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1.
Biomaterials ; 313: 122767, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39216327

RESUMEN

Peripheral artery disease is commonly treated with balloon angioplasty, a procedure involving minimally invasive, transluminal insertion of a catheter to the site of stenosis, where a balloon is inflated to open the blockage, restoring blood flow. However, peripheral angioplasty has a high rate of restenosis, limiting long-term patency. Therefore, angioplasty is sometimes paired with delivery of cytotoxic drugs like paclitaxel to reduce neointimal tissue formation. We pursue intravascular drug delivery strategies that target the underlying cause of restenosis - intimal hyperplasia resulting from stress-induced vascular smooth muscle cell switching from the healthy contractile into a pathological synthetic phenotype. We have established MAPKAP kinase 2 (MK2) as a driver of this phenotype switch and seek to establish convective and contact transfer (coated balloon) methods for MK2 inhibitory peptide delivery to sites of angioplasty. Using a flow loop bioreactor, we showed MK2 inhibition in ex vivo arteries suppresses smooth muscle cell phenotype switching while preserving vessel contractility. A rat carotid artery balloon injury model demonstrated inhibition of intimal hyperplasia following MK2i coated balloon treatment in vivo. These studies establish both convective and drug coated balloon strategies as promising approaches for intravascular delivery of MK2 inhibitory formulations to improve efficacy of balloon angioplasty.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Proteínas Serina-Treonina Quinasas , Ratas Sprague-Dawley , Animales , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Péptidos/química , Péptidos/farmacología , Ratas , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/citología , Angioplastia de Balón/métodos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Sistemas de Liberación de Medicamentos , Hiperplasia/prevención & control , Angioplastia , Neointima/prevención & control , Neointima/patología
2.
Pain Ther ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240480

RESUMEN

INTRODUCTION: Chronic post-surgical pain (CPSP) remains a prevalent issue following video-assisted thoracic surgery (VATS), despite advancements in surgical techniques. Various regional anesthesia techniques, including thoracic paravertebral block (PVB), intercostal nerve block (ICNB), serratus anterior plane block (SAPB), erector spinae plane block (ESPB), and thoracic epidural anesthesia (TEA), have been employed in VATS procedures to mitigate this issue. This study aims to compare the efficacy of these analgesia methods in reducing the incidence of CPSP in VATS patients through a network meta-analysis. METHODS: A systematic search was conducted in PubMed, the Cochrane Library, and EMBASE for randomized controlled trials (RCTs) comparing the incidence of CPSP associated with PVB, ICNB, SAPB, ESPB, and TEA. The occurrence of CPSP was evaluated at both 2-3 months and 6 months post-surgery. RESULTS: Six RCTs, involving 652 patients, were included in the analysis of CPSP incidence at 2-3 months, while seven RCTs, involving 715 patients, were included for 6 months analysis. PVB, ICNB, or TEA reduced CPSP incidence compared with control group (without regional anesthesia techniques) at both 2-3 months and 6 months post-surgery. However, SAPB was found less effective in reducing CPSP incidence at 2-3 months post-VATS compared to PVB, ICNB, or TEA. CONCLUSIONS: PVB, ICNB, and TEA exhibit significant effects on reducing CPSP incidence following VATS. Conversely, SAPB is not recommended for reducing CPSP incidence post-VATS. Nonetheless, considering the limitation of a small sample size in this network meta-analysis, additional RCTs are necessary to validate these conclusions and enhance the management of CPSP after VATS.

3.
Clin Case Rep ; 12(9): e9412, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39238508

RESUMEN

We report a rare case of thyroid diffuse large B-cell lymphoma with a BRAF V600E mutation, which mimics poorly differentiated thyroid cancer in fine needle aspiration cytology.

