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Mutations in skeletal muscle α-actin (Acta1) cause myopathies. In a mouse model of congenital myopathy, heterozygous Acta1 (H40Y) knock-in (Acta1+/Ki) mice exhibit features of human nemaline myopathy, including premature lethality, severe muscle weakness, reduced mobility, and the presence of nemaline rods in muscle fibers. In this study, we investigated the impact of Acta1 (H40Y) mutation on the neuromuscular junction (NMJ). We found that the NMJs were markedly fragmented in Acta1+/Ki mice. Electrophysiological analysis revealed a decrease in amplitude but increase in frequency of miniature end-plate potential (mEPP) at the NMJs in Acta1+/Ki mice, compared with those in wild type (Acta1+/+) mice. Evoked end-plate potential (EPP) remained similar at the NMJs in Acta1+/Ki and Acta1+/+ mice, but quantal content was increased at the NMJs in Acta1+/Ki, compared with Acta1+/+ mice, suggesting a homeostatic compensation at the NMJs in Acta1+/Ki mice to maintain normal levels of neurotransmitter release. Furthermore, short-term synaptic plasticity of the NMJs was compromised in Acta1+/Ki mice. Together, these results demonstrate that skeletal Acta1 H40Y mutation, albeit muscle-origin, leads to both morphological and functional defects at the NMJ.
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Enfermedades Musculares , Miopatías Nemalínicas , Miotonía Congénita , Humanos , Ratones , Animales , Actinas/genética , Músculo Esquelético/fisiología , Miopatías Nemalínicas/genética , Unión Neuromuscular/genética , Modelos Animales de Enfermedad , MutaciónRESUMEN
MuSK is a receptor tyrosine kinase (RTK) that plays essential roles in the formation and maintenance of the neuromuscular junction. Distinct from most members of RTK family, MuSK activation requires not only its cognate ligand agrin but also its coreceptors LRP4. However, how agrin and LRP4 coactivate MuSK remains unclear. Here, we report the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK in a stoichiometry of 1:1:1. This structure reveals that arc-shaped LRP4 simultaneously recruits both agrin and MuSK to its central cavity, thereby promoting a direct interaction between agrin and MuSK. Our cryo-EM analyses therefore uncover the assembly mechanism of agrin/LRP4/MuSK signaling complex and reveal how MuSK receptor is activated by concurrent binding of agrin and LRP4.
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Agrina , Receptores Colinérgicos , Receptores Colinérgicos/metabolismo , Agrina/química , Agrina/metabolismo , Proteínas Relacionadas con Receptor de LDL/química , Transducción de Señal , Unión Neuromuscular/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
PURPOSE: To assess the survival impact of pre-concurrent chemoradiotherapy (CCRT) staging with positron emission tomography-CT (PET-CT) in patients with unresectable epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. METHODS: Patients with unresectable stage IIIA-IIIC EGFR mutation-positive adenocarcinoma undergoing definitive CCRT were divided into two groups: those who received PET-CT staging prior to CCRT and those with other staging methods. Survival outcomes were compared after propensity score matching. RESULTS: Analysis of 11 856 patients (5928 in each group) showed that PET-CT staging was associated with improved survival (adjusted HR of all-cause mortality: 0.74, 95% CI 0.71 to 0.79). Other prognostic factors included male sex, age group, clinical stage, adjuvant treatment, smoking status, Charlson Comorbidity Index score and treatment setting. CONCLUSION: Pre-CCRT staging with PET-CT in patients with unresectable EGFR mutation-positive adenocarcinoma of clinical stage IIIA-IIIC was associated with enhanced survival. Independent prognostic factors were also identified.
