Can transcranial direct current stimulation combined with interactive computerized cognitive training boost cognition and gait performance in older adults with mild cognitive impairment? a randomized controlled trial.

BACKGROUND: Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI. METHOD: Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions. RESULTS: The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT. CONCLUSION: The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI. TRIAL REGISTRATION: This trial was registered at http://www. CLINICALTRIALS: in.th/ (TCTR 20,220,328,009).

Review articles (Meta-Analyses) effects of walking on cognitive function in individuals with mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Previous studies have shown that regular exercise can improve cognition and physical performance in older adults. Walking is a low-technology and low-cost exercise that has been proven to improve cognition and mobility in healthy elderly individuals. However, no systematic review or meta-analysis has explored whether walking can improve cognitive function in older adults with MCI. This study aimed to explore the effects of walking interventions on cognitive functions in individuals with MCI. METHODS: In accordance with the PRISMA guidelines, MEDLINE, PubMed, SPORTDiscus, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, Airiti Library, and the National Digital Library of Theses and Dissertations in Taiwan were searched from inception to July 2023. Independent reviewers selected randomized clinical trials (RCT) that compared the effects of walking with no intervention or other exercises in individuals with MCI. The primary outcomes were cognitive functions, and the secondary outcome was walking endurance. Three reviewers independently conducted data extraction. The risk of bias was assessed using the Revised Cochrane Risk of Bias assessment tool. RESULTS: Fourteen RCTs were included in this review. The quality of evidence in these studies was rated as good to excellent. The results of the meta-analysis showed that the individuals with MCI had no significant improvement in cognitive function but had significant improvement in the 6-min walk test (Mean Difference=23.70, p=0.008) after walking interventions compared to no intervention or other exercises. CONCLUSION: Walking intervention has no significant improvement on cognitive functions in older adults with MCI. However, walking induces beneficial effects on aerobic capacity. TRIAL REGISTRATION: This systematic review has the registration number CRD42021283753 on PROSPERO.

[The Effects of the Question Prompt List on Usefulness, Satisfaction and Anxiety in Patients With Terminal Cancer: A Meta-Analysis].

BACKGROUND: Difficulties and anxiety caused by poor communication between patients with terminal cancer and their caregivers and medical teams are common in clinical practice. This may lead to uncertainty and fear of treatment, affecting the progress of treatment and achievement of hospice-care goals. The results of prior research indicate that using a question prompt list to promote shared decision-making can improve communication between medical care providers and patients. PURPOSE: This study was developed to explore the effectiveness of using question prompt lists in communications with terminal cancer patients and their families in clinical settings in Taiwan. METHODS: A systematic review of the literature using a meta-analysis research design was conducted in this study. Cochrane Risk of Bias Tool 2 was used to assess literature quality. The selected keywords were used to search six databases, including the English-language PubMed, Cochrane Library, Embase, EBSCOhost, and MEDLINE databases and the Chinese-language Airiti Library database. RevMen 5.4 software (the latest version released by the Nordic Cochrane Center in September 2020) was used for data analysis. RESULTS: Applying the question prompt list was found to significantly increase the number of questions asked (MD = 2.45, p = .01) and the usefulness (SMD = 0.25, p = .02). However, no significant changes in consultation time (MD = 4.49, p = .11), satisfaction (MD = 0.08, p = .91), or anxiety (SMD = 0.06, p = .62) were found. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results support that simplifying and focusing the topics of each chapter and theme of the question prompt list based on time of use may allow the list to be used effectively in combination with family meetings in clinical practice and to be focused based on patient, caregiver, and family needs to facilitate more-productive discussions. This will allow meetings to better facilitate therapeutic relationships and patient and caregiver participation in treatment plans. An external communication coach may be added in the future to help patients and caregivers clarify needs and concerns and improve the effectiveness of consultations. As questioning skills are important to empowering patients, a question prompt list for patients with terminal cancer should be developed. The results of this study may be used to guide the practice of healthcare providers and referenced in caregiver in-service education.

Associations between blood-based biomarkers of Alzheimer's disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aß42 and total tau.

Background: Motoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer's disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aß42 and total tau) and their relationships with cognition in individuals with MCR. Materials and methods: This was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aß42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed. Results: The levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group. Conclusion: In this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies.