4.
J Orthop Surg Res ; 19(1): 533, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39218944

RESUMEN

BACKGROUND: The reconstruction of complex wounds of the hand still has challenges in achieving aesthetic, functional and sensory recovery. We presented our experience of using the polyfoliate and chimeric radial collateral artery perforator flaps (RCAPF) to repair complex hand defects, aiming to explore the feasibility of special-form RCAPFs in hand coverage and enhance the comprehension of their respective indications. METHODS: From June 2014 to March 2021, 26 cases (19 males and 7 females, mean 44.4 years) underwent defect and sensation reconstruction of their hands with special-form RCAPFs, which manifested as multiple adjacent or irregular single wounds and composite tissue defects complicated with a degree of nerve injury. The clinical effects of the free RCAPFs were evaluated by integrating the postoperative and long-term follow-up outcomes of all cases. RESULTS: Altogether 8 polyfoliate flaps, 17 chimeric flaps and 1 polyfoliate-chimeric flap were harvested. Of them, 23 flaps survived uneventfully in one stage. Venous congestion occurred in 3 cases, two of which survived through vascular exploration and another one was finally repaired by the contralateral RCAPF. The follow-up results showed that the appearance of both the recipient and donor sites mostly recovered satisfactory. All the bone flaps properly healed. The BMRC sensory evaluation results of all skin flaps were S4 in 8 flaps, S3 in 18 flaps, and S2 in 9 flaps. CONCLUSIONS: The free RCAPFs can be designed in various forms with a reliable blood supply, contributing to reconstructing simple and multiple wounds of the hand with or without bone defects and dead space.


Asunto(s)
Traumatismos de la Mano , Colgajo Perforante , Procedimientos de Cirugía Plástica , Arteria Radial , Humanos , Femenino , Masculino , Colgajo Perforante/irrigación sanguínea , Adulto , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Arteria Radial/trasplante , Traumatismos de la Mano/cirugía , Mano/cirugía , Mano/irrigación sanguínea , Adulto Joven , Estudios de Seguimiento , Resultado del Tratamiento , Estudios de Factibilidad
5.
Nanoscale ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225229

RESUMEN

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of CoN (N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e., Co13, Co19, Co22, Co39, and Co43, were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

6.
Acta Pharmacol Sin ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284878

RESUMEN

Chronic itch is a maladaptive and debilitating symptom in patients with allergic contact dermatitis (ACD), adversely affecting their quality of life. There is a lack of effective treatments for ACD-associated uncontrollable itch. In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD. The ACD mice were intraperitoneally injected with BE (5, 30, and 60 mg·kg-1·d-1) for 7 days during the DCP challenge phase. The results showed that DCP-treated mice exhibited severe spontaneous scratching behaviors that was reduced after BE injections in a dose-dependent manner accompanied by inhibition of spinal astrocyte activation. We observed that the spinal astrocytic STAT3-LCN2 cascade plays a crucial role in controlling the activation of astrocytes in chronic itch. Intrathecal injection of the STAT3 inhibitor AG490 or Lcn2 siRNA significantly reduced scratching behavior and astrocyte activation in ACD mice. Moreover, BE markedly attenuated the increased phosphorylation of STAT3 (p-STAT3) and LCN2 expression in the spinal cords of ACD mice and in lipopolysaccharide-stimulated primary spinal astrocytes. Altogether, BE relieved chronic itch by suppressing the spinal astrocytic STAT3-LCN2 cascade. These findings provide a potential avenue for the management of chronic itch. Schematic summary of the main findings illustrating that BE alleviates chronic itch through suppressing the spinal astrocytic STAT3-LCN2 cascade. Specifically, BE suppresses the expression of p-STAT3 to inhibit the reactive state of astrocytes in spinal dorsal horn, and then decreases the expression of astrocytic LCN2 to alleviate chronic itch in ACD mice.

7.
Int J Gen Med ; 17: 3955-3965, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268179

RESUMEN

Aim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations. Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations. Results: We found that gender were associated with 25(OH)D, OC, ß-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P<0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in ß- CTX levels between seasons. Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.

8.
Angle Orthod ; 94(4): 441-447, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39229954

RESUMEN

OBJECTIVES: To compare upper airway changes following bimaxillary surgery for correction of Class III deformity between patients with unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) and to compare the preoperative and postoperative upper airway among patients with UCLP and BCLP to healthy controls. MATERIALS AND METHODS: Sixty adults with CLP-related skeletal Class III deformity (30 UCLP and 30 BCLP) who consecutively underwent bimaxillary surgery were studied retrospectively. Cone-beam computed tomography (CBCT) was performed before and after surgery to measure upper airway and movements of facial skeletal and surrounding structures. CBCT images from 30 noncleft skeletal Class I adults, matched by age, gender, and body mass index and without surgical intervention, served as controls. RESULTS: After surgery, the volume of the nasopharynx increased in patients with CLP (both P < .001). Patients with CLP did not differ from controls in postoperative volume of the nasopharynx or oropharynx. However, the nasal cavity differed significantly between patients with CLP and controls (P < .001). CONCLUSIONS: After bimaxillary surgery, the nasal cavity of patients with CLP differed significantly compared with the controls. Volumes of the nasopharynx and oropharynx did not differ between patients with CLP after surgery and controls.