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In recent years, organic-inorganic hybrid perovskite materials have become one of the most promising materials in the new generation of solar cells. These perovskites can provide excellent photoelectric properties after a simple fabrication process. Although perovskite solar cells have achieved high power conversion efficiency, instability concerns regarding material exposure to heat, moisture, air, and UV light present hindrances to commercialization. In this study, three kinds of perovskites (MAPbI3, MAPbI3-xBrx, and MAPbI3-xClx) were used to investigate the crystal stability upon exposure to heat and UV light. SEM, XRD, and FTIR were used to observe the surface morphology, crystal structure, and functional groups of the perovskite thin films. XPS was used to examine the surface composition and chemical state of the perovskite thin films under different conditions. Among these three types of perovskites, it was found that the MAPbI3-xBrx crystal demonstrated the best stability. ToF-SIMS was used to confirm the molecular distribution of the MAPbI3-xBrx films upon exposure to heat and UV light at different depths. ToF-SIMS revealed that [Pb]+ and [PbI]+ aggregated at the interface between the perovskite and ITO substrate after 14 days of thermal treatment. On the other hand, [Pb]+ and [PbI]+ were distributed uniformly after 3 days of UV exposure. This study systematically analyzed and revealed the thermal- and UV-induced degradation process of three perovskite films by using surface analysis techniques. It was concluded that bromine-doped perovskite films had better stability, and UV light caused more severe damage than heat.
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INTRODUCTION AND OBJECTIVES: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. PATIENTS AND METHODS: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017-2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999-2016) to assess the correlation with mortality. RESULTS: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. CONCLUSIONS: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.
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Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Masculino , Cirrosis Hepática/patología , Cirrosis Hepática/diagnóstico , Persona de Mediana Edad , Adulto , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Biopsia , Índice de Severidad de la Enfermedad , Medición de Riesgo , Encuestas Nutricionales , Tamizaje Masivo/métodos , Valor Predictivo de las Pruebas , Anciano , Hígado/patología , Hígado/diagnóstico por imagenRESUMEN
BACKGROUND: Children with dental caries are treated with stainless steel metal crowns (SSC), but the aesthetics and precision still need to be improved. Currently, both 3D-printed resin crowns (PRC) and computer-aided design/computer-aided manufacture (CAD/CAM) resin crowns (CRC) meet the clinical requirements for crown applications in terms of strength, production time, cost, and aesthetics. AIM: This study replaced SSC with customized resin crowns by 3D printing and CAD/CAM. DESIGN: In this study, PRC, CRC, and SSC were used for incisor and molar restorations, and 60 crowns were made with 10 for each group. The fabrication efficiency, surface characteristics, marginal fit, and stability of the two different crowns were evaluated. RESULTS: PRC and CRC show superior color and surface characteristics, though production times are longer (5.3-12.4 times and 3.3-9.1 times, respectively) than for SSC (p < .05). They, however, can be completed within 80 min. Edge gaps for PRC and CRC are significantly lower (13.0-19.2 times and 13.0-13.7 times) than for SSC (p < .05). All materials exhibit good stability. CONCLUSION: The 3D-PRCs and CAD/CAM resin crowns may replace SSCs as a potential choice for clinical child caries.
