Tag: pubmed

J Parkinsons Dis. 2021 Dec 22. doi: 10.3233/JPD-212819. Online ahead of print.

ABSTRACT

BACKGROUND: Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson’s disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance.

OBJECTIVE: Investigate a potential effect of statins on PD progression.

METHODS: Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participated PD Biomarker Program (PDBP, 2012-2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the “on” drug state. R2 * values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions.

RESULTS: Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2 * (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= -7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2 * did not reach statistical significance (β= 2.5, p = 0.24).

CONCLUSION: This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.

PMID:34958045 | DOI:10.3233/JPD-212819

J Alzheimers Dis. 2021 Dec 18. doi: 10.3233/JAD-215152. Online ahead of print.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) is a progressive age-dependent disorder whose risk is affected by genetic factors. Better models for investigating early effects of risk factors such as apolipoprotein E (APOE) genotype are needed.

OBJECTIVE: To determine whether APOE genotype produces neuropathologies in an AD-susceptible neural system, we compared effects of human APOE ɛ3 (E3) and APOE ɛ4 (E4) alleles on the mouse olfactory epithelium.

METHODS: RNA-Seq using the STAR aligner and DESeq2, immunohistochemistry for activated caspase-3 and phosphorylated histone H3, glucose uptake after oral gavage of 2-[1,2-3H (N)]-deoxy-D-glucose, and Seahorse Mito Stress tests on dissociated olfactory mucosal cells.

RESULTS: E3 and E4 olfactory mucosae show 121 differentially abundant mRNAs at age 6 months. These do not indicate differences in cell type proportions, but effects on 17 odorant receptor mRNAs suggest small differences in tissue development. Ten oxidoreductases mRNAs important for cellular metabolism and mitochondria are less abundant in E4 olfactory mucosae but this does not translate into differences in cellular respiration. E4 olfactory mucosae show lower glucose uptake, characteristic of AD susceptibility and consistent with greater expression of the glucose-sensitive gene, Asns. Olfactory sensory neuron apoptosis is unaffected at age 6 months but is greater in E4 mice at 10 months.

CONCLUSION: Effects of human APOE alleles on mouse olfactory epithelium phenotype are apparent in early adulthood, and neuronal loss begins to increase by middle age (10 months). The olfactory epithelium is an appropriate model for the ability of human APOE alleles to modulate age-dependent effects associated with the progression of AD.

PMID:34958025 | DOI:10.3233/JAD-215152

J Alzheimers Dis. 2021 Dec 22. doi: 10.3233/JAD-215163. Online ahead of print.

ABSTRACT

BACKGROUND: Tauopathy is a primary neuropathological hallmark of Alzheimer’s disease with a strong relationship to cognitive impairment. In the brain, tau aggregation is associated with the regulation of tau kinases and the binding ability of tau to microtubules.

OBJECTIVE: To explore the potential for using specific polygenic risk scores (PRSs), combining the genetic influences involved in tau-protein kinases and the tau-protein binding pathway, as predictors of tau pathology and cognitive decline in non-demented individuals.

METHODS: We computed a pathway-specific PRS using summary statistics from previous large-scale genome-wide association studies of dementia. We examined whether PRS is related to tau uptake in positron emission tomography (PET), tau levels, and the rate of tau level changes in cerebrospinal fluid (CSF). We further assessed whether PRS is associated with memory impairment mediated by CSF tau levels.

RESULTS: A higher PRS was related to elevated CSF tau levels and tau-PET uptake at baseline, as well as greater rates of change in CSF tau levels. Moreover, PRS was associated with memory impairment, mediated by increased CSF tau levels. The association between PRS and tau pathology was significant when APOE was excluded, even among females. However, the effect of PRS on cognitive decline appeared to be driven by the inclusion of APOE.

CONCLUSION: The influence of genetic risk in a specific tau-related biological pathway may make an individual more susceptible to tau pathology, resulting in cognitive dysfunction in an early preclinical phase of the disease.

PMID:34958026 | DOI:10.3233/JAD-215163

Clin Hemorheol Microcirc. 2021 Dec 21. doi: 10.3233/CH-211286. Online ahead of print.

ABSTRACT

PURPOSE: To thoroughly evaluate preoperative risk factors for deep venous thrombosis (DVT) in patients with knee rheumatoid arthritis (RA) undergoing unilateral total knee arthroplasty (TKA).

METHODS: Clinical data of 106 patients with knee RA who underwent unilateral TKA from August 2014 to October 2020 were collected. All patients received ultrasonic examination of the veins of both lower extremities on the third day after TKA and were divided into DVT and non-DVT groups. The associations between age, gender, body mass index (BMI), history of diabetes/hypertension, common serum lipid levels, indicators related to coagulation function, blood viscosity, erythrocyte sedimentation rate (ESR) and postoperative DVT were statistically compared and analyzed.

