Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II.

Glutaric aciduria type II (GA II) is an autosomal recessive metabolic disorder of fatty acid, amino acid, and choline metabolism. The late-onset form of this disorder is caused by a defect in the mitochondrial electron transfer flavoprotein dehydrogenase or the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Thus far, the high clinical heterogeneity of late-onset GA II has brought a great challenge for its diagnosis. In this study, we reported a 21-year-old Chinese man with muscle weakness, vomiting, and severe pain. Muscle biopsy revealed myopathological patterns of lipid storage myopathy, and urine organic acid analyses showed a slight increase in glycolic acid. All the aforementioned results were consistent with GA II. Whole-exome sequencing (WES), followed by bioinformatics and structural analyses, revealed two compound heterozygous missense mutations: c.1034A > G (p.H345R) on exon 9 and c.1448C>A (p.P483Q) on exon 11, which were classified as "likely pathogenic" according to American College of Medical Genetics and Genomics (ACMG). In conclusion, this study described the phenotype and genotype of a patient with late-onset GA II. The two novel mutations in ETFDH were found in this case, which further expands the list of mutations found in patients with GA II. Because of the treatability of this disease, GA II should be considered in all patients with muscular symptoms and acute metabolism decompensation such as hypoglycemia and acidosis.

Astaxanthin Ameliorates Worsened Muscle Dysfunction of MDX Mice Fed with a High-Fat Diet through Reducing Lipotoxicity and Regulating Gut Microbiota.

Duchenne muscular dystrophy (DMD), a severe X-linked inherited neuromuscular disease, has a high prevalence of obesity. Obesity exacerbates muscle damage and results in adverse clinical outcomes. Preventing obesity helps DMD patients delay disease progression and improve quality of life. Astaxanthin (AX) is a kind of carotenoid which has antioxidant and anti-adipogenesis effects. In this study, male C57BL/10ScSnDmdmdx/J mice were fed with a normal diet, a high-fat diet (HFD), and an HFD containing AX for 16 weeks, respectively. The results showed that AX significantly increased gastrocnemius fiber cross-section area and grip strength, improved treadmill endurance test and mitochondrial morphology, and reduced muscle triglyceride and malonaldehyde levels compared to the HFD. Lipidomic analysis revealed that AX decreased high levels of triglyceride, diglyceride, ceramides, and wax ester induced by HFD. Gut microbiota analysis indicated that AX supplementation failed to alleviate abnormal microbiota diversity, but increased the relative abundances of Akkermansia, Bifidobacterium, Butyricicoccus, and Staphylococcus. In conclusion, AX was expected to alleviate disease progression associated with obesity in DMD patients by reducing lipotoxicity and increasing the abundance of beneficial bacteria.

Effects of Virtual Reality Rehabilitation Training on Cognitive Function and Activities of Daily Living of Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the effects of virtual reality (VR) rehabilitation training on the cognitive function and activities of daily living (ADL) of patients with poststroke cognitive impairment (PSCI). DATA SOURCES: Four Chinese databases and 6 English databases were systematically searched for studies published until August 31, 2021, by using Medical Subject Headings of the National Library of Medicine terms such as virtual reality, cognition disorders, cognitive dysfunction, and stroke and free terms such as virtual environment, VR, cognition impairment, cerebrovascular accident, and PSCI. STUDY SELECTION: Randomized controlled trials treating PSCI with VR training were included. The control groups received conventional treatments such as conventional rehabilitation training and drug therapy; the experimental groups received VR rehabilitation training. The outcome measures were cognitive function and ADL. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. Meta-analysis was performed using RevMan v5.4. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. DATA SYNTHESIS: Twenty-one studies (1149 participants) were included. Meta-analyses found that compared with the control group, VR rehabilitation training increased Mini-Mental State Examination, Montreal Cognitive Assessment, Loewenstein Occupational Therapy Cognitive Assessment, Rivermead Behavioral Memory Test Second Edition, Barthel Index, Modified Barthel Index, and FIM scores; event-related potential 300 (P300) amplitude; and the N-acetylaspartate/creatinine (Cr) ratio on proton magnetic resonance spectroscopy (1H-MRS) and reduced P300 latency; Trail Making Test scores; and the choline-containing compounds/Cr ratio on 1H-MRS (all P<.05). These results indicated that VR training improved cognitive function and ADL in PSCI. CONCLUSIONS: VR rehabilitation training promotes the rehabilitation of cognitive function and recovery of ADL in patients with PSCI and may be a good complementary approach to conventional cognitive interventions.

Can Tai Chi Improve Cognitive Function? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Tai Chi (TC) is a traditional Chinese martial art with demonstrated beneficial effects on physical and mental health. In this study, the authors performed a systematic review to assess the efficiency of TC in different populations' cognitive function improvement. Design: The present systematic review utilized the Chinese National Knowledge Infrastructure (1915-), Wanfang (1998-), VIP (1989-), Chinese Biomedicine databases (1978-), PubMed (1950-), Web of Science (1900-), Cochrane Library (1948-), Embase (1974-), EBSCOhost (1922-), and OVID (1996-) databases to search and identify relevant articles published in English and Chinese from the beginning of coverage through October 17, 2020. Randomized controlled trials (RCTs) published from the beginning of coverage through October 17, 2020 in English and Chinese were retrieved from many indexing databases. Selected studies were graded according to the Cochrane Handbook for Systematic Reviews of Intervention 5.1.0. The outcome measures of cognitive function due to traditional TC intervention were obtained. Meta-analysis was conducted by using RevMan 5.4 software. We follow the PRISMA 2020 guidelines. Results: Thirty-three RCTs, with a total of 1808 participants, were included. The study showed that TC could progress global cognition when assessed in middle-aged as well as elderly patients suffering from cognitive and executive function impairment. The findings are as follows: Montreal Cognitive Assessment Scale: mean difference (MD) = 3.23, 95% CI = 1.88-4.58, p < 0.00001, Mini-Mental State Exam: MD = 3.69, 95% CI = 0.31-7.08, p = 0.03, Trail Making Test-Part B: MD = -13.69, 95% CI = -21.64 to -5.74, p = 0.0007. The memory function of older adults assessed by the Wechsler Memory Scale was as follows: MD = 23.32, 95% CI = 17.93-28.71, p < 0.00001. The executive function of college students evaluated by E-prime software through the Flanker test was as follows: MD = -16.32, 95% CI = -22.71 to -9.94, p < 0.00001. Conclusion: The TC might have a positive effect on the improvement of cognitive function in middle-aged and elderly people with cognitive impairment as well as older adults and college students.