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PURPOSE: To evaluate the effects of two base types and three restoration designs on the resin consumption and trueness of the 3D-printed dental casts. Additionally, the study explored the dimensional stability of these 3D-printed dental casts after 1 year of storage. MATERIALS AND METHODS: Various types of reference dental casts were specifically designed to represent three types of dental restoration fabrications, including full-arch (FA), long-span (LS), and single-unit (SU) prostheses. The reference casts were digitized with a dental laboratory scanner and used to create flat and hollow base designs (N = 18) for the 3D-printed study casts. The 3D-printed study casts were digitized and evaluated against their corresponding references immediately after 3D printing and again after 1 year of storage, with the trueness quantified using the root mean square error (RMSE) at both time points. Volumes of resin used were recorded to measure resin consumption, and the weights of the 3D-printed study casts were also measured. The data were analyzed using two-way ANOVA and a Tukey post hoc test, α = 0.05. RESULTS: Volumetric analysis showed the flat-base design had significantly higher resin consumption with weights for the FA group at 42.51 ± 0.16 g, the LS group at 31.64 ± 0.07 g, and the SU group at 27.67 ± 0.31 g, as opposed to 26.22 ± 1.01 g, 22.86 ± 0.93 g, and 20.10 ± 0.19 g for the hollow designs respectively (p < 0.001). Trueness, assessed through two-way ANOVA, revealed that the flat-base design had lower RMSE values indicating better trueness in the LS (54 ± 6 µm) and SU (59 ± 7 µm) groups compared to the hollow-base design (LS: 73 ± 5, SU: 99 ± 11 µm, both p < 0.001), with no significant difference in the FA group (flat-base: 50 ± 3, hollow: 47 ± 5 µm, p = 0.398). After 1 year, the flat-base design demonstrated superior dimensional stability in the LS (flat base: 56 ± 6 µm, hollow base: 149 ±45 µm, p < 0.001) and SU groups (flat base: 95 ± 8 µm, hollow base: 183 ±27 µm, p < 0.001), with the FA group showing no significant difference in the base design (flat base: 47 ± 9, hollow base: 62 ± 12 µm, p = 0.428). CONCLUSIONS: The hollow-base design group showed lower resin consumption than the flat-base design group. However, the flat-base designs exhibited superior trueness and less distortion after 1 year of storage. These findings indicate that despite the higher material usage, flat-base designs provide better initial accuracy and maintain their dimensional stability over time for most groups.
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BACKGROUND: In patients with nonalcoholic fatty liver disease, liver fibrosis was associated with a higher risk of cardiovascular events. However, the relationship between liver fibrosis scores and clinical outcomes in patients with cardiovascular disease remains unclear. METHODS: Searching from PubMed, EMBASE and Cochrane Library databases yielded cohort studies that reported adjusted effect size between liver fibrosis scores (Fibrosis-4 score [FIB-4] or NAFLD fibrosis score [NFS]) and prognosis in patients with cardiovascular disease. The effect size was computed using a random-effects model. RESULTS: This meta-analysis included twelve cohort studies involving 25,252 patients with cardiovascular disease. Participants with the highest baseline level of FIB-4 or NFS had a significantly increased risk of cardiovascular events (FIB-4, HR: 1.75, 95% CI: 1.53-2.00, I 2 = 0%; NFS, HR: 1.92, 95% CI: 1.50-2.47, I 2 = 47%). This finding was consistent with the analysis of FIB-4 or NFS as a continuous variable (per 1-unit increment FIB-4, HR: 1.15, 95% CI: 1.06-1.24, I 2 = 72%; NFS, HR: 1.15, 95% CI: 1.07-1.24, I 2 = 71%). Furthermore, participants with the highest levels of FIB-4 or NFS had a greater risk of cardiovascular mortality (FIB-4, HR: 2.07, 95% CI: 1.19-3.61, I 2 = 89%; NFS, HR: 3.72, 95% CI: 2.62-5.29, I 2 = 60%) and all-cause mortality (FIB-4, HR: 1.81, 95% CI: 1.24-2.66, I 2 = 90%; NFS, HR: 3.49, 95% CI: 2.82-4.31, I 2 = 25%). This result was also consistent as a continuous variable. CONCLUSION: Higher levels of FIB-4 and NFS are related to an increased risk of cardiovascular events, cardiovascular mortality and all-cause mortality in patients with cardiovascular disease.
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Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Aspartato Aminotransferasas , Biopsia/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Humanos , Cirrosis Hepática/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Conversion of potable reuse water utilities and drinking water utilities from a low-pressure UV/H2O2 (LPUV/H2O2) advanced oxidation process (AOP) to alternative AOPs in which oxidants can effectively absorb photons and rapidly generate radicals has attracted great interest. Herein, we propose a novel UVA/ClO2 AOP for different water treatment scenarios because of reduced photon absorption by the background matrix and high molar absorptivity for ClO2 at UVA wavelengths. While the photolysis of ClO2 produces â¢Cl + O2 or â¢ClO + O(3P) via distinct product channels, we determined the parameters needed to accurately model the loss of oxidants and the formation of byproducts and combined a kinetic model with experimental data to determine quantum yields (Φ). Modeling incorporating the optimized Φ simultaneously predicted oxidant loss and the formation of major products -HOCl, Cl-, and ClO3-. We also systematically investigated the removal of three contaminants exhibiting different radical reactivities, the formation of 35 regulated and unregulated halogenated disinfection byproducts (DBPs), DBP-associated toxicity, and N-acetylcysteine thiol reactivity in synthetic or authentic RO permeates/surface waters treated by different AOPs. The kinetic model developed in this study was used to optimize operating conditions to control undesired products and improve contaminant removal efficiency. The results indicate that UVA/ClO2 can outperform LPUV/H2O2 in terms of electrical energy per order of contaminant degradation, disinfection byproduct formation, and toxicity indices.
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Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Cloro , Compuestos de Cloro , Desinfección , Peróxido de Hidrógeno , Oxidantes , Oxidación-Reducción , Óxidos , Fotólisis , Rayos Ultravioleta , Contaminantes Químicos del Agua/análisisRESUMEN
PURPOSE: Clinicians face personal barriers that impede the provision of bereavement care and require education in hospice care. This study aims to investigate the effects of an educational bereavement program on emotional and cognitive barriers, self-efficacy, and professional quality of life among clinicians in hospice care. METHODS: A pretest-posttest design was implemented. A total of 194 clinicians with working experience in hospice care were recruited. The participants underwent a 12-h workshop. The content included lectures, role-play, and group discussion. Emotional and cognitive barriers, self-efficacy, and professional quality of life were measured before and after the program and at 3-month follow-up. RESULTS: After the educational program, negative emotional barriers (F (2, 386) = 17.07, p < 0.001), lack of ability (F (2, 386) = 20.11, p < 0.001), belief in avoidance (F (2, 386) = 7.10, p = 0.001), outcome expectancy (F (2, 386) = 11.32, p < 0.001), and burnout (F (2, 386) = 5.59, p = 0.005) decreased significantly. Self-efficacy (F (2, 386) = 5.37, p = 0.006) and compassion satisfaction (F (2, 386) = 127.99, p < 0.001) increased significantly. CONCLUSION: The educational program addressed personal barriers to bereavement care. Role-play and group discussion about emotional and cognitive barriers can reduce barriers and improve self-efficacy in clinicians in hospice care.
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Aflicción , Cuidados Paliativos al Final de la Vida , Pesar , Humanos , Calidad de Vida , AutoeficaciaRESUMEN
OBJECTIVES: Professional quality of life involves the negative and positive effects of proving care to terminal patients on health care professionals, including burnout and compassion satisfaction. Around 18% of hospice staff have experienced burnout, and few studies explore the role of an innate ability to cope with burnout. The aim of this study was to explore the significant predictors of burnout and compassion satisfaction as well as the coping strategies among hospice staff in Taiwan. METHODS: A cross-sectional study was conducted, and 220 hospice staff were recruited. Standardized questionnaires were used to collect self-rated stress and growth due to hospice care, self-efficacy, self-awareness, and managing emotion. RESULTS: Hospice staff who perceived higher stress and lower growth due to hospice care and had lower self-efficacy in providing hospice care experienced higher burnout and lower compassion satisfaction. Those who had a lower level of ability related to self-awareness and managing emotion tended to experience higher burnout. The common coping strategies included seeking social support, taking professional courses for clinical skills, and developing hobbies. CONCLUSION: Hospice staff have to develop professional abilities in regard to hospice care as well as an ability to maintain awareness and manage emotions related to work.