RESULTS: ESR was significantly correlated with DVT risk after TKA (OR = 1.844, 95% CI = 1.022-2.981, P = 0.019). Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off point of ESR for predicting DVT was 42 mm/h with a sensitivity of 95.5% and specificity of 66.7% .

CONCLUSION: An increased preoperative ESR value is a risk factor for DVT in patients with knee RA following unilateral TKA. Pre-surgery control of ESR level and prevention of postoperative DVT in these patients are worthy of attention.

PMID:34958010 | DOI:10.3233/CH-211286

J Alzheimers Dis. 2021 Dec 22. doi: 10.3233/JAD-215091. Online ahead of print.

ABSTRACT

BACKGROUND: APOEɛ4 allele confers greatest genetic risk for Alzheimer’s disease (AD), yet mechanisms underlying this risk remain elusive. APOE is involved in lipid metabolism, and literature suggest relationships between high total cholesterol, APOE, and AD. Further investigation is needed to elucidate the potential role of total cholesterol in AD risk.

OBJECTIVE: To investigate the relationship between total cholesterol and APOE-related AD risk in the Alzheimer’s Disease Neuroimaging Initiative.

METHODS: Participants (N = 1,534) were classified as controls (cognitively normal; N = 404), early mild cognitive impairment (MCI; N = 294), late MCI (N = 539), or AD (N = 297). Total cholesterol levels were compared across APOE genotype and diagnosis. Mendelian randomization was performed to examine causality between total cholesterol and AD risk using APOE as a genetic instrument.

RESULTS: Total cholesterol was higher in APOE4+ compared to APOE3 and APOE2+ (ps < 0.04) carriers. Those with AD and late MCI (ps < 0.001) had higher total cholesterol than the control group. Comparing APOE4+ to APOE3 carriers, the predicted odds ratios per mg/dL greater total cholesterol were 1.11 for MCI (95% confidence interval, 1.04-7.32), 1.05 for early MCI (1.01-3.22), 1.13 for late MCI (1.05-11.70), 1.21 for AD (1.09-54.05), and 1.13 for composite dementia (MCI or AD; 1.06-11.59) (ps < 0.05, F-statistics>10).

CONCLUSION: Higher total cholesterol may be a significant contributor to AD risk, particularly in APOE4 carriers who, based on existing literature, tend to have impaired cholesterol metabolism. Our findings highlight a possible mechanism by which APOE confers AD risk and indicate potential for AD risk modification through maintenance of healthy total cholesterol levels.

PMID:34958023 | DOI:10.3233/JAD-215091

Technol Health Care. 2021 Dec 24. doi: 10.3233/THC-213537. Online ahead of print.

ABSTRACT

BACKGROUND: Tracheotomy is one of the first-aid measures for rescuing critically ill patients.

OBJECTIVE: This study was designed to observe the clinical effect of using an innovative tracheotomy fixation belt in critically ill patients and to explore the feasibility of using this fixation method.

METHODS: Eighty critically ill patients requiring a tracheotomy in Putuo District Central Hospital of Shanghai were enrolled in this study and divided into the observation group and control group (n= 40, each). In the control group, fixation was performed with conventional cotton twill tape, while in the observation group the fixation was carried out using a tracheotomy fixation belt. The differences in neck skin injury, the occurrence of eczema, and the rate of detachment of the tracheotomy tube in the two groups were compared.

RESULTS: The rate of neck skin injury was 7.5% lower in the observation group than in the control group (30%), and the difference was statistically significant (p< 0.05). The incidence of skin eczema was 5% lower in the observation group than in the control group (22.5%), and the difference was statistically significant (p< 0.05). The detachment rate of the tracheotomy tube was 5% lower in the observation group than in the control group (20%), and the difference was statistically significant (p< 0.05).

CONCLUSION: The use of an innovative tracheotomy fixation belt can effectively reduce skin damage to the patient’s neck, the incidence of eczema, and the incidence of detachment of the tracheotomy tube.

PMID:34957970 | DOI:10.3233/THC-213537

J Back Musculoskelet Rehabil. 2021 Dec 15. doi: 10.3233/BMR-210170. Online ahead of print.

ABSTRACT

BACKGROUND: Ultrasound is increasingly being utilized in the diagnosis and treatment of adhesive capsulitis.

OBJECTIVE: To compare the therapeutic effects and advantages of combined handheld ultrasound and fluoroscopy-guided intra-articular corticosteroid injection with those of conventional ultrasound-guided corticosteroid injection in adhesive capsulitis of the shoulder.