Systematic review and meta-analysis of randomized controlled trials assessing the impact of Baduanjin exercise on cognition and memory in patients with mild cognitive impairment.

OBJECTIVE: To determine the effectiveness of Baduanjin exercise in improving cognition and memory in patients with mild cognitive impairment. DATA SOURCES: Relevant English- and Chinese-language studies published until 15th September 2020 were retrieved from the PubMed, Web of Science, Cochrane Library, Embase, EBSCOhost, OVID, National Knowledge Infrastructure, WANFANG DATA, VIP Information, and SinoMed databases. REVIEW METHODS: Randomized controlled trials assessing Baduanjin exercise in patients with mild cognitive impairment were included. Two researchers independently identified eligible studies and extracted data. Risk-of-bias assessment was performed using the Cochrane Risk of Bias Tool. RESULTS: This study included 16 randomized controlled trials (1054 participants) from China that used Chinese versions of standardized tests. Most studies had no significant bias, and only one study had a high risk of bias in the random allocation category. Compared with conventional therapy alone, Baduanjin plus conventional therapy significantly improved the Montreal Cognitive Assessment and Mini-Mental State Examination scores after 6 months of treatment (P < 0.00001 for both), significantly decreased the tau/Aß1-42 ratio in the cerebrospinal fluid (P < 0.00001), and significantly improved some dimensional scores on the Wechsler Memory Scale and the auditory verbal learning test scores at 6 months (P < 0.05 for all). CONCLUSION: Compared with conventional therapy, Baduanjin plus conventional therapy significantly improved cognitive and memory function in patients with mild cognitive impairment.

Comparison of regional and local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: Arteriovenous fistulae (AVF) are the hemodialysis access modality of choice for patients with end-stage renal disease. However, they have a high early failure rate. Good vascular access is essential to manage long-term hemodialytic treatment, but some anesthesia techniques directly affect venous diameter as well as intra- and post-operative blood flow. The main purpose of this meta-analysis was to compare the results of regional and local anesthesia (RA and LA) for arteriovenous fistula creation in end-stage renal disease. METHODS: We conducted a systematic review and meta-analysis to synthesize evidence from 7 randomized controlled trials (565 patients) and 1 observational study (408 patients) with the aim of evaluating the safety and efficacy of RA versus LA in surgical construction of AVF. RESULTS: Pooled data showed that RA was associated with higher primary patency rates than LA (odds ratio [OR], 1.88; 95% confidence interval [CI]: 1.24-2.84; P = 0.003; I2 = 31%). Additionally, brachial artery diameter was significantly increased in the RA versus LA group (mean difference [MD], 0.83; 95% CI: 0.75-0.92; P < 0.001; I2 = 97%) and the need for intra- as well as post-operative pain killers was significantly less (RA, P = 0.0363; LA, P = 0.0318). Moreover, operation duration was significantly reduced using RA versus LA (MD, - 29.63; 95% CI: - 32.78 - -26.48; P < 0.001; I2 = 100%). CONCLUSIONS: This meta-analysis suggests that RA is preferable to LA in patients with end-stage renal disease in guaranteeing AVF patency and increasing brachial artery diameter.

Uptake of metronidazole by human gingival fibroblasts.

BACKGROUND: Metronidazole is an important antimicrobial agent for the therapeutic management of periodontal diseases and dentoalveolar infections. As in other tissues, the metronidazole concentration in gingival crevicular fluid is about equal to the plasma level. Thus, we hypothesized that metronidazole is not actively transported into human gingival fibroblasts. METHODS: Using high performance liquid chromatography, the influences of extracellular metronidazole concentrations, temperature, pH, and inhibitors of transporters on the uptake of metronidazole by cultured human gingival fibroblasts were tested. RESULTS: Metronidazole was taken up rapidly by fibroblasts; the intracellular metronidazole concentration reached the extracellular level in 3 minutes at 37 degrees C and in 2 minutes at 4 degrees C. The uptake of metronidazole by human gingival fibroblasts was not saturable, and the intracellular metronidazole concentrations increased linearly with the extracellular level. Temperature and pH had no significant influence on the uptake of metronidazole by fibroblasts. Probenecid and adenine had no influence on the uptake of metronidazole by fibroblasts. These findings indicate that metronidazole uptake does not involve a transporter. Metronidazole bound rapidly to human gingival fibroblasts, but the cell-associated drug declined progressively until it reached a stable plateau in 15 minutes. CONCLUSIONS: Metronidazole rapidly entered human gingival fibroblasts via simple diffusion. Metronidazole easily reached the minimal inhibitory concentration in fibroblasts and gingiva. Given the fact that intracellular concentrations of metronidazole in other tissues and cells are also close to the plasma level, we speculate that metronidazole enters other tissues and cells via simple diffusion.