Radically different
The dynamic regulation of neuronal polarity is essential for the formation of neural networks during brain development. Primary cultures of rodent neurons recapitulate several aspects of this polarity regulation, providing valuable insights into the molecular mechanisms underlying axon specification, dendrite formation, and neuronal migration. However, the process by which the preexisting bipolarity of migrating neurons is disrupted to form multipolar dendrites remains to be elucidated. In this study, we demonstrate that MTCL2, a microtubule-crosslinking protein associated with the Golgi apparatus, plays a crucial role in this type of polarity transformation exhibited by cerebellar granule neurons (CGNs) in mice of either sex. MTCL2 is highly expressed in CGNs and gradually accumulates in dendrites as the cells develop polarity. MTCL2 knockdown inhibited the bipolar-to-multipolar transition of dendrite extension observed in their differentiation in vitro as well as in vivo. During this transformation, the Golgi apparatus shifts from the base of the preexisting bipolar neurites to the lateral or apical side of the nucleus in the cell body. There, it forms a close association with the microtubule cage that wraps around the nucleus. The resulting upward extension of the Golgi apparatus is tightly coupled with the randomization of its position in the x–y plane. Knockdown and rescue experiments demonstrated MTCL2 promotes these changes in the Golgi position in a microtubule- and Golgi-binding activity-dependent manner. These results suggest that MTCL2 promotes the development of multipolar short dendrites by sequestering the Golgi apparatus from the base of the preexisting neurite into the microtubule cage.
Background: Women living in rural agrarian reform communities face intersecting challenges related to social, economic, racial, and gender vulnerabilities, which significantly increase their likelihood of developing physical and mental health problems. Despite the potential of telephone-based interventions to promote mental health, there is a lack of studies assessing their feasibility and effectiveness among underserved populations in Brazil. Objective: This study aimed to assess the feasibility and effectiveness of a telephone-based intervention on mental health outcomes among women living in a rural agrarian reform community in Brazil. Methods: We conducted a descriptive, prospective pilot study with a pretest and posttest design. Data were collected at 3 time points: baseline, 1 week, and 1 month after the intervention. The outcomes assessed included quality of life, social support, self-efficacy, and common mental disorder symptoms. Nonparametric tests were used to analyze the data. The intervention consisted of 3 phone calls supported by a workbook, with content based on cognitive behavioral and psychiatric nursing principles. Results: Of the 31 women enrolled, 23 (74.2%) completed all 3 phone-based sessions. There was a significant reduction in common mental disorder symptoms (Kendall =0.280; =.002), particularly in the somatic domain (=.02). Moreover, participants reported improved perceptions of the physical domain of quality of life (Kendall =0.131; =.049). All women rated the intervention positively, with more than half emphasizing its practical usefulness. Conclusions: The telephone-based intervention was feasible and showed promising results in improving mental health outcomes among women in a rural setting. These findings support integrating low-intensity, remote psychosocial strategies into primary health care, especially those led by nurses, to increase access to mental health promotion for vulnerable populations.
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Background: Digital mental health technologies (DMHTs) are playing an increasing role in mental health services. The quality of evidence for DMHTs is variable, and there are concerns that evidence is not sufficient to support decision-making. Objective: This study used a cross-sectional analysis of evidence supporting DMHTs included in National Institute for Health and Care Excellence (NICE) evaluations to examine the strength of evidence available for decision-making. Methods: We identified all NICE evaluations relating to DMHTs by reviewing details of published NICE evaluations on the NICE website. From each of these evaluations, we identified included DMHTs and reviewed committee documentation to identify studies that provided supporting evidence for each of these technologies. We extracted information on a series of items relating to study quality and summarized the characteristics of evidence both at the level of individual studies and across the package of evidence from multiple studies supporting DMHTs. We also identified key evidence gaps in available evidence. Results: We included nine NICE evaluations relating to anxiety, depression, psychosis, insomnia, attention deficit hyperactivity disorder (ADHD), and tic disorders. These evaluations included 30 DMHTs and referenced 78 supporting studies. We identified common evidence gaps relating to effectiveness compared to relevant comparators, use of appropriate outcomes, including health-related quality of life, cost of delivery, and impact on resource use, and reporting of adverse events. Conclusions: Our study highlights that some DMHTs have been supported by high-quality studies and that evidence to support DMHTs is likely to be developed across a series of studies. However, there are often key evidence gaps that need to be addressed to provide a stronger case for adoption. Developers should ensure that they consider these gaps while planning evidence generation, and where possible, address them earlier in the product lifecycle.
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