Prediction of Cognitive Degeneration in Parkinson's Disease Patients Using a Machine Learning Method.

This study developed a predictive model for cognitive degeneration in patients with Parkinson's disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.

Factors Associated with Fear of Falling in Individuals with Different Types of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is considered an intermediate state between normal aging and early dementia. Fear of falling (FOF) could be considered a risk indicator for falls and quality of life in individuals with MCI. Our objective was to explore factors associated with FOF in those with MCI due to Alzheimer's disease (AD-MCI) and mild cognitive impairment in Parkinson's disease (PD-MCI). Seventy-one participants were separated into two groups, AD-MCI (n = 37) and PD-MCI (n = 34), based on the disease diagnosis. FOF was assessed using the Activities-specific Balance Confidence scale. The neuropsychological assessment and gait assessment were also measured. FOF was significantly correlated with global cognitive function, attention and working memory, executive function, Tinetti assessment scale scores, gait speed, and stride length in the AD-MCI group. Moreover, attention and working memory were the most important factors contributing to FOF. In the PD-MCI group, FOF was significantly correlated with gait speed, and time up and go subtask performance. Furthermore, turn-to-walk was the most important factor contributing to FOF. We noted that FOF in different types of MCI was determined by different factors. Therapies that aim to lower FOF in AD-MCI and PD-MCI populations may address attention and working memory and turn-to-walk, respectively.

Metformin, Rapamycin, or Nicotinamide Mononucleotide Pretreatment Attenuate Cognitive Impairment After Cerebral Hypoperfusion by Inhibiting Microglial Phagocytosis.

Vascular cognitive impairment (VCI) is the second leading form of dementia after Alzheimer's disease (AD) plaguing the elder population. Despite the enormous prevalence of VCI, the biological basis of this disease has been much less well-studied than that of AD, with no specific therapy currently existing to prevent or treat VCI. As VCI mainly occurs in the elderly, the role of anti-aging drugs including metformin, rapamycin, and nicotinamide mono nucleotide (NMN), and the underlying mechanism remain uncertain. Here, we examined the role of metformin, rapamycin, and NMN in cognitive function, white matter integrity, microglial response, and phagocytosis in a rat model of VCI by bilateral common carotid artery occlusion (BCCAO). BCCAO-induced chronic cerebral hypoperfusion could cause spatial working memory deficits and white matter lesions (WMLs), along with increasing microglial activation and phagocytosis compared to sham-operated rats. We found the cognitive impairment was significantly improved in BCCAO rats pretreated with these three drugs for 14 days before BCCAO compared with the vehicle group by the analysis of the Morris water maze and new object recognition tests. Pretreatment of metformin, rapamycin, or NMN also increased myelin basic protein (MBP, a marker for myelin) expression and reduced SMI32 (a marker for demyelinated axons) intensity and SMI32/MBP ratio compared with the vehicle group, suggesting that these drugs could ameliorate BCCAO-induced WMLs. The findings were confirmed by Luxol fast blue (LFB) stain, which is designed for staining myelin/myelinated axons. We further found that pretreatment of metformin, rapamycin, or NMN reduced microglial activation and the number of M1 microglia, but increased the number of M2 microglia compared to the vehicle group. Importantly, the number of MBP+/Iba1+/CD68+ microglia was significantly reduced in the BCCAO rats pretreated with these three drugs compared with the vehicle group, suggesting that these drugs suppress microglial phagocytosis. No significant difference was found between the groups pretreated with metformin, rapamycin, or NMN. Our data suggest that metformin, rapamycin, or NMN could protect or attenuate cognitive impairment and WMLs by modifying microglial polarization and inhibiting phagocytosis. The findings may open a new avenue for VCI treatment.

Effects of Exergaming-Based Tai Chi on Cognitive Function and Dual-Task Gait Performance in Older Adults With Mild Cognitive Impairment: A Randomized Control Trial.

