS events in the epilepsy cohort were associated with a younger onset age, a higher IS severity index, a higher rate of urinary tract infection, a lower in-hospital mortality, while 90-day stroke mortality was similar between the 2 cohorts. CONCLUSION: Since the increased risk of stroke in epilepsy cohort peaked immediately after epilepsy diagnosis, early implementation of prevention strategies is considered.

Hypomimia May Influence the Facial Emotion Recognition Ability in Patients with Parkinson's Disease.

BACKGROUND: Hypomimia is a clinical feature of Parkinson's disease (PD). Based on the embodied simulation theory, the impairment of facial mimicry may worsen facial emotion recognition; however, the empirical results are inconclusive. OBJECTIVE: We aimed to explore the worsening of emotion recognition by hypomimia. We further explored the relationship between the hypomimia, emotion recognition, and social functioning. METHODS: A total of 114 participants were recruited. The patients with PD and normal controls (NCs) were matched for demographic characteristics. All the participants completed the Mini-Mental State Examination and the Chinese Multi-modalities Emotion Recognition Test. In addition to the above tests, the patients were assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and Parkinson's Disease Social Functioning Scale (PDSFS). RESULTS: Patients with PD with hypomimia had worse recognition of disgust than NCs (p = 0.018). The severity of hypomimia was predictive of the recognition of disgust (ß= -0.275, p = 0.028). Facial emotion recognition was predictive of the PDSFS score of PD patients (ß= 0.433, p = 0.001). We also found that recognizing disgust could mediate the relationship between hypomimia and the PDSFS score (ß= 0.264, p = 0.045). CONCLUSION: Patients with hypomimia had the worst disgust facial recognition. Hypomimia may affect the social function of PD patients, which is related to recognizing the expression of disgust. Emotion recognition training may improve the social function of patients with PD.

Comparative effectiveness of neuraminidase inhibitors in patients with influenza: A systematic review and network meta-analysis.

The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated "value preference of SUCRA." This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.

The difference in the intracellular Arg/Lys-rich and EHLVY motifs contributes to distinct subcellular distribution of HAI-1 versus HAI-2.

The integral membrane, Kunitz-type, serine protease inhibitors, HAI-1 and HAI-2, closely resemble one another structurally and with regard to their specificity and potency against proteases. Structural complementarity between the Kunitz domains and serine protease domains renders the membrane-associated serine proteases, matriptase and prostasin, the primary target proteases of the HAIs. The shared biochemical enzyme-inhibitor relationships are, however, at odds with their behavior at the cellular level, where HAI-1 appears to be the default inhibitor of these proteases and HAI-2 a cell-type-selective inhibitor, even though they are widely co-expressed. The limited motility of these proteins caused by their membrane anchorages may require their co-localization within a certain distance to allow the establishment of a cellular level functional relationship between the proteases and the inhibitors. The differences in their subcellular localization with HAI-1 both inside the cell and on the cell surface, compared to HAI-2 predominately in intracellular granules has, therefore, been implicated in the differential manner of their control of matriptase and prostasin proteolysis. The targeting signals present in the intracellular domains of the HAIs are systematically investigated herein. Studies involving domain swap and point mutation, in combination with immunocytochemistry and cell surface biotinylation/avidin depletion, reveal that the different subcellular localization between the HAIs can largely be attributed to differences in the intracellular Arg/Lys-rich and EHLVY motifs. These intrinsic differences in the targeting signal render the HAIs as two independent rather than redundant proteolysis regulators.

The Impact of Sex on the Neurocognitive Functions of Patients with Parkinson's Disease.

This study aimed to understand the impact of sex on the neurocognitive function of patients with Parkinson's disease (PD). Ninety-four participants with idiopathic PD and 167 age-matched healthy individuals as normal controls (NCs) were recruited and underwent comprehensive neuropsychological assessments. Sex differences were found in NCs, but not in patients with PD. Among male participants, patients with PD showed worse performance on the Digit Symbol Substitution (DSS) (p < 0.001) test and Symbol Search (SS) (p < 0.001) than NCs. Among female participants, patients with PD showed worse performance on the category score of the Modified Wisconsin Card Sorting Test (p < 0.001), SS (p < 0.001), and pentagon copying (p < 0.001) than NCs. After controlling for the effects of age and years of education, Hoehn and Yahr stage was found to predict the performance of the Color Trails Test part A (ßA = 0.241, pA = 0.036), Stroop Color and Word Test (ß = -0.245, p = 0.036), and DSS (ß = -0.258, p = 0.035) in men with PD. These results indicate the differential effect of sex on the neurocognitive function among healthy aging and PD populations. The disappearance of sex differences, which is present in healthy aging, in patients with PD suggests a gradual loss of the neuroprotective effect of estrogen after the initiation of the neurodegenerative process. This study also found mental flexibility and visuospatial function to be the susceptible cognitive domains in women with PD, while the disease severity could predict the working memory and processing speed in men with PD.

Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects.

BACKGROUND: Ceftriaxone is a ß-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. METHODS: Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn's Gram staining. These parameters above were measured at 72 h after TBI. RESULTS: Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. CONCLUSIONS: The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Factors Associated with Cognitive Outcomes After First-Ever Ischemic Stroke: The Impact of Small Vessel Disease Burden and Neurodegeneration.

BACKGROUND: Differences exist regarding post-stroke cognitive outcomes. OBJECTIVE: The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. METHODS: We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. RESULTS: A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p < 0.001, respectively), but tended to be worse in patients with higher SVD burden and HA. The GBTM model grouped patients into low, intermediate, and high performance (LP, IP, and HP) after stroke. A higher SVD burden, rather than HA and initial stroke severity and location, independently predicted a higher odds of poor post-stroke cognitive trajectory (being in the LP group) after stroke (adjusted odds ratio 2.74, 95%CI 1.09-6.86). CONCLUSION: In patients with first-ever mild stroke, cognitive improvement over time was evident. The detrimental impact of the SVD burden may outweigh the effect of HA or acute stroke insult on the post-stroke cognitive trajectory during the 1-year follow-up.

Real-world evidence and optimization of vocal dysfunction in end-stage renal disease patients with secondary hyperparathyroidism.

Patients with end-stage renal disease (ESRD) may demonstrate secondary hyperparathyroidism (SHPT), characterized by parathyroid hormone oversecretion in response to electrolyte imbalance (e.g., hypocalcemia and hyperphosphatemia). Moreover, this electrolyte imbalance may affect vocal cord muscle contraction and lead to voice change. Here, we explored the effects of SHPT on the voices of patients with ESRD. We used data of 147,026 patients with ESRD from the registry for catastrophic illness patients, a sub-database of Taiwan National Health Insurance Research Database. We divided these patients into 2 groups based on whether they had hyperparathyroidism (HPT) and compared vocal dysfunction (VD) incidence among them. We also prospectively included 60 ESRD patients with SHPT; 45 of them underwent parathyroidectomy. Preoperatively and postoperatively, voice analysis was used to investigate changes in vocal parameters. In the real-world database analysis, the presence of HPT significantly increased VD incidence in patients with ESRD (p = 0.003): Cox regression analysis results indicated that patients with ESRD had an approximately 1.6-fold increased VD risk (p = 0.003). In the clinical analysis, the "jitter" and "shimmer" factors improved significantly after operation, whereas the aerodynamic factors remained unchanged. In conclusion, SHPT was an independent risk factor for VD in patients with ESRD, mainly affecting their acoustic factors.