Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

79-85Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

Do family values and reproductive health knowledge influence reproductive health-promoting behaviors in married women? A cross-sectional survey

Purpose Based on the World Health Organization framework on reproductive health, this descriptive correlational study investigated the factors affecting reproductive health-promoting behaviors of married women, with a focus on family values and reproductive health knowledge. Methods A cross-sectional survey was conducted on 170 married women between the ages of 25 and 49 years living in Daegu, Korea. The general and reproductive health characteristics, family values, and reproductive health knowledge of married women were identified, as well as factors affecting reproductive health-promoting behaviors. A questionnaire survey was administered to investigate the impact of various factors on reproductive health-promoting behaviors. Results Positive correlations were shown for health promotion behaviors with family values (r=.78, p<.001) and reproductive health knowledge (r=.55, p<.001). Family values (β=.35, p<.001) and reproductive health knowledge (β=.24, p<.001) were identified as factors influencing reproductive health-promoting behaviors. According to the regression model, the explanatory power of factors affecting reproductive health-promoting behaviors among married women was 51.2%. Conclusion A history of reproductive diseases, family values, and reproductive health knowledge were identified as factors influencing reproductive health-promoting behaviors. These results provide basic data for the development of a reproductive health-promoting program, including a positive approach to reproductive health among married women, and can serve as a basis for further research on intervention strategies

Factors Influencing Posttraumatic Growth of Gynecologic Oncology Patients Undergoing Chemotherapy

PURPOSE: The purpose of this study was to investigate the factors impacting the posttraumatic growth (PTG) factors during chemotherapy in gynecologic oncology patients. METHOD: The data were collected at six hospitals at a university hospital, general hospital, women&apos;s hospital, and 3 oncology hospitals in D metropolitan city. The participants of the study were 135 female patients undergoing chemotherapy for their gynecologic oncology. To identify the factors that influence PTG, we used the questionnaires for the family support, sexual distress, health promoting behavior, and PTG. RESULTS: There was a significant positive correlation between family support and health promoting behavior and PTG. There was significant negative correlation between sexual distress and PTG. Factors impacting the PTG of gynecologic oncology women undergoing chemotherapy were age, recurrence, family support, sexual distress, and health promoting behavior. These factors accounted for 47.0% of PTG. CONCLUSION: It is necessary to develop and apply programs that include sexual distress management education, and health promotion with families. PTG programs for gynecologic oncology patients undergoing chemotherapy should be approached considering these results

Appraising the Potential Uses and Harms of LLMs for Medical Systematic Reviews

Medical systematic reviews play a vital role in healthcare decision making and policy. However, their production is time-consuming, limiting the availability of high-quality and up-to-date evidence summaries. Recent advancements in large language models (LLMs) offer the potential to automatically generate literature reviews on demand, addressing this issue. However, LLMs sometimes generate inaccurate (and potentially misleading) texts by hallucination or omission. In healthcare, this can make LLMs unusable at best and dangerous at worst. We conducted 16 interviews with international systematic review experts to characterize the perceived utility and risks of LLMs in the specific context of medical evidence reviews. Experts indicated that LLMs can assist in the writing process by drafting summaries, generating templates, distilling information, and crosschecking information. They also raised concerns regarding confidently composed but inaccurate LLM outputs and other potential downstream harms, including decreased accountability and proliferation of low-quality reviews. Informed by this qualitative analysis, we identify criteria for rigorous evaluation of biomedical LLMs aligned with domain expert views.Comment: 18 pages, 2 figures, 8 tables. Accepted as an EMNLP 2023 main pape

Structural abnormalities in benign childhood epilepsy with centrotemporal spikes (BCECTS)

AbstractPurposeThe aim of this study was to investigate cortical thickness and gray matter volume abnormalities in benign childhood epilepsy with centrotemporal spikes (BCECTS). We additionally assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities.MethodsSurface and volumetric MR imaging data of children with newly diagnosed BCECTS (n=20, 14 males) and age-matched healthy controls (n=20) were analyzed using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu). An additional comparison was performed between BCECTS children with and without ADHD (each, n=8). A group comparison was carried out using an analysis of covariance with a value of significance set as p<0.01 or p<0.05.ResultsChildren with BCECTS had significantly thicker right superior frontal, superior temporal, middle temporal, and left pars triangularis cortices. Voxel-based morphometric analysis revealed significantly larger cortical gray matter volumes of the right precuneus, left orbitofrontal, pars orbitalis, precentral gyri, and bilateral putamen and the amygdala of children with BCECTS compared to healthy controls. BCECTS patients with ADHD had significantly thicker left caudal anterior and posterior cingulate gyri and a significantly larger left pars opercularis gyral volume compared to BCECTS patients without ADHD.ConclusionChildren with BCECTS have thicker or larger gray matters in the corticostriatal circuitry at the onset of epilepsy. Comorbid ADHD is also associated with structural aberrations. These findings suggest structural disruptions of the brain network are associated with specific developmental electro-clinical syndromes

Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life

A preterm female infant born at 27 weeks of gestation with a birth weight of 990 g developed acute hypotonia, apnea, hypotension and bradycardia mimicking septic shock syndrome at 14h after birth. Laboratory tests indicated a severe hypermagnesemia of 45 mg/dL. The renal function, complete blood count and maternal blood concentrations of magnesium were normal, and the blood cultures were negative. The patient recovered with treatment including exchange transfusion. However, the etiology of the severe hypermagnesemia remains unknown

Disruption of the astrocyte–neuron interaction is responsible for the impairments in learning and memory in 5XFAD mice: an Alzheimers disease animal model

The morphological dynamics of astrocytes are altered in the hippocampus during memory induction. Astrocyte–neuron interactions on synapses are called tripartite synapses. These control the synaptic function in the central nervous system. Astrocytes are activated in a reactive state by STAT3 phosphorylation in 5XFAD mice, an Alzheimers disease (AD) animal model. However, changes in astrocyte–neuron interactions in reactive or resting-state astrocytes during memory induction remain to be defined. Here, we investigated the time-dependent changes in astrocyte morphology and the number of astrocyte–neuron interactions in the hippocampus over the course of long-term memory formation in 5XFAD mice. Hippocampal-dependent long-term memory was induced using a contextual fear conditioning test in 5XFAD mice. The number of astrocytic processes increased in both wild-type and 5XFAD mice during memory formation. To assess astrocyte–neuron interactions in the hippocampal dentate gyrus, we counted the colocalization of glial fibrillary acidic protein and postsynaptic density protein 95 via immunofluorescence. Both groups revealed an increase in astrocyte–neuron interactions after memory induction. At 24 h after memory formation, the number of tripartite synapses returned to baseline levels in both groups. However, the total number of astrocyte–neuron interactions was significantly decreased in 5XFAD mice. Administration of Stattic, a STAT3 phosphorylation inhibitor, rescued the number of astrocyte–neuron interactions in 5XFAD mice. In conclusion, we suggest that a decreased number of astrocyte–neuron interactions may underlie memory impairment in the early stages of AD.This research was supported by the Korea Brain Research Institute (KBRI) basic research program through Korea Brain Research Institute funded by the Ministry of Science, ICT (21-BR-02-13, 21-BR-03-02 to Y.H.J.) and by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Sci‑ence and Technology (NRF-2020R1A2C1011839 awarded to H.S.K.)