Objective: This case report describes a novel use of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in a patient whose glycogen storage disease (GSD) was unmasked by statin therapy. Evidence-based guidelines for the management of hyperlipidemia in patients with concurrent neuromuscular disorders (NMD) remain limited. Methods: We report the case of a 46-year-old man with hyperlipidemia, treated with simvastatin, who presented with 2 days of thigh pain without weakness or dark urine. He was diagnosed with statin-associated muscle symptoms. On further interview, the patient recalled experiencing thigh muscle soreness decades earlier while in the military, at which time his creatine phosphokinase (CPK) ranged between 1,200 and 3,000 U/L. He admitted not disclosing this history or a prior muscle biopsy. Results: Muscle biopsy and electromyographyerve conduction velocity studies were followed by whole-exome sequencing, which demonstrated hemizygosity for c.2369+1 G>T, a pathogenic variant in the PHKA1 gene, consistent with GSD IXd. He was subsequently treated with 2 PCSK9 inhibitors (first evolocumab, then alirocumab). A comprehensive literature review identified only 2 previously reported cases of GSD treated with alirocumab. Conclusion Even if not volunteered, a history of muscle symptoms should be actively sought before initiating statins, with baseline CPK measurement if indicated. As statins are increasingly prescribed, additional cases of GSD may be unmasked, underscoring the need to define optimal therapy for hyperlipidemia in NMD, including GSD. We propose a specific role for PCSK9 inhibitors in patients with statin intolerance and GSD IXd, which has not been previously reported.

BACKGROUND: Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential. METHODS: Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays. RESULTS: Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs. CONCLUSIONS These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.

Purpose: Central venous catheter (CVC) insertion is a fundamental skill required for trainees to become proficient. Simulation-based training (SBT) has been shown to improve trainees’ CVC insertion performance effectively. However, implementing a CVC curriculum requires substantial costs and resources. Currently, there is a lack of validated CVC curricula that institutions can adopt as frameworks. This study aimed to evaluate the effectiveness of our institution’s CVC simulation curriculum in improving residents’ confidence and comfort with CVC insertion and management. Materials and Methods: First-year residents (n=118) participated in SBT between 2017 and 2023. Among them, 57 (48%) participants completed surveys before training and 6 months post-training to assess changes in comfort levels across various aspects of CVC insertion. Survey responses were analyzed to evaluate the overall changes in comfort by year and items. Results: Overall comfort increased from 42.1% before training to 81.3% after training (P<0.01), with notable improvements in nonprocedural aspects. Comfort with performing the unsupervised procedure increased by 16.7% (P<0.05) but remained low post-training (29.6%). Conclusion These findings suggest that the curriculum effectively enhances residents’ comfort, particularly in nonprocedural aspects, but only partially prepares them for unsupervised CVC insertions. This indicates a gap in procedural skill acquisition despite the overall positive trends. Implementing a similar CVC curriculum may help institutions reduce CVC insertion-associated complications.

BACKGROUND: Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential. METHODS: Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays. RESULTS: Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs. CONCLUSIONS These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.

Purpose: Central venous catheter (CVC) insertion is a fundamental skill required for trainees to become proficient. Simulation-based training (SBT) has been shown to improve trainees’ CVC insertion performance effectively. However, implementing a CVC curriculum requires substantial costs and resources. Currently, there is a lack of validated CVC curricula that institutions can adopt as frameworks. This study aimed to evaluate the effectiveness of our institution’s CVC simulation curriculum in improving residents’ confidence and comfort with CVC insertion and management. Materials and Methods: First-year residents (n=118) participated in SBT between 2017 and 2023. Among them, 57 (48%) participants completed surveys before training and 6 months post-training to assess changes in comfort levels across various aspects of CVC insertion. Survey responses were analyzed to evaluate the overall changes in comfort by year and items. Results: Overall comfort increased from 42.1% before training to 81.3% after training (P<0.01), with notable improvements in nonprocedural aspects. Comfort with performing the unsupervised procedure increased by 16.7% (P<0.05) but remained low post-training (29.6%). Conclusion These findings suggest that the curriculum effectively enhances residents’ comfort, particularly in nonprocedural aspects, but only partially prepares them for unsupervised CVC insertions. This indicates a gap in procedural skill acquisition despite the overall positive trends. Implementing a similar CVC curriculum may help institutions reduce CVC insertion-associated complications.

BACKGROUND: Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential. METHODS: Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays. RESULTS: Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs. CONCLUSIONS These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.

