The Median Effective Dose of Dexmedetomidine for the Inhibition of Emergence Delirium in Preschool Children Undergoing Tonsillectomy and/or Adenoidectomy: A Retrospective Dose-response Trial.

The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 µg·kg-1·h-1. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 µg·kg-1·h-1 (95% CI: .29-.35) and .48 µg·kg-1·h-1 (95% CI: .44-.56), respectively. Probit(p) = -2.84 + 9.28 × ln (Dose), (χ2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.

4,8-Dicarboxyl-8,9-iridoid-1-glycoside inhibits apoptosis in human osteoarthritis chondrocytes via enhanced c-MYC-mediated cholesterol metabolism in vitro.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease related to cholesterol metabolism disorders. However, current therapies for OA are insufficient and no convincing disease-modifying OA drugs exist. Therefore, we aimed to elucidate the mechanism by which borojoa iridoid glycoside (BIG) inhibits chondrocyte apoptosis in OA. METHODS: Borojoa pulp was heated to 70 °C, and the main active substance in borojoa, BIG, was extracted by fractionation at an ultraviolet 254-nm absorption peak. Chondrocytes were identified by immunohistochemistry and visualized by immunofluorescence confocal microscopy. The proliferation of chondrocytes cultured with BIG was determined by MTS assay. The apoptosis of chondrocytes cultured with BIG was tested by Annexin V-FITC/PI, and the cytokine, protein, and cholesterol levels in chondrocytes were detected by ELISA, RT‒qPCR, Western blot, and biochemistry analyses. Protein‒protein interactions were verified by a coimmunoprecipitation (Co-IP) assay. RESULTS: BIG promoted chondrocyte proliferation and reduced apoptosis in vitro. BIG induced an alteration of the total RNA profiles in chondrocytes, and bioinformatic analysis showed that BIG inhibited chondrocyte apoptosis by promoting c-MYC expression; KEGG analysis confirmed that BIG-inhibited apoptosis was enriched in the cell cycle pathway. Flow cell cycle experiments confirmed that BIG promoted chondrocyte proliferation by significantly increasing the S phase cell number. The c-MYC inhibitor 10058-F4 stimulated the increased expression of IL-1ß, IL-6, TNF-α, and AGEs and suppressed the cholesterol metabolism, which promoted chondrocyte apoptosis and autophagy. Co-IP analysis showed that BIG promoted the interaction of c-MYC and CH25H, Bcl-2, which suggests that BIG could inhibit chondrocyte apoptosis in part by enhancing c-MYC-mediated cholesterol metabolism. CONCLUSIONS: This study confirmed that BIG promotes chondrocyte proliferation and inhibits apoptosis and autophagy, and BIG improving OA is associated with cholesterol metabolism. The results identify a potential mechanism by which BIG enhances c-MYC-mediated CH25H regulation of cholesterol metabolism in vitro and suggest that BIG might be a promising new drug against OA.

Thyrotroph embryonic factor polymorphism predicts faster progression of Parkinson's disease in a longitudinal study.

The thyrotroph embryonic factor gene is a circadian clock-controlled gene. The rs738499 polymorphism of this gene has been suggested to be associated with depression and sleep disturbance in Parkinson's disease in previous cross-sectional studies. We aimed to investigate whether this single nucleotide polymorphism is associated with the progression rates of various motor and non-motor symptoms in patients with Parkinson's disease. We recruited 186 patients with Parkinson's disease for a longitudinal study. Motor and non-motor symptoms were assessed at baseline and follow-up, and 170 Parkinson's disease patients completed the clinical evaluation twice with an average follow-up period of 3.3 ± 1.1 years. A stepwise linear regression model was used to validate factors associated with Parkinson's disease symptoms' annual progression rates. Faster annual worsening rates of sleep quality and Hoehn-Yahr stage were found in carriers with the homozygous dominant (TT). After adjustment for related clinical factors, the rs738499 polymorphism showed a contribution of 3.1% to the annual decline rate on the Parkinson's Disease Sleep Scale score and a contribution of 5.5% to the annual increase rate of the Hoehn-Yahr stage. Additionally, anxiety and axial symptoms predicted the progression of sleep disturbances and motor staging. The TT genotype of rs738499 might be a potential predictor of rapid deterioration in sleep quality and Hoehn-Yahr stage in patients with Parkinson's disease and may advance the understanding of the genetic contributions to Parkinson's disease.

Identification of microRNAs for the early diagnosis of Parkinson's disease and multiple system atrophy.