Background: Declined cognitive function interferes with dual-task walking ability and may result in falls in older adults with mild cognitive impairment (MCI). The mind-body exercise, Tai Chi (TC), improves cognition and dual-task ability. Exergaming is low-cost, safe, highly scalable, and feasible. Whether the effects of exergaming-based TC is beneficial than traditional TC has not been investigated yet. Objectives: The objective of this study was to investigate effects of exergaming-based TC on cognitive function and dual-task walking among older adults with MCI. Methods: Fifty patients with MCI were randomly assigned to an exergaming-based TC (EXER-TC) group, a traditional TC (TC) group, or a control group. The EXER-TC and TC groups received 36 training sessions (three, 50-min sessions per week) during a 12-week period. The control group received no intervention and were instructed to maintain their usual daily physical activities. The outcome variables measured included those related to cognitive function, dual-task cost (DTC), and gait performance. Results: The EXER-TC and TC groups performed better than the control group on the Chinese version of the Stroop Color and Word Test, the Trail Making Test Parts A and B, the one-back test, gait speed, and DTC of gait speed in cognitive dual-task conditions after training. However, there were no significant differences between the EXER-TC and TC groups. Compared with the control group, only the EXER-TC group experienced beneficial effects for the Montreal Cognitive Assessment. Conclusion: EXER-TC was comparable to traditional TC for enhancement of dual-task gait performance and executive function. These results suggested that the EXER-TC approach has potential therapeutic use in older adults with MCI.

Plasma total tau predicts executive dysfunction in Parkinson's disease.

OBJECTIVES: Cognitive impairment is an important non-motor aspect of Parkinson's disease (PD). Amyloid-ß and tau pathologies are well-established in Alzheimer's disease and commonly coexist with synucleinopathy in PD. However, the levels of these biomarkers in the plasma of patients with PD and their relationship with specific cognition domains remain to be clarified. The current study compared the motor severity and neuropsychological assessment of general and specific cognition, with plasma levels of α-synuclein (α-syn), amyloid-ß 42 (Aß42), and total tau (t-tau) in PD subjects. METHODS: Plasma levels of α-syn, Aß42, and t-tau were measured in 55 participants with PD through immunomagnetic reduction assay. The evaluation of motor severity and comprehensive neuropsychological assessment was performed in all participants. RESULTS: The level of plasma α-syn was negatively correlated with the scores of Unified Parkinson's Disease Rating Scale part III [r = (-.352), p = .008]. The level of plasma t-tau was negatively correlated with the scores of digits recall forwards and digits recall backwards [r = (-.446), p = .001; r = (-.417), p = .002, respectively]. No correlations were found between the levels of α-syn and Aß42 and any neuropsychological tests. CONCLUSIONS: This study concluded a lower level of plasma α-syn was correlated with motor dysfunction in PD patients, and a higher level of plasma t-tau was correlated with lower cognitive performance, especially for attention and executive function. These results propose the possibility of using plasma biomarkers to predict specific cognitive performance in PD subjects.

Corrigendum: Associations between blood-based biomarkers of Alzheimer's disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aß42 and total tau.

[This corrects the article DOI: 10.3389/fnagi.2022.981632.].

Do cognitive performance and physical function differ between individuals with motoric cognitive risk syndrome and those with mild cognitive impairment?

BACKGROUND: Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. METHODS: A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into 2 groups, MCR (n = 33) and MCI (n = 44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, "pure" MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, and language, were measured. Physical functions such as activities in daily living, the Tinetti Assessment Scale, and the Timed Up and Go test were also measured. RESULTS: Executive function, attention, working memory, episodic memory and language were all significantly lower in the MCR group than the MCI group. Abilities related to physical function, including those measured by the Tinetti Assessment Scale and the Timed Up and Go test, were significantly lower in the MCR group than the MCI group. CONCLUSIONS: We noted that cognitive performance and physical function were lower in MCR individuals than MCI but without MCR syndrome. However, the conclusions were based on the enrollment procedure of participants prioritizes the MCR syndrome. Because of the overlap of MCR and MCI, future studies should use different enrollment strategies to further clarify the status of these two populations.

Indirect Pathway Metabolic Engineering Strategies for Enhanced Biosynthesis of Hyaluronic Acid in Engineered Corynebacterium glutamicum.