METHODS: A total of 39 patients diagnosed with adhesive capsulitis of the shoulder were randomly assigned into two groups. Group A patients (n= 19) underwent combined handheld ultrasound and fluoroscopy-guided corticosteroid injection and group B patients (n= 20) underwent conventional ultrasound-guided corticosteroid injection to the intra-articular space of the shoulder twice. Treatment efficacy was assessed at 2 and 6 weeks after the final injection, based on the verbal numeric pain scale, Shoulder Pain and Disability Index, and range of motion. Secondary outcome measures were the accuracy and procedure time.

RESULTS: Both injection methods were effective in the treatment of adhesive capsulitis. No significant differences in treatment efficacy and injection accuracy were observed between the two groups (p> 0.05).

CONCLUSIONS: This study showed no statistical differences in treatment efficacy between 2 groups. However, the combined use of ultrasound and fluoroscopy can increase the accuracy of injection compared with conventional ultrasound alone.

PMID:34957992 | DOI:10.3233/BMR-210170

Zhonghua Yi Xue Za Zhi. 2021 Dec 28;101(48):3961-3965. doi: 10.3760/cma.j.cn112137-20210630-01479.

ABSTRACT

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m². The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

PMID:34954999 | DOI:10.3760/cma.j.cn112137-20210630-01479

Zhonghua Yi Xue Za Zhi. 2021 Dec 28;101(48):3944-3949. doi: 10.3760/cma.j.cn112137-20210428-01023.

ABSTRACT

Objective: To investigate the role of ubiquitin-specific peptidase 22 (USP22) in colorectal cancer multidrug resistance and its correlation with multidrug resistance genes P-gp and MRP1, and to preliminarily explore the mechanism of USP22 affecting colorectal cancer resistance. Methods: USP22 over-expression plasmid was transfected into colorectal cancer cells (RKO, SW480)with low expression of USP22. Cell counting kit (CCK-8) assay was used to detect the effect of USP22 on oxaliplatin resistance in colorectal cancer cells. The cells were treated with oxaliplatin of the same concentration. Western blot method was used to detect the expression of apoptosis-related proteins cleaved-caspase3, Bcl-2, and drug resistance proteins MRP1, P-gp in the cells. The cell efflux test was used to detect the effect of up-regulated USP22 on Calcein-AM and rhodamine123. Immunohistochemical methods were used to detect the expressions of USP22 and P-gp in the oxaliplatin chemotherapy-sensitive group and the drug-resistant group and to analyze the correlation between USP22 and MRP1, P-gp. Results: CCK-8 assay showed that the IC₅₀ values of SW480-USP22 (SW480 cells overexpressing USP22) treated with oxaliplatin for 24 h and 48 h was (4.62±0.05)μmol/L and (2.32±0.04)μmol/L respectively; which was 2.7 times and 3.0 times higher than that in control cells, respectively. After treating with 1.25 μmol/L oxaliplatin for 48 h, USP22 overexpression can inhibit SW480 cells apoptosis. The fluorescence intensity of calcein-AM and rhodamine123 in the SW480-USP22 group were significantly increased when compared with that in the control cells (both P<0.01). The protein expression levels of MRP1 and P-gp in SW480-USP22 cells were significantly increased when compared with that in the control cells(both P<0.01). Immunohistochemistry showed that the positive expression rates of USP22, MRP1, and P-gp in the oxaliplatin chemotherapy-sensitive group were significantly lower than those in the chemotherapy-resistant group, the difference was statistically significant (all P<0.05), and USP22 was positively correlated with the expressions of MRP1 and P-gp in colorectal cancer tissues (r₁=0.377, r₂=0.423, both P<0.05). Conclusions: The up-regulation of USP22 is related to the acquired resistance of colorectal cancer cells to oxaliplatin. USP22 may be involved in the process of platinum-based chemotherapy resistance of colorectal cancer by regulating the expressions of P-gp and MRP1.

PMID:34954996 | DOI:10.3760/cma.j.cn112137-20210428-01023

Zhonghua Liu Xing Bing Xue Za Zhi. 2021 Dec 10;42(12):2234-2238. doi: 10.3760/cma.j.cn112338-20210430-00361.

ABSTRACT

Data mining has been widely used in the study of cardiovascular disease prognosis. For stroke prognosis, the focus was mainly on the prediction of intervention effectiveness. In contrast, the focus was primarily on predicting natural prognostic and intervention safety for other cardiovascular diseases. In addition, compared with traditional statistical methods, machine learning, especially deep learning based on neural networks has much better performance in predicting the prognosis of cardiovascular diseases, which is worthy of further promotion and application. Therefore, this study systematically reviewed the recent application progress of data mining in cardiovascular disease prognosis, summarized the shortcomings of current studies, and put forward future directions.

PMID:34954992 | DOI:10.3760/cma.j.cn112338-20210430-00361