MicroRNAs are reportedly involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease and multiple system atrophy. We previously identified 7 differentially expressed microRNAs in Parkinson's disease patients and control sera (miR-30c, miR-31, miR-141, miR-146b-5p, miR-181c, miR-214, and miR-193a-3p). To investigate the expression levels of the 7 serum microRNAs in Parkinson's disease and multiple system atrophy, 23 early Parkinson's disease patients (who did not take any anti- Parkinson's disease drugs), 23 multiple system atrophy patients, and 24 normal controls were recruited at outpatient visits in this study. The expression levels of the 7 microRNAs in serum were detected using quantitative real-time polymerase chain reaction. A receiver operating characteristic curve was used to evaluate whether microRNAs can differentially diagnose Parkinson's disease and multiple system atrophy. Clinical scales were used to analyze the correlations between serum microRNAs and clinical features. The results indicated that miR-214 could distinguish Parkinson's disease from the controls, and another 3 microRNAs could differentiate multiple system atrophy from the controls (miR-141, miR-193a-3p, and miR-30c). The expression of miR-31, miR-141, miR-181c, miR-193a-3p, and miR-214 were lower in multiple system atrophy than in Parkinson's disease (all P < 0.05). Combinations of microRNAs accurately discriminated Parkinson's disease from multiple system atrophy (area under the receiver operating characteristic curve = 0.951). For the correlation analysis, negative correlations were discovered between the expression of miR-214 and the Hamilton Anxiety Scale and Parkinson's Disease Non-Motor Symptom scores (all P < 0.05). Our results demonstrate that the distinctive characteristics of microRNAs differentiate Parkinson's disease and multiple system atrophy patients from healthy controls and may be used for the early diagnosis of Parkinson's disease and multiple system atrophy.

Validation of Revised Chinese Version of PD-CRS in Parkinson's Disease Patients.

There is a high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson's disease (PD) patients, but a Chinese version of cognitive rating scale that is specific and sensitive to PD patients is still lacking. The aims of this study are to test the reliability and validity of a Chinese version of Parkinson's disease-cognitive rating scale (PD-CRS), establish cutoff scores for diagnosis of Parkinson's disease dementia (PDD) and PD with mild cognitive impairment (PD-MCI), explore cognitive profiles of PD-MCI and PDD, and find cognitive deficits suggesting a transition from PD-MCI to PDD. PD-CRS was revised based on the culture background of Chinese people. Ninety-two PD patients were recruited in three PD centers and were classified into PD with normal cognitive function (PD-NC), PD-MCI, and PDD subgroups according to the cognitive rating scale (CDR). Those PD patients underwent PD-CRS blind assessment by a separate neurologist. The PD-CRS showed a high internal consistency (Cronbach's Alpha = 0.840). Intraclass Correlation coefficient (ICC) of test-retest reliability reached 0.906 (95% CI 0.860-0.935, p < 0.001). ICC of inter-rater reliability was 0.899 (95% CI 0.848-0.933, p < 0.001). PD-CRS had fair concurrent validity with MDRS (ICC = 0.731, 95% CI 0.602-0.816). All the frontal-subcortical items showed significant decrease in PD-MCI compared with the PD-NC group (p ≤ 0.001), but the instrument cortical items did not (confrontation naming p=0.717, copying a clock p=0.620). All the frontal-subcortical and instrumental-cortical functions showed significant decline in PDD compared with the PD-NC group (p ≤ 0.001). The cutoff value for diagnosis of PD-MCI is 80.5 with the sensitivity of 75.7% and the specificity of 75.0%, and for diagnosis of PDD is 73.5 with the sensitivity of 89.2% and the specificity of 98.9%. Revised Chinese version of PD-CRS is a reliable, acceptable, valid, and useful neuropsychological battery for assessing cognition in PD patients.

Comparison of Three Motor Subtype Classifications in de novo Parkinson's Disease Patients.

Objective: The aims of this study were to compare the characteristics of three motor subtype classifications in patients with de novo Parkinson's disease (PD) and to find the most suitable motor subtype classification for identifying non-motor symptoms (NMSs). Methods: According to previous studies, a total of 256 patients with de novo PD were classified using the tremor-dominant/mixed/akinetic-rigid (TD/mixed/AR), TD/indeterminate/postural instability and gait disturbance (PIGD), and predominantly TD/predominantly PIGD (p-TD/p-PIGD) classification systems. Results: Among the TD/mixed/AR subgroups, the patients with the AR subtype obtained more severe motor scores than the patients with the TD subtype. Among the TD/indeterminate/PIGD subgroups and between the p-TD and p-PIGD subgroups, the patients with the PIGD/p-PIGD subtype obtained more severe scores related to activities of daily living (ADL), motor and non-motor symptoms, including depression, anxiety, and sleep impairment, than the patients with the TD/p-TD subtype. Furthermore, symptoms in the cardiovascular, gastrointestinal, and miscellaneous domains of the Non-motor Questionnaire (NMSQuest) were more prevalent in the patients with the PIGD/p-PIGD subtypes than the patients with the TD/p-TD subtypes. Conclusions: The PIGD/p-PIGD subtypes had more severe ADL, motor and non-motor symptoms than the TD/p-TD subtypes. We disclosed for the first time that the TD/indeterminate/PIGD classification seems to be the most suitable classification among the three motor subtype classifications for identifying NMSs in PD.

Cognitive impairment in patients with Parkinson's disease: A 30-month follow-up study.