Hyaluronic acid (HA) is composed of alternating d-glucuronic acid and N-acetyl-d-glucosamine, with excellent biocompatibility and water retention capacity. To achieve heterologous biosynthesis of HA, Corynebacterium glutamicum, a safe GRAS (generally recognized as safe) host, was utilized and metabolically engineered previously. In this work, to achieve further enhancement of HA yield, four strategies were proposed and performed separately first, i.e., (1) improvement of glucose uptake via iolR gene knockout, releasing the inhibition of transporter IolT1/IolT2 and glucokinases; (2) intensification of cardiolipin synthesis through overexpression of genes pgsA1/pgsA2/cls involved in cardiolipin synthesis; (3) duly expressed Vitreoscilla hemoglobin in genome, enhancing HA titer coupled with more ATP and improved NAD+/NADH (>7.5) ratio; and (4) identification of the importance of glutamine for HA synthesis through transcriptome analyses and then enhancement of the HA titer via its supplement. After that, we combined different strategies together to further increase the HA titer. As a result, one of the optimal recombinant strains, Cg-dR-CLS, yielded 32 g/L of HA at 60 h in a fed-batch culture, which was increased by 30% compared with that of the starting strain. This high value of HA titer will enable the industrial production of HA via the engineered C. glutamicum.

Predicting Cognitive Decline in Parkinson's Disease with Mild Cognitive Impairment: A One-Year Observational Study.

We conducted an observational study to investigate clinical predictors of cognitive decline in patients with mild cognitive impairment (MCI), with a focus on patients with Parkinson's disease (PD) and Alzheimer's disease (AD). The study was performed with detailed neuropsychological testing, a portable device for gait analysis, and a comprehensive geriatric assessment for patients with MCI. Cognitive decline was defined as subjective cognitive impairment with an objective decline in the Mini-Mental State Examination (MMSE) ≥2 points at the one-year follow-up. Participants (n = 74) had a median age of 70 (interquartile range 60-79) years, and 45.9% of them were women. At the end of the study, 17.6% of the patients with MCI had a cognitive decline. Although no differences were observed between groups at the baseline cognitive study, patients with PD-MCI demonstrated more cognitive decline than patients with AD-MCI (28.6% vs. 7.7% p = 0.03). Patients with PD-MCI had more physical disabilities, including scores of instrumental activities of daily living (IADL), Tinetti balance, and gait scores, and some Timed Up and Go components. Initial Clinical Dementia Rating-Sum of Boxes score was a better predictor of future cognitive decline than MMSE in PD-MCI. For predicting the occurrence of cognitive decline in PD-MCI, the prediction accuracy increased from the reduced model (AUC = 0.822, p < 0.001) to the full model (a total of five independent variables, AUC = 0.974, p < 0.001). Given the potentially modifiable predictor, our findings also highlight the importance of identifying sleep quality and the ability to perform IADL.

Enhancing single-cell hyaluronic acid biosynthesis by microbial morphology engineering.

Microbial morphology engineering is a novel approach for cell factory to improve the titer of target product in bio-manufacture. Hyaluronic acid (HA), a valuable glycosaminoglycan polymerized by HA synthase (HAS), a membrane protein, is particularly selected as the model product to improve its single-cell HA-producing capacity via morphology engineering. DivIVA and FtsZ, the cell-elongation and cell division related protein, respectively, were both down/up dual regulated in C. glutamicum via weak promoter substitution or plasmid overexpression. Different from the natural short-rod shape, varied morphologies of engineered cells, i.e. small-ellipsoid-like (DivIVA-reduced), bulb-like (DivIVA-enhanced), long-rod (FtsZ-reduced) and dumbbell-like (FtsZ-enhanced), were observed. Applying these morphology-changed cells as hosts for HA production, the reduced expression of both DivIVA and FtsZ seriously inhibited normal cell growth; meanwhile, overexpression of DivIVA didn't show morphology changes, but overexpression of FtsZ surprisingly change the cell-shape into long and thick rod with remarkably enlarged single-cell surface area (more than 5.2-fold-increase). And finally, the single-cell HA-producing capacity of the FtsZ-overexpressed C. glutamicum was immensely improved by 13.5-folds. Flow cytometry analyses verified that the single-cell HAS amount on membrane was enhanced by 2.1 folds. This work is pretty valuable for high titer synthesis of diverse metabolic products with microbial cell factory.

Effects of Far-Infrared Therapy on Foot Circulation Among Hemodialysis Patients With Diabetes Mellitus.