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Agotamiento Profesional , Desgaste por Empatía , Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Desgaste por Empatía/psicología , Estudios Transversales , Empatía , Humanos , Satisfacción Personal , Calidad de Vida , Autoeficacia , Encuestas y Cuestionarios , TaiwánRESUMEN
Schwann cells are integral components of vertebrate neuromuscular synapses; in their absence, pre-synaptic nerve terminals withdraw from post-synaptic muscles, leading to muscle denervation and synapse loss at the developing neuromuscular junction (NMJ). Here, we report a rescue of muscle denervation and neuromuscular synapses loss in type III Neuregulin 1 mutant mice (CRD-Nrg1-/-), which lack Schwann cells. We found that muscle denervation and neuromuscular synapse loss were prevented in CRD-Nrg1-/-mice when presynaptic activity was blocked by ablating a specific gene, such as Snap25 (synaptosomal-associated 25 kDa protein) or Chat (choline acetyltransferase). Further, these effects were mediated by a pathway that requires postsynaptic acetylcholine receptors (AChRs), because ablating Chrna1 (acetylcholine receptor α1 subunit), which encodes muscle-specific AChRs in CRD-Nrg1-/-mice also rescued muscle denervation. Moreover, genetically ablating muscle dihydropyridine receptor (DHPR) ß1 subunit (Cacnb1) or ryanodine receptor 1 (Ryr1) also rescued muscle denervation and neuromuscular synapse loss in CRD-Nrg1-/-mice. Thus, these genetic manipulations follow a pathway-from presynaptic to postsynaptic, and, ultimately to muscle activity mediated by DHPRs and Ryr1. Importantly, electrophysiological analyses reveal robust synaptic activity in the rescued, Schwann-cell deficient NMJs in CRD-Nrg1-/-Cacnb1-/-or CRD-Nrg1-/-Ryr1-/-mutant mice. Thus, a blockade of synaptic activity, although sufficient, is not necessary to preserve NMJs that lack Schwann cells. Instead, a blockade of muscle activity mediated by DHRPs and Ryr1 is both necessary and sufficient for preserving NMJs that lack Schwann cells. These findings suggest that muscle activity mediated by DHPRs/Ryr1 may destabilize developing NMJs and that Schwann cells play crucial roles in counteracting such a destabilizing activity to preserve neuromuscular synapses during development.
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Canales de Calcio Tipo L/genética , Neurregulina-1/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Sinapsis/genética , Animales , Axones/metabolismo , Electrofisiología , Humanos , Ratones , Neuronas Motoras/metabolismo , Desnervación Muscular , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Regeneración Nerviosa/genética , Unión Neuromuscular/genética , Terminales Presinápticos/metabolismo , Receptores Nicotínicos/genética , Células de Schwann/metabolismo , Sinapsis/fisiología , Proteína 25 Asociada a Sinaptosomas/genéticaRESUMEN
Glial cells regulate multiple aspects of synaptogenesis. In the absence of Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using a genetic approach, we show that neural activity-regulated negative factors produced by muscle drive neurodegeneration in Schwann cell-deficient mice. We find that thrombin, the hepatic serine protease central to the hemostatic coagulation cascade, is one such negative factor. Trancriptomic analysis shows that expression of the antithrombins serpin C1 and D1 is significantly reduced in Schwann cell-deficient mice. In the absence of peripheral neuromuscular activity, neurodegeneration is completely blocked, and expression of prothrombin in muscle is markedly reduced. In the absence of muscle-derived prothrombin, neurodegeneration is also markedly reduced. Together, these results suggest that Schwann cells regulate NMJs by opposing the effects of activity-regulated, muscle-derived negative factors and provide the first genetic evidence that thrombin plays a central role outside of the coagulation system.