OBJECTIVE: A longitudinal (30-month) study of the cognitive changes in Parkinson's disease patients and analysis of influencing factors. METHODS: The cognitive function and related symptoms of 102 patients with idiopathic Parkinson's disease were assessed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and relevant scales, at baseline and 30-month follow-up. The t-test, nonparametric tests, and regression analyses were used to evaluate cognitive decline and investigate risk factors for cognitive impairment. RESULTS: From baseline to follow-up, the MMSE and MoCA scores significantly decreased, respectively, from 28.16±2.29 to 26.18±3.64, and from 24.60±4.23 to 21.94±5.47 (both P<0.001). Impairment was observed in multiple cognitive areas, significantly in naming, delayed recall, and orientation (P<0.01). Patients at baseline with postural instability and gait disturbance (PIGD), lower MoCA scores, or depression had a higher risk of cognitive impairment at follow-up (P<0.01). CONCLUSION: Cognitive impairment is highly prevalent in Parkinson's disease patients, especially for those with lower MoCA scores, PIGD, and depression.

A panel of four decreased serum microRNAs as a novel biomarker for early Parkinson's disease.

CONTEXT: Sensitive, non-invasive biomarkers that facilitate Parkinson's disease (PD) detection and stage assignment are currently unavailable. OBJECTIVE: The objective of this study is to investigate the potential of circulating microRNAs (miRNAs) as novel biomarkers for PD. MATERIALS AND METHODS: Solexa sequencing technology and quantitative real-time PCR were applied to screen and verify altered serum miRNAs in PD patients. RESULTS: Serum miR-141, miR-214, miR-146b-5p, and miR-193a-3p were decreased significantly in PD patients compared with controls. Furthermore, the 4-miRNA panel enabled the differentiation of HY stage 1 and 2 PD patients from controls. DISCUSSION AND CONCLUSION: The four serum miRNAs may represent novel biomarkers for the early detection of PD.

The Natural History of Depression in Parkinson's Disease within 30-Month Follow-Up.

Depression is one of the most common and persistent nonmotor syndromes occurring in 35% of patients diagnosed with PD. However, little information is known about the longitudinal study of its natural history of depression in PD. In this study, we identified 110 patients who are diagnosed with idiopathic PD and recruited them for assessing information about their PD related motor and nonmotor symptoms and rating scales. A follow-up evaluation was performed in 103 patients 30 months later. About 66.7% depressed patients at baseline were still depressed at follow-up, and 24.4% had incident depression among subjects without depression at baseline. Greater decline on MMSE (P = 0.029), higher baseline UPDRS-II (P < 0.001) score, change of UPDRS-II (P = 0.026), and female (P < 0.001) were associated with the worsening of HDRS scores. Higher baseline HDRS score (P < 0.001) and greater decline on MMSE (P = 0.001) were related to the occurrence of depression. In conclusion, cognitive decline is a disease related factor of worsening and the occurrence of depression. Activities of Daily Living (ADL) symptoms in PD and female gender may be crucial factors of increasing depressive symptoms.

Using the Montreal Cognitive Assessment Scale to screen for dementia in Chinese patients with Parkinson's Disease.

BACKGROUND: Dementia is one of the most distressing and burdensome health problems associated with Parkinson's Disease (PD). The Montreal Cognitive Assessment scale (MoCA) is widely used to screen for dementia in PD patients, but the appropriate diagnostic cutoff score when used with Chinese PD patients is not known. AIM: Determine a diagnostic cutoff value of the Chinese version of the MoCA (MoCA-C) for Chinese PD patients and describe the characteristics of PD patients screened positive for dementia using the MoCA-C. METHODS: The presence of dementia in 616 PD patients and 85 community controls was determined using the Movement Disorder Society Task Force criteria (the gold standard diagnosis). We administered the MoCA-C to these individuals and used a receiver operating characteristic (ROC) curve to identify the cutoff score of the MoCA-C that most efficiently identified dementia in both PD patients and community controls. Demographic and clinical characteristics of PD patients who were screened positive or negative for dementia using the MoCA-C were compared. RESULTS: A MoCA-C score of 23 was the optimal cutoff score for dementia in both patients and controls. Using this cutoff score, the sensitivity and specificity of the MoCA-C in PD patients were 0.70 and 0.77, respectively; the positive and negative predictive values were 0.59 and 0.85, respectively; and the overall concordance (kappa [95% confidence interval]) was 0.45 (0.39-0.52). The corresponding kappa value (concordance) in community controls was only 0.25 (0.05-0.45). Compared to PD patients who screened negative for dementia, those who screened positive for dementia were significantly impaired in all cognitive domains, including visuospatial and executive functioning, naming, attention, language, abstraction, delayed recall and orientation (all p<0.001). Among the PD patients, screening positive for dementia was independently associated with old age, low educational attainment, female gender and more severe motor impairment. CONCLUSIONS: The commonly recommended cutoff screening score for dementia of 26 on the MoCA it too high for PD patients in China; a cutoff score of 23 is more appropriate. Potential risk factors for dementia in Chinese PD patients include older age, less education, and more severe motor symptoms of PD.