BACKGROUND: Far-infrared radiation (FIR) therapy improves vessel dilation, circulation, vessel endothelial function, and angiogenesis and reduces atherosclerosis. However, evidence of FIR therapy's effects on foot circulation among diabetic patients undergoing hemodialysis is scarce. AIM: To determine whether FIR therapy improves foot circulation in diabetic patients undergoing hemodialysis. DESIGN: Quasi-experimental. METHODS: In June to November 2017, diabetic patients undergoing hemodialysis (N = 58) at a hemodialysis center in northern Taiwan were divided into two groups: the experimental group (n = 31) received FIR therapy to the bilateral dorsalis pedis artery (40 min/session, 3 times/week for 6 months) and the control group (n = 27) received conventional dialysis care. Paired t test, independent samples t test, two-proportion Z test, and repeated-measures analysis of covariance were performed to compare changes from baseline to the end of the 6-month intervention between the groups. RESULTS: Significant positive effects of FIR therapy on temperature, pulse, and blood flow of the dorsalis pedis artery were observed. Sensitivity to pain, tactility, and pressure also improved significantly in the experimental group. The Edinburgh Claudication Questionnaire revealed that the experimental group had reductions in subjective experiences of soreness, tingling, and coldness in the feet. CONCLUSION: The findings of significant improvements to objective and subjective measures of blood flow and neural function in the experimental group indicate that FIR therapy improves blood circulation to the feet. This therapy thus has great potential to be an effective adjuvant treatment for patients with diabetes mellitus undergoing hemodialysis.

Engineering Corynebacterium glutamicum for high-titer biosynthesis of hyaluronic acid.

Hyaluronic acid (HA) is a member of the glycosaminoglycan family and has been widely used in the clinical, medical, cosmetic and food industries. In this study, we constructed a superior cell factory in Corynebacterium glutamicum for high-titer HA biosynthesis through systematic design and metabolic engineering based on a genome-scale metabolic model, iCW773. The OptForceMUST algorithm was used in iCW773 to determine genetic interventions by using flux balance analysis. Enhancement of the HA biosynthesis pathway and attenuation of the glycolysis pathway, the pentose phosphate pathway and the dehydrogenation of pyruvate were predicted as targets for genetic modulations. Various genetic strategies were employed, including an additional promoter, PdapB, driving hasB expression, antisense RNA-mediated attenuation of fba, zwf deletion and lactate/acetate pathway knockout. The integrated genetic changes in recombinant C. glutamicum produced 24.5 g/L HA in a fed-batch culture. Finally, pyruvate dehydrogenase activity was further reduced by antisense RNA and initial codon mutation to divert carbon flux from byproducts to HA. The corresponding modified strain, CgHA25, achieved a titer of 28.7 g/L. The byproduct concentration was reduced by half, and the major weight-average molecular weight (Mw) component was 0.21 MDa. This work reports a significant improvement in the HA titer in a safe host achieved by systematic metabolic engineering.

Effects of Tai Chi Exercise on Reducing Falls and Improving Balance Performance in Parkinson's Disease: A Meta-Analysis.

INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disorder that may increase the risk of falls, functional limitation, and balance deficits. Tai Chi was used as an option for improving balance in people with PD. The aim of this meta-analysis was to evaluate the effects of Tai Chi on falls, balance, and functional mobility in individuals with PD. METHOD: The literature search was conducted in PubMed, the Cochrane Library, CINAHL, PEDro, Medline, Embase, sportDISCUS, Trip, and the National Digital Library of Theses and Dissertations in Taiwan. Randomized controlled trials (RCTs) analyzing the effects of Tai Chi, compared to no intervention or to other physical training, on falls, functional mobility, and balance in PD patients were selected. The outcome measurements included fall rates, Berg Balance Scale (BBS), Functional Reach (FR) test, and the Timed Up and Go (TUG) test. Two reviewers independently assessed the methodological quality and extracted data from the studies using the PEDro scale. RESULTS: Five RCTs that included a total of 355 PD patients were included in this review. The quality of evidence in these studies was rated as moderate to high. Compared to no intervention or other physical training, Tai Chi significantly decreased fall rates (odds ratio = 0.47, 95% confidence interval (CI) 0.30 to 0.74, and p=0.001) and significantly improved balance and functional mobility (BBS mean difference (MD) = 3.47, 95% CI 2.11 to 4.80, and p < 0.001; FR MD = 3.55 cm, 95% CI 1.88 to 5.23, and p < 0.001; TUG MD = -1.06 s, 95% CI -1.61 to -0.51, and p < 0.001) in people with PD. CONCLUSION: This meta-analysis provides moderate- to high-quality evidence from five RCTs that Tai Chi could be a good physical training strategy for preventing falls and improving balance and functional mobility in people with PD.