Purpose: Central venous catheter (CVC) insertion is a fundamental skill required for trainees to become proficient. Simulation-based training (SBT) has been shown to improve trainees’ CVC insertion performance effectively. However, implementing a CVC curriculum requires substantial costs and resources. Currently, there is a lack of validated CVC curricula that institutions can adopt as frameworks. This study aimed to evaluate the effectiveness of our institution’s CVC simulation curriculum in improving residents’ confidence and comfort with CVC insertion and management. Materials and Methods: First-year residents (n=118) participated in SBT between 2017 and 2023. Among them, 57 (48%) participants completed surveys before training and 6 months post-training to assess changes in comfort levels across various aspects of CVC insertion. Survey responses were analyzed to evaluate the overall changes in comfort by year and items. Results: Overall comfort increased from 42.1% before training to 81.3% after training (P<0.01), with notable improvements in nonprocedural aspects. Comfort with performing the unsupervised procedure increased by 16.7% (P<0.05) but remained low post-training (29.6%). Conclusion These findings suggest that the curriculum effectively enhances residents’ comfort, particularly in nonprocedural aspects, but only partially prepares them for unsupervised CVC insertions. This indicates a gap in procedural skill acquisition despite the overall positive trends. Implementing a similar CVC curriculum may help institutions reduce CVC insertion-associated complications.

BACKGROUND: Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential. METHODS: Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays. RESULTS: Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs. CONCLUSIONS These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.

Purpose: Central venous catheter (CVC) insertion is a fundamental skill required for trainees to become proficient. Simulation-based training (SBT) has been shown to improve trainees’ CVC insertion performance effectively. However, implementing a CVC curriculum requires substantial costs and resources. Currently, there is a lack of validated CVC curricula that institutions can adopt as frameworks. This study aimed to evaluate the effectiveness of our institution’s CVC simulation curriculum in improving residents’ confidence and comfort with CVC insertion and management. Materials and Methods: First-year residents (n=118) participated in SBT between 2017 and 2023. Among them, 57 (48%) participants completed surveys before training and 6 months post-training to assess changes in comfort levels across various aspects of CVC insertion. Survey responses were analyzed to evaluate the overall changes in comfort by year and items. Results: Overall comfort increased from 42.1% before training to 81.3% after training (P<0.01), with notable improvements in nonprocedural aspects. Comfort with performing the unsupervised procedure increased by 16.7% (P<0.05) but remained low post-training (29.6%). Conclusion These findings suggest that the curriculum effectively enhances residents’ comfort, particularly in nonprocedural aspects, but only partially prepares them for unsupervised CVC insertions. This indicates a gap in procedural skill acquisition despite the overall positive trends. Implementing a similar CVC curriculum may help institutions reduce CVC insertion-associated complications.

BACKGROUND: Priming strategies that improve the functionality of MSCs may be required to address issues limiting successful clinical translation of MSC therapies. For conditions requiring high trophic support such as brain and spinal cord injuries, priming MSCs to produce higher levels of trophic factors may be instrumental to facilitate translation of current MSC therapies. We developed and tested a novel molecular priming paradigm using docosahexaenoic acid (DHA) to prime adipose tissue-derived mesenchymal stromal cells (ASCs) to enhance the secretome neuroregulatory potential. METHODS: Comprehensive dose–response and time-course assays were carried to determine an optimal priming protocol. Secretome total protein measurements were taken in association with cell viability, density and morphometric assessments. Cell identity and differentiation capacity were studied by flow cytometry and lineage-specific markers. Cell growth was assessed by trypan-blue exclusion and senescence was probed over time using SA-b-gal, morphometry and gene expression. Secretomes were tested for their ability to support differentiation and neurite outgrowth of human neural progenitor cells (hNPCs). Neuroregulatory proteins in the secretome were identified using multiplex membrane arrays. RESULTS: Priming with 40 lM DHA for 72 h significantly enhanced the biosynthetic capacity of ASCs, producing a secretome with higher protein levels and increased metabolic viability. DHA priming enhanced ASCs adipogenic differentiation and adapted their responses to replicative senescence induction. Furthermore, priming increased concentrations of neurotrophic factors in the secretome promoting neurite outgrowth and modulating the differentiation of hNPCs. CONCLUSIONS These results provide proof-of-concept evidence that DHA priming is a viable strategy to improve the neuroregulatory profile of ASCs.