Asunto(s)
Labio Leporino , Fisura del Paladar , Tomografía Computarizada de Haz Cónico , Maloclusión de Angle Clase III , Maxilar , Nasofaringe , Humanos , Femenino , Masculino , Tomografía Computarizada de Haz Cónico/métodos , Fisura del Paladar/cirugía , Fisura del Paladar/diagnóstico por imagen , Labio Leporino/cirugía , Labio Leporino/diagnóstico por imagen , Maloclusión de Angle Clase III/cirugía , Maloclusión de Angle Clase III/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Nasofaringe/diagnóstico por imagen , Maxilar/cirugía , Maxilar/diagnóstico por imagen , Procedimientos Quirúrgicos Ortognáticos/métodos , Orofaringe/diagnóstico por imagen , Adulto Joven , Cavidad Nasal/diagnóstico por imagen , Estudios de Casos y Controles , Adolescente , Resultado del Tratamiento
9.
Compend Contin Educ Dent ; 45(8): 428-429, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39276792

RESUMEN

Nutrition has been recognized as a foundation for good oral health and general health, with a bidirectional relationship having been established between nutrition and oral and overall health.1 Various specific macro- and micronutrients from the intake of food serve as fuel for a person's body to grow and function.1 The oral cavity plays the unique role of gatekeeper, providing the pathway of nutrition to the body. Because of the rapid cell turnover of oral mucosa, the oral cavity also may manifest early signs of nutrient deficiencies as well as other indicators of systemic disease.2 As a result, problems in the oral cavity can profoundly affect one's appetite, desire and ability to eat, and, consequently, nutritional status and overall health.1.


Asunto(s)
Estado Nutricional , Enfermedades Periodontales , Humanos , Salud Bucal
10.
J Neuroimmunol ; 396: 578447, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39255718

RESUMEN

Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder where acetylcholine receptor (AChR) antibodies induce membrane attack complex formation at the muscle membrane. The C1-inhibitor (C1-INH) regulates the classical pathway and is a promising marker in other autoimmune disorders. Treatment options for AChR antibody MG include complement inhibitors; nevertheless, the early pathway activation in MG remains unclear. Serum and plasma C1s-C1-INH levels were higher in MG patients than in matched healthy controls, supporting early classical pathway activation in most MG patients. These findings allow prospective validation studies of activated C1s as a putative treatment target and potential accompanying biomarker in MG.

11.
J Hazard Mater ; 479: 135536, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39191015

RESUMEN

This study investigated the influence of photoaging on a nanoscale metal-organic framework (MOF), truncated rhombic dodecahedron nano-zeolitic imidazolate framework-8 (nZIF-8), focusing on its oxidative stress, inflammation, and implications for pulmonary diseases. We observed significant photodegradation-induced transformations in nZIF-8, characterized by a reduction in particle size from 200.5 to 101.4 nm and notable structural disintegration after prolonged exposure to simulated solar radiation. This alteration resulted in a marked decrease in oxidative cytotoxicity in BEAS-2B cells, which was attributed to changes in surface properties and reduced reactive oxygen species (ROS) production. Gene expression analysis further revealed a decrease in cytotoxic and inflammatory responses, which potentially lowers the risk of chronic obstructive pulmonary disease (COPD). Aged nZIF-8 also showed diminished capacity to induce pro-inflammatory cytokines and influence COPD-related gene expression, reducing its potential to exacerbate COPD pathogenesis. Our findings highlight the critical need for comprehensive safety evaluations of these materials, while considering their long-term environmental and biological impacts. The diminished cytotoxicity and inflammatory potential of aged nZIF-8 highlighted its enhanced suitability for broader applications, indicating that photoaging may lead to safer and more sustainable material utilization.

12.
Phytomedicine ; 133: 155885, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39096544

RESUMEN

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Angiotensina II , Endotelio Vascular , Células Endoteliales de la Vena Umbilical Humana , Hipertensión , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III , Óxido Nítrico , Angiotensina II/farmacología , Animales , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Hipertensión/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Ratones , Salvia/química , Endotelina-1/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Quinonas/farmacología , Simulación del Acoplamiento Molecular , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad
13.
J Transl Med ; 22(1): 743, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107765

RESUMEN

BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.