Biosynthesis of Chondroitin in Engineered Corynebacterium glutamicum.

Chondroitin, the precursor of chondroitin sulfate, which is an important polysaccharide, has drawn significant attention due to its applications in many fields. In the present study, a heterologous biosynthesis pathway of chondroitin was designed in a GRAS (generally recognized as safe) strain C. glutamicum. CgkfoC and CgkfoA genes with host codon preference were synthesized and driven by promoter Ptac, which was confirmed as a strong promoter via GFPuv reporter assessment. In a lactate dehydrogenase (ldh) deficient host, intracellular chondroitin titer increased from 0.25 to 0.88 g/l compared with that in a wild-type host. Moreover, precursor enhancement via overexpressing precursor synthesizing gene ugdA further improved chondroitin titers to 1.09 g/l. Chondroitin production reached 1.91 g/l with the engineered strain C. glutamicum ΔL-CgCAU in a 5-L fed-batch fermentation with a single distribution Mw of 186 kDa. This work provides an alternative, safe and novel means of producing chondroitin for industrial applications.

Beta event-related desynchronization can be enhanced by different training programs and is correlated with improved postural control in individuals with Parkinson's disease.

BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of a specific exercise (SE) training program focusing on balance and muscle strengthening and a turning-based treadmill (TT) training program on cortical desynchronization and postural control in Parkinson's disease (PD). METHODS: Eighteen patients with PD were recruited and randomly assigned to the SE group, TT training group or control exercise (CE) group and participated in 12 30-min training sessions focusing on balance and strengthening, turning-based treadmill training, or general exercise training, respectively, followed by 10 minutes of over-ground walking in each session for 4 to 6 weeks. The outcomes included alpha event-related desynchronization (ERD), beta ERD, postural control ability indicated by postural instability and gait disorder (PIGD), the step/quick turn test (SQT), and the sensory organization test (SOT). All measurements were assessed at baseline and after training. RESULTS: The results (n=6 for each group) showed that both the SE and TT groups had improved beta ERD, but not alpha ERD, in the Cz area, PIGD score, and turn sway/time in the SQT compared with the CE group. Furthermore, postural control ability was positively correlated with beta ERD in the Cz area. However, there was no significant correlation between SOT total score and alpha ERD in the Cz area. CONCLUSIONS: This study showed that beta ERD in the central area and postural control can be improved with balance training, along with lower extremity muscle strengthening exercise and turning-based treadmill training, in patients with PD. Furthermore, improvement in beta ERD in the central area correlated with improvements in postural control ability. This trial was registered at http://www.anzctr.org.au/ (ACTRN12616000198426).

Enhanced Biosynthesis of Hyaluronic Acid Using Engineered Corynebacterium glutamicum Via Metabolic Pathway Regulation.

Hyaluronic acid (HA) is a polysaccharide used in many industries such as medicine, surgery, cosmetics, and food. To avoid potential pathogenicity caused by its native producer, Streptococcus, efforts have been made to create a recombinant host for HA production. In this work, a GRAS (generally recognized as safe) strain, Corynebacterium glutamicum, is engineered for enhanced biosynthesis of HA via metabolic pathway regulation. Five enzymes (HasA-HasE) involved in the HA biosynthetic pathway are highlighted, and eight diverse operon combinations, including HasA, HasAB, HasAC, HasAD, HasAE, HasABC, HasABD, and HasABE, are compared. HasAB and HasABC are found to be optimal for HA biosynthesis in C. glutamicum. To meet the energy demand for HA synthesis, the metabolic pathway that produces lactate is blocked by knocking out the lactate dehydrogenase (LDH) gene using single crossover homologous recombination. Engineered C. glutamicum/Δldh-AB is superior and had a significantly higher HA titer than C. glutamicum/Δldh-ABC. Batch and fed-batch cultures of C. glutamicum/Δldh-AB are performed in a 5-L fermenter. Using glucose feeding, the maximum HA titer reached 21.6 g L-1 , more than threefolds of that of the wild-type Streptococcus. This work provides an efficient, safe, and novel recombinant HA producer, C. glutamicum/Δldh-AB, via metabolic pathway regulation.