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Ganglioside-induced differentiation associated protein 1 (GDAP1) gene encodes a protein of the mitochondrial outer membrane and of the mitochondrial membrane contacts with the endoplasmic reticulum (MAMs) and lysosomes. Since mutations in GDAP1 cause Charcot-Marie-Tooth, an inherited motor and sensory neuropathy, its function is essential for peripheral nerve physiology. Our previous studies showed structural and functional defects in mitochondria and their contacts when GDAP1 is depleted. Nevertheless, the underlying axonal pathophysiological events remain unclear. Here, we have used embryonic motor neurons (eMNs) cultures from Gdap1 knockout (Gdap1-/-) mice to investigate in vivo mitochondria and calcium homeostasis in the axons. We imaged mitochondrial axonal transport and we found a defective pattern in the Gdap1-/- eMNs. We also detected pathological and functional mitochondria membrane abnormalities with a drop in ATP production and a deteriorated bioenergetic status. Another consequence of the loss of GDAP1 in the soma and axons of eMNs was the in vivo increase calcium levels in both basal conditions and during recovery after neuronal stimulation with glutamate. Further, we found that glutamate-stimulation of respiration was lower in Gdap1-/- eMNs showing that the basal bioenergetics failure jeopardizes a full respiratory response and prevents a rapid return of calcium to basal levels. Together, our results demonstrate that the loss of GDAP1 critically compromises the morphology and function of mitochondria and its relationship with calcium homeostasis in the soma and axons, offering important insight into the cellular mechanisms associated with axonal degeneration of GDAP1-related CMT neuropathies and the relevance that axon length may have.
The COVID-19 pandemic has brought unprecedented changes to young adults' lives, resulting in mental health difficulties for many; however, some individuals are particularly prone to heightened anxiety. Little is known about the early life predictors of anxiety during the pandemic. We examined a developmental pathway from behavioral inhibition (BI), a temperament characterized by fearful responses toward novelty, to changes in young adults' anxiety during the initial period of the pandemic. We hypothesized that a stable pattern of BI across early childhood would predict greater adolescent worry dysregulation, which in turn would predict increases in young adult anxiety during a stressful phase of the pandemic.
Participants (N= 291; 54% female) were followed from toddlerhood to young adulthood. BI was observed at ages 2 and 3 years. Social wariness was observed at age 7 years. Participants rated their worry dysregulation in adolescence (age 15) and anxiety in young adulthood (age 18) at 2 assessments during the COVID-19 pandemic, 1 month apart.
A significant moderated mediation, in which a stable pattern of BI from toddlerhood to childhood, as compared to the absence of this pattern, predicted greater worry dysregulation in adolescence. Worry dysregulation predicted elevated young adult anxiety in the second assessment during COVID-19, even after accounting for the first assessment.
This study identifies a developmental pathway from toddlerhood BI to young adults' elevated anxiety during the COVID-19 pandemic. check details Findings have implications for early identification of individuals at risk for dysregulated worry and the prevention of anxiety during stressful life events in young adulthood.
This study identifies a developmental pathway from toddlerhood BI to young adults' elevated anxiety during the COVID-19 pandemic. Findings have implications for early identification of individuals at risk for dysregulated worry and the prevention of anxiety during stressful life events in young adulthood.
The National Cancer Center has provided nationwide endoscope reprocessing training to hospitals annually performing national gastric and colorectal cancer screening in Korea since 2012. This study aimed to evaluate the adherence of past participants of endoscope reprocessing training to the reprocessing guidelines and their satisfaction with the current training.
Training on endoscope reprocessing was implemented 18 times across the country, from June 2019 to November 2019. Immediately after the training, participants filled a paper questionnaire related to reprocessing practices and satisfaction with the current training anonymously.
A total of 1,132 participants trained responded to the survey (response rate, 95.4%). Of the study participants, 45.7% participated in the past endoscope reprocessing training, and 94.6% of them answered that they have adhered to the endoscope reprocessing guidelines. Experience of participation in endoscope reprocessing training was significantly associated with practical adherence to endoscope reprocessing guidelines (aOR, 6.55; 95% CI, 3.93 to 10.91). And, 91% of study participants were satisfied with the current endoscope reprocessing training.
The current training on endoscope reprocessing provided at the national level could help ensure adherence to reprocessing guidelines, resulting in obtaining quality control for endoscopy. However, about half of practitioners currently working in endoscopy units had not received sufficient reprocessing training, and thus more training is needed for them.
The current training on endoscope reprocessing provided at the national level could help ensure adherence to reprocessing guidelines, resulting in obtaining quality control for endoscopy. However, about half of practitioners currently working in endoscopy units had not received sufficient reprocessing training, and thus more training is needed for them.Because of the abuse of antibiotics, clinical strains began to become more drug-resistant. Their evolution has long surpassed the speed of us looking for a new generation of antibacterial drugs. Therefore, it is urgent to discover a new antimicrobial substance to alleviate the pressure on conventional antibiotics. Antimicrobial peptides (AMP) are known for their significant activity towards a broad spectrum of bacteria, protozoa, yeasts, filamentous fungi. Here, we report a novel AMP named Dermaseptin-TO. Results demonstrate that Dermaseptin-TO can quickly exhibit antimicrobial activity to bacteria and yeast in a dose-related way. The highest minimum inhibit concentration (MIC) was observed in the E.faecalis group (128 μM). Also, haemolytic outcomes showed no more than 10.65% of red blood cells were affected when in the same concentrations or below. Besides, Dermaseptin-TO also showed anticancer activity at a higher concentration. From the above, evidence proved that Phyllomedusine frog skin secretion is still a rich source that contains novel AMP and Dermaseptin-TO is competent to become an antimicrobial agent, its anticancer activity may broaden the way in basic cancer research.
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