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Antitrombina III/genética , Cofactor II de Heparina/genética , Unión Neuromuscular/genética , Protrombina/genética , Sinapsis/genética , Animales , Perfilación de la Expresión Génica , Ratones , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Músculo Esquelético/metabolismo , Degeneración Nerviosa/genética , Neuroglía , Unión Neuromuscular/crecimiento & desarrollo , Células de Schwann/metabolismo , Trombina/genéticaRESUMEN
Synaptic transmission occurs when an action potential triggers neurotransmitter release via the fusion of synaptic vesicles with the presynaptic membrane, driven by the formation of SNARE complexes composed of the vesicular (v)-SNARE synaptobrevin and the target (t)-SNAREs Snap-25 and syntaxin-1. Neurotransmitters are also released spontaneously, independent of an action potential, through the fusion of synaptic vesicles with the presynaptic membrane. The major neuronal vSNAREs, synaptobrevin-1 and synaptobrevin-2, are expressed at the developing neuromuscular junction (NMJ) in mice, but their specific roles in NMJ formation and function remain unclear. Here, we examine the NMJs in mutant mouse embryos lacking either synaptobrevin 1 (Syb1lew/lew ) or synaptobrevin 2 (Syb2-/-), and those lacking both (Syb1lew/lewSyb2-/-). We found that, compared with controls: (1) the number and size of NMJs was markedly increased in Syb2-/- and Syb1lew/lewSyb2-/- mice, but not in Syb1lew/lew mice; (2) synaptic vesicle density was markedly reduced in Syb1lew/lewSyb2-/- NMJs; and (3) evoked neurotransmission was markedly reduced in Syb2-/- NMJs and completely abolished in Syb1lew/lewSyb2-/- NMJs. Surprisingly, however, spontaneous neurotransmission persists in the absence of both Syb1 and Syb2. Furthermore, spontaneous neurotransmission remains constant in Syb1lew/lewSyb2-/- NMJs despite changing Ca2+ levels. These findings reveal an overlapping role for Syb1 and Syb2 (with Syb2 being dominant) in developing NMJs in mice. Moreover, because spontaneous release becomes Ca2+-insensitive in Syb1lew/lewSyb2-/- NMJs, our findings suggest that synaptobrevin-based SNARE complexes play a critical role in conferring Ca2+ sensitivity during spontaneous release.SIGNIFICANCE STATEMENT Neurotransmitters can be released at synapses with (evoked) or without (spontaneous) the influence of action potentials. Whereas evoked neurotransmission requires Ca2+ influx, those underlying the spontaneous neurotransmission may occur with or without Ca2+ Our findings show that, in the absence neuronal vSNARE synaptobrevin-1 and synaptobrevin-2, evoked neurotransmission is completely abolished; however, spontaneous synaptic transmission not only persists but even increased. Furthermore, spontaneous synaptic transmission that is normally highly Ca2+-sensitive became Ca2+-independent upon deletion of vSNARE synaptobrevin-1 and synaptobrevin-2. These findings reveal distinct mechanisms for evoked and spontaneous neurotransmitter release. Moreover, these findings suggest that synaptobrevin-based SNARE complexes play critical roles in conferring Ca2+ sensitivity during spontaneous neurotransmission at developing neuromuscular synapses in mice.
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Unión Neuromuscular/metabolismo , Neurotransmisores/metabolismo , Proteínas R-SNARE/metabolismo , Transmisión Sináptica/fisiología , Animales , Embrión de Mamíferos , Ratones , Ratones Noqueados , Neurogénesis/fisiología , Unión Neuromuscular/embriología , SinapsisRESUMEN
Diabetic foot ulcers (DFUs) caused by diabetes are prone to serious and persistent infections. If not treated properly, it will cause tissue necrosis or septicemia due to peripheral blood vessel embolism. Therefore, it is an urgent challenge to accelerate wound healing and reduce the risk of bacterial infection in patients. In clinical practice, DFUs mostly use hydrogel dressing to cover the surface of the affected area as an auxiliary treatment. Polyvinyl alcohol (PVA) is a hydrophilic hydrogel polymer widely used in dressings, drug delivery, and medical applications. However, due to its weak bioactivity and antibacterial ability, leads to limited application. Filler adding is a useful way to enhance the biocompatibility of PVA. In our study, cobalt-substituted hydroxyapatite (CoHA) powder was prepared by the electrochemically-deposited method. PVA and PVA-CoHA nanocomposite were prepared by the solvent casting method. The bioactivity of the PVA and composite was evaluated by immersed in simulated body fluid for 7 days. In addition, L929 cells and E. coli were used to evaluate the cytotoxicity and antibacterial tests of PVA and PVA-CoHA nanocomposite. The results show that the addition of CoHA increases the mechanical properties and biological activity of PVA. Biocompatibility evaluation showed no significant cytotoxicity of PVA-CoHA composite. In addition, a small amount of cobalt ion was released to the culture medium from the nanocomposite in the cell culture period and enhanced cell growth. The addition of CoHA also confirmed that it could inhibit the growth of E. coli. PVA-CoHA composite may have potential applications in diabetic trauma healing and wound dressing.