Asunto(s)
Insuficiencia Cardíaca , Modelos de Riesgos Proporcionales , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Femenino , Masculino , Anciano , Reproducibilidad de los Resultados , Pronóstico , Análisis de Supervivencia , Persona de Mediana Edad , Curva ROC , Algoritmos , Área Bajo la Curva , Bases de Datos Factuales , Aprendizaje Profundo , Índice de Severidad de la Enfermedad
14.
J Clin Immunol ; 44(8): 176, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133333

RESUMEN

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.


Asunto(s)
Autoanticuerpos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Nocardiosis , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Nocardiosis/inmunología , Nocardiosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Proteinosis Alveolar Pulmonar/inmunología , Proteinosis Alveolar Pulmonar/diagnóstico , Cryptococcus gattii/inmunología
15.
Muscle Nerve ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115039

RESUMEN

INTRODUCTION/AIMS: There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells. METHODS: We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. RESULTS: MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. DISCUSSION: We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.

16.
J Gerontol Nurs ; 50(9): 31-36, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39194322

RESUMEN

PURPOSE: To analyze cardiorespiratory fitness (CRF) levels using the gold-standard, laboratory-based cardiopulmonary exercise test (CPET) in community-dwelling older adults (N = 145) with amnestic mild cognitive impairment (aMCI), specifically CPET feasibility, CRF prediction, and CRF status in comparison to published sedentary, cognitively normal, age- and sex-adjusted normative data. METHOD: Peak oxygen consumption (VO2Peak [mL/kg/min]) was assessed by CPET, which was categorized as submaximal, near-maximal, or maximal tests. VO2Max predicted was compared to VO2Max measured to assess its utility. Data were analyzed with t tests. RESULTS: Participants' mean age was 73.77 years (SD = 5.74 years), with 51.7% males, 91.7% Caucasian, 68.3% married, and 16.9 years (SD = 2.88 years) of education. Mean VO2Peak measured was 17.07 (SD = 4.92) for the total sample (18.29 [SD = 4.64] for males, 15.78 [SD = 4.91] for females). Sixteen (11.03%) CPETs were submaximal, 53 (36.55%) were near-maximal, and 76 (52.41%) were maximal. Mean VO2Max predicted was 28.59 (SD = 21.94) for the total sample (29.36 [SD = 22.3] for males, 27.76 [SD = 21.68] for females) and was significantly higher than VO2Max measured (p < 0.0001). Among participants with maximal CPETs, VO2Peak measured was significantly lower than sedentary normative data (p < 0.0001). CONCLUSION: CPET was feasible for older adults with aMCI. VO2Max predicted overly inflates CRF estimates. Low levels of CRF in older adults with aMCI suggest aerobic exercise as an important intervention. [Journal of Gerontological Nursing, 50(9), 31-36.].


Asunto(s)
Enfermedad de Alzheimer , Capacidad Cardiovascular , Disfunción Cognitiva , Prueba de Esfuerzo , Humanos , Masculino , Femenino , Anciano , Disfunción Cognitiva/fisiopatología , Capacidad Cardiovascular/fisiología , Enfermedad de Alzheimer/fisiopatología , Prueba de Esfuerzo/métodos , Anciano de 80 o más Años , Consumo de Oxígeno , Ejercicio Físico
17.
Clin Oral Investig ; 28(9): 502, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196436

RESUMEN

OBJECTIVES: To compare the facial asymmetry after bimaxillary surgery between mild craniofacial microsomia (CFM) and non-syndromic class II asymmetry. MATERIALS AND METHODS: Cone-beam computed tomography scans of adults with Pruzansky-Kaban types I and IIA CFM (CFM groups, n = 20), non-syndromic skeletal class II asymmetry (Class II group, n = 20), and normal controls (control group, n = 20) were compared. The area asymmetry of lower face and jaw bones was quantified. Landmark-based method was used to evaluate the lower facial asymmetry regarding midline, cants, and contour. RESULTS: There were no significant postoperative differences in the hemi-facial and hemi-jaw area asymmetry between CFM and Class II groups, both of which were significantly larger than the control group. No significant difference was found in the midline deviation and lip and occlusal cants between CFM and Class II groups. The vertical contour asymmetry in CFM group became significantly larger than Class II group. Compared to the control group, the deviation of pronasale, subnasale, and soft-tissue menton, lip and occlusal cants, and sagittal and vertical contour asymmetry in CFM group were significantly larger, as were the deviation of subnasale and soft-tissue menton and vertical contour asymmetry in Class II group. CONCLUSIONS: The vertical contour asymmetry of mild CFM was significantly larger than non-CFM class II after surgery, while the area asymmetry, midline deviation, cants