Accumulating studies have suggested that targeting transcription factor EB (TFEB), an essential regulator of autophagy‐lysosomal pathway (ALP), is promising for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, potent and specific small molecule TFEB activators are not available at present. Previously, we identified a novel TFEB activator named curcumin analog C1 which directly binds to and activates TFEB. In this study, we systematically investigated the efficacy of curcumin analog C1 in three AD animal models that represent beta‐amyloid precursor protein (APP) pathology (5xFAD mice), tauopathy (P301S mice) and the APP/Tau combined pathology (3xTg‐AD mice). We found that C1 efficiently activated TFEB, enhanced autophagy and lysosomal activity, and reduced APP, APP C‐terminal fragments (CTF‐β/α), β‐amyloid peptides and Tau aggregates in these models accompanied by improved synaptic and cognitive function. Knockdown of TFEB and inhibition of lysosomal activity significantly inhibited the effects of C1 on APP and Tau degradation in vitro. In summary, curcumin analog C1 is a potent TFEB activator with promise for the prevention or treatment of AD.

BACKGROUND/OBJECTIVES Mind‐body exercise has positive effects on cognitive performance, according to clinical observation and experts’ recommendations. However, its potential benefits for the cognitive function of aging adults are uncertain and still lack systematic estimations. Therefore, we conducted a systematic review and meta‐analysis to evaluate the overall efficacy and effectiveness of mind‐body exercises for cognitive performance in aging individuals with or without cognitive impairment. DESIGN A systematic review and meta‐analysis. SETTING AND PARTICIPANTS We searched related trials through June 2018 from four databases: Medline, Embase, PsycINFO (all via Ovid), and the Cochrane Library/Central Register of Controlled Trials. MEASUREMENTS Methodological quality was assessed using the Cochrane Risk of Bias Tool. A meta‐analysis of comparative effects was performed using Review Manager v.5.3 software, and publication bias was examined using Egger's test. RESULTS A total of 32 randomized controlled trials with 3624 participants were ultimately included in this meta‐analysis. The results revealed that mind‐body exercises as a whole had benefits in improving global cognition compared with that of the control group (mean difference [MD] = 0.92; 95% confidence interval [CI] = 0.33‐1.51; p = .002) and were more effective than control interventions in promoting cognitive flexibility (MD = −8.80; 95% CI = −15.22 to −2.38; p = .007), working memory (MD = 0.32; 95% CI = 0.01‐0.64; p = .05), verbal fluency (standardized mean difference [SMD] = 0.27; 95% CI = 0.09‐0.45; p = .003), and learning (SMD = 0.24; 95% CI = 0.10‐0.39; p = .001) on cognitively intact or impaired older adults. In dose‐subgroup analysis, only moderate exercise intensity (60‐120 min per week) significantly increased global cognition scores compared with those of the control group (MD = 1.15; 95% CI = 0.34‐1.97; p = .006). CONCLUSION Mind‐body exercises, especially tai chi and dance mind‐body exercise, are beneficial for improving global cognition, cognitive flexibility, working memory, verbal fluency, and learning in cognitively intact or impaired older adults. Moderate intensity is recommended as the optimal dose for older adults. J Am Geriatr Soc 67:749–758, 2019.

Nenggui Xu and colleagues call for more effective evidence dissemination of and research into promising acupuncture therapies

Background The aim of this study was to assess the passive stiffness of the medial and lateral gastrocnemius (MG and LG), Achilles tendon (AT), and plantar fascia (PF) at different ankle and knee positions. Material/Methods Stiffness was assessed using a portable hand-held device (MyotonPRO). In 30 healthy participants (15 males, 15 females) with the knee fully extended or flexed 90°, stiffness of the MG, LG, AT, and PF was measured at 50° plantar flexion, 0° (neutral position), and 25° dorsiflexion (not for AT) of the ankle joint by passive joint rotation. Results With the knee fully extended, passive dorsiflexion caused significant increase in muscle stiffness ( P <0.001), whereas AT and PF stiffness increased with passive ankle dorsiflexion regardless of knee position ( P <0.001). Increased stiffness was observed in MG compared to LG ( P <0.001) and at the 3-cm site of AT compared to the 6-cm site ( P <0.05). Stiffness was greater in LG compared to MG at −50° plantar flexion ( P <0.001) and was greater in MG compared to LG at 25° dorsiflexion ( P <0.05). Stiffness of AT increased in a distal-to-proximal pattern: 0 cm >3 cm >6 cm ( P <0.001). Conclusions Stiffness assessed by use of the MyotonPRO was similar assessments using other techniques, suggesting that the MyotonPRO is capable of detecting the variations in stiffness of MG, LG, AT, and PF at different ankle and knee positions.

Diarrhea-predominant irritable bowel syndrome (IBS-D) and functional diarrhea (FD) are highly prevalent, and the effectiveness of acupuncture for managing IBS-D and FD is still unknown.The aim of this study was to compare the effectiveness of electroacupuncture with loperamide.It was a prospective, randomized, parallel group controlled trial.A total of 448 participants were randomly assigned to He electroacupuncture group (n = 113), Shu-Mu electroacupuncture group (n = 111), He-Shu-Mu electroacupuncture group (n = 112), or loperamide group (n = 112). Participants in the 3 acupuncture groups received 16 sessions of electroacupuncture during a 4-week treatment phase, whereas participants in the loperamide group received oral loperamide 2 mg thrice daily. The primary outcome was the change from baseline in stool frequency at the end of the 4-weeks treatment. The secondary outcomes were the Bristol scale, the MOS 36-item short form health survey (SF-36), the weekly average number of days with normal defecations and the proportion of adverse events.Stool frequency was significantly reduced at the end of the 4-week treatment in the 4 groups (mean change from baseline, 5.35 times/week). No significant difference was found between the 3 electroacupuncture groups and the loperamide group in the primary outcome (He vs. loperamide group [mean difference 0.6, 95% CI, –1.2 to 2.4]; Shu-Mu vs. loperamide group [0.4, 95% CI, –1.4 to 2.3]; He-Shu-Mu vs. loperamide group [0.0, 95% CI, –1.8 to 1.8]). Both electroacupuncture and loperamide significantly improved the mean score of Bristol scale and increased the weekly average number of days with normal defecations and the mean scores of SF-36; they were equivalent in these outcomes. However, the participants in electroacupuncture groups did not report fewer adverse events than those in the loperamide group. Similar results were found in a subgroup analysis of separating patients with IBS-D and FD patients.Electroacupuncture is equivalent to loperamide for reducing stool frequency in IBS-D and FD patients. Further studies on cost effectiveness of acupuncture are warranted.

No abstract

Background: Nonpharmacological interventions are the first recommendation for cancerrelated fatigue, according to current guidelines. There are many forms of nonpharmacological interventions for addressing cancer-related fatigue, but the preferred means remain controversial and are not stated in the guidelines. Therefore, we evaluated the comparative effects and ranks of all major nonpharmacological interventions, according to different assessment methods, in cancer patients with fatigue.Methods: Medline, Embase, Cochrane Library, and Allied and Complementary Medicine Database were searched for randomized controlled trials on nonpharmacological treatments for cancer-related fatigue. We assessed the trials' methodological quality using the Cochrane Risk of Bias tool. A Bayesian network meta-analysis and a comparative effects ranking were performed with Aggregate Data Drug Information System software.Results: A total of 16,675 items were obtained from the databases, and 182 studies comprising 18,491 participants were included in the analysis. Based on the ranking probabilities, multimodal therapy and qigong ranked best with a Brief Fatigue Inventory; for a Functional Assessment of Cancer Therapy-fatigue scale, combined psychosocial therapies and bright white light therapy ranked best; for the Piper Fatigue Scale, resistance exercise and mindfulness-based stress reduction ranked best; for a multidimensional fatigue inventory, multimodal therapy and cognitive behavioral therapy (CBT) ranked best; for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), acupuncture and CBT ranked best; and for the Profile of Mood States Fatigue Subscale, multimodal therapy, qigong, aerobic exercise, and CBT ranked best. Comprehensive analysis of the results indicated that multimodal therapy, CBT, and qigong might be the optimum selections for reducing cancer-related fatigue. Most of the included studies had low risk of methodological quality problems; however, 59 studies had low methodological quality.Linking Evidence to Action: Different interventions have their own sets of advantages for addressing cancer-related fatigue. These results can be utilized as evidence-based interventions for healthcare workers and patients to manage cancer-related fatigue.

The aim of the study was to assess the prevalence of human papillomavirus (HPV) in the esophagus in the coastal region of Eastern Guangdong, Southern China, an area with a high incidence of esophageal carcinoma. Fresh surgical resection esophageal specimens were obtained from 176 esophageal carcinoma patients admitted to the Tumor Hospital of Shantou University Medical College. The samples were subjected to polymerase chain reaction (PCR) to detect HPV infection using consensus and type-specific primers for HPV type 6, 11, 16, and 18. The incidence rate was 65.5%, 69.1%, and 60% in tissues of cancerous, paracancerous and normal mucosa, respectively. Further analysis of the distribution of HPV types in the three sections of tissues showed that the high-risk HPV types 16 and 18 were found mainly in the cancer cells (43.2%), whereas the low-risk HPV types 6 and 11 were seen mainly in the normal mucosa (52.3%). The total infection rate of the high-risk HPV types 16 and HPV 18 was the highest in cancerous tissues (54.5%), followed by paracancerous tissues (19.5%), and the lowest in normal mucosa (11.7%). There was high incidence of HPV infection in the esophageal epithelium in Eastern Guangdong, Southern China, where esophageal carcinoma is prevalent. HPV was seen in the normal, paracancerous and cancerous tissues, with the high-risk HPV type 16 and 18 more common in cancerous tissues. The results indicate that the high incidence of esophageal carcinoma in this area is associated with HPV infection.