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Vendajes , Cobalto/farmacología , Pie Diabético/terapia , Nanocompuestos/química , Alcohol Polivinílico/farmacología , Animales , Antibacterianos/farmacología , Línea Celular , Cobalto/química , Pie Diabético/fisiopatología , Durapatita , Escherichia coli/efectos de los fármacos , Hidrogeles , Ratones , Alcohol Polivinílico/química , Cicatrización de HeridasRESUMEN
OBJECTIVE: Bereavement care is one of the major components of hospice palliative care. Previous studies revealed the barriers to the success of the system, including lack of time or support from mental health professionals. Few studies have explored the intrapersonal barriers to bereavement care by clinical staff. The aims of the study were to explore (1) the emotional and cognitive barriers of bereavement care by hospice palliative care staff and (2) the demographic and work characteristics related to these emotional and cognitive barriers. METHOD: The participants were clinical staff (n = 301) who were working in hospice palliative care units, including hospice wards, home care, and hospital-based palliative care teams. Their professional backgrounds included physicians (n = 12), nurses (n = 172), social workers (n = 59), psychologists (n = 34), spiritual care specialists (n = 15), and others (n = 9). A cross-sectional design was used and a standardized questionnaire including emotional and cognitive barriers was developed. Information on demographic and work characteristics was also collected. Content validity index, an exploratory factor analysis, and multiple regression analysis were conducted. RESULTS: One emotional barrier, "negative emotional reactions" (13 items, Cronbach's α = 0.92), and three cognitive barriers, "lack of ability" (7 items, Cronbach's α = 0.85), "belief in avoidance" (5 items, Cronbach's α = 0.86), and "outcome expectancy" (4 items, Cronbach's α = 0.85) were identified. Clinical staff who had higher working stress, lower self-rated ability for bereavement care, and higher negative impact from major life loss tended to have higher emotional and cognitive barriers. SIGNIFICANCE OF RESULTS: Clinical staff should be aware of intrapersonal barriers to bereavement care. Educational programs should be developed to improve the ability to engage in bereavement care.
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Personal de Salud/psicología , Cuidados Paliativos al Final de la Vida/psicología , Cuidados Paliativos/normas , Adulto , Femenino , Personal de Salud/estadística & datos numéricos , Cuidados Paliativos al Final de la Vida/métodos , Cuidados Paliativos al Final de la Vida/normas , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
Innervation of skeletal muscle by motor neurons occurs through the neuromuscular junction, a cholinergic synapse essential for normal muscle growth and function. Defects in nerve-muscle signaling cause a variety of neuromuscular disorders with features of ataxia, paralysis, skeletal muscle wasting, and degeneration. Here we show that the nuclear zinc finger protein ZFP106 is highly enriched in skeletal muscle and is required for postnatal maintenance of myofiber innervation by motor neurons. Genetic disruption of Zfp106 in mice results in progressive ataxia and hindlimb paralysis associated with motor neuron degeneration, severe muscle wasting, and premature death by 6 mo of age. We show that ZFP106 is an RNA-binding protein that associates with the core splicing factor RNA binding motif protein 39 (RBM39) and localizes to nuclear speckles adjacent to spliceosomes. Upon inhibition of pre-mRNA synthesis, ZFP106 translocates with other splicing factors to the nucleolus. Muscle and spinal cord of Zfp106 knockout mice displayed a gene expression signature of neuromuscular degeneration. Strikingly, altered splicing of the Nogo (Rtn4) gene locus in skeletal muscle of Zfp106 knockout mice resulted in ectopic expression of NOGO-A, the neurite outgrowth factor that inhibits nerve regeneration and destabilizes neuromuscular junctions. These findings reveal a central role for Zfp106 in the maintenance of nerve-muscle signaling, and highlight the involvement of aberrant RNA processing in neuromuscular disease pathogenesis.
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Proteínas Adaptadoras Transductoras de Señales/genética , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Síndrome Debilitante/genética , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Animales , Células COS , Chlorocebus aethiops , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Noqueados , Ratones Transgénicos , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Desnervación Muscular , Músculo Esquelético/inervación , Músculo Esquelético/patología , Atrofia Muscular/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Síndrome Debilitante/metabolismoRESUMEN
The purpose of this pilot study was to assess the feasibility and usability of an ecological momentary assessment smartphone application. The app collected real-time data on chronic low back pain and time-contingent ecological momentary assessment surveys during a 4-week auricular point acupressure intervention, and on the consistency between recalled and momentary clinical measures. Eighteen participants received auricular point acupressure treatment weekly for 4 weeks. Each participant was provided a smartphone with the ecological momentary assessment application installed, along with instructions for use. The primary outcomes comprised pain intensity, pain interference with daily activity, sleep quality score, and medication usage. System Usability Scale and adherence were also measured. According to the results, the rate of adherence for completion of the random ecological momentary assessment survey was 87%. The usability score for the ecological momentary assessment application was reported as 78. The average recalled pain intensity was higher than the mean momentary pain intensity. Self-reported average pain interference with daily activities showed a similar result. Spearman rank correlation coefficients were greater than +0.70; P < .01 for the associations among recalled and momentary measurements. In conclusion, the study demonstrated promising adherence rates and supported the usability and feasibility of using an ecological momentary assessment application on a smartphone to collect real-time data on chronic lower back pain, which eliminated recall bias.
Asunto(s)
Acupresión/normas , Dolor de la Región Lumbar/terapia , Acupresión/métodos , Adulto , Anciano , Dolor Crónico/terapia , Evaluación Ecológica Momentánea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
Primary cilia have been implicated in the generation of planar cell polarity (PCP). However, variations in the severity of polarity defects in different cilia mutants, coupled with recent demonstrations of non-cilia-related actions of some cilia genes, make it difficult to determine the basis of these polarity defects. To address this issue, we evaluated PCP defects in cochlea from a selection of mice with mutations in cilia-related genes. Results indicated notable PCP defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and Ift20 single mutants that are more severe than in other cilia gene knockouts. In addition, deletion of either Bbs8 or Ift20 results in disruptions in asymmetric accumulation of the core PCP molecule Vangl2 in cochlear cells, suggesting a role for Bbs8 and/or Ift20, possibly upstream of core PCP asymmetry. Consistent with this, co-immunoprecipitation experiments indicate direct interactions of Bbs8 and Ift20 with Vangl2. We observed localization of Bbs and Ift proteins to filamentous actin as well as microtubules. This could implicate these molecules in selective trafficking of membrane proteins upstream of cytoskeletal reorganization, and identifies new roles for cilia-related proteins in cochlear PCP.
Asunto(s)
Proteínas Portadoras/metabolismo , Polaridad Celular/fisiología , Cilios/genética , Cóclea/embriología , Proteínas Asociadas a Microtúbulos/metabolismo , Animales , Cilios/fisiología , Cilios/ultraestructura , Cóclea/ultraestructura , Proteínas del Citoesqueleto , Células Ciliadas Auditivas/patología , Inmunohistoquímica , Inmunoprecipitación , Ratones , Ratones Noqueados , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Proteínas del Tejido NerviosoRESUMEN
We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1lew/lew mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597-603.