Taoist Tai Chi® and Memory Intervention for Individuals with Mild Cognitive Impairment.

OBJECTIVE: It was hypothesized that a combined Taoist Tai Chi (TTC) and a memory intervention program (MIP) would be superior to a MIP alone in improving everyday memory behaviors in individuals with amnestic mild cognitive impairment (aMCI). A secondary hypothesis was that TTC would improve cognition, self-reported health status, gait, and balance. METHOD: A total of 48 individuals were randomly assigned to take part in MIP + TTC or MIP alone. The TTC intervention consisted of twenty 90 min sessions. Outcome measures were given at baseline, and after 10 and 22 weeks. RESULTS: Both groups significantly increased their memory strategy knowledge and use, ratings of physical health, processing speed, everyday memory, and visual attention. No preferential benefit was found for individuals in the MIP + TTC group on cognition, gait, or balance measures. CONCLUSIONS: Contrary to expectations, TTC exercise did not specifically improve cognition or physical mobility. Explanations for null findings are explored.

Modeling Human Cytomegalovirus-Induced Microcephaly in Human iPSC-Derived Brain Organoids.

Although congenital infection by human cytomegalovirus (HCMV) is well recognized as a leading cause of neurodevelopmental defects, HCMV neuropathogenesis remains poorly understood. A major challenge for investigating HCMV-induced abnormal brain development is the strict CMV species specificity, which prevents the use of animal models to directly study brain defects caused by HCMV. We show that infection of human-induced pluripotent-stem-cell-derived brain organoids by a "clinical-like" HCMV strain results in reduced brain organoid growth, impaired formation of cortical layers, and abnormal calcium signaling and neural network activity. Moreover, we show that the impeded brain organoid development caused by HCMV can be prevented by neutralizing antibodies (NAbs) that recognize the HCMV pentamer complex. These results demonstrate in a three-dimensional cellular biosystem that HCMV can impair the development and function of the human brain and provide insights into the potential capacity of NAbs to mitigate brain defects resulted from HCMV infection.

An observational study of pain self-management strategies and outcomes: does type of pain, age, or gender, matter?

Background and aims Acute pain is differentiated from chronic pain by its sudden onset and short duration; in contrast, chronic pain is characterized by a duration of at least several months, typically considered longer than normal healing time. Despite differences in definition, there is little information on how types of self-management strategies or outcomes differ when pain is chronic rather than acute. Additionally, age and gender are thought to be related to types of strategies used and outcomes. However, strategies used and outcomes can be influenced by level of education, socioeconomic status, occupation, and access to the health care system, which can confound associations to type of pain, age or gender. The purpose of this study was to examine the association of strategies used for pain self-management and outcomes with type of pain, acute or chronic, age, or gender in a socioeconomically homogenous population, pharmacists. Methods Pharmacists with acute or chronic pain and a valid email completed an on-line questionnaire on demographic characteristics, pain characteristics, pharmacological and non-pharmacological strategies for managing pain, and outcomes (e.g. pain intensity). Univariate analysis was conducted by stratifying on type of pain (acute or chronic), then stratifying on gender (men vs. women) and age (younger vs. older). The a priori alpha level was 0.05. Results A total of 366 pharmacists completed the questionnaire, 212 with acute pain (average age=44±12.1; 36% men) and 154 with chronic pain (average age=53±14.0; 48% men). The chronic pain group reported substantially higher levels of pain before treatment, level of post-treatment pain, level of pain at which sleep was possible, and goal pain levels (effect sizes [ES's]=0.37-0.61). The chronic pain group were substantially more likely to use prescription non-steroidal anti-inflammatory medications (NSAIDS), opioids, and non-prescription pain relievers (ES's=0.29-0.80), and non-medical strategies (ES's=0.56-0.77). Participants with chronic pain also were less confident (ES=0.54) and less satisfied (ES=0.52). In contrast, there were no differences within either the acute or chronic pain groups related to gender and outcomes. In the acute pain group, there also were no gender differences related to management strategies. However, younger age in the acute pain group was associated with use of herbal remedies and use of rest. Within the chronic pain group, men were more likely to use NSAIDS and women more likely to use hot/cold packs or massage while older participants were more likely to use massage. Variability in post-treatment level of pain and percent relief was high in all groups (coefficient of variation=25%-100%). Conclusions The differences between acute and chronic pain were substantial and included differences in demographic characteristics, pain characteristics, management strategies used, and outcomes. In contrast, few associations between age and gender with either management strategies or outcomes were identified, although the variability was high. Implications When managing or researching pain management, acute pain should be differentiated from chronic pain. Because of the substantial variability within the gender and age groups, an individual approach to pain management irrespective of age and gender may be most useful.

The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model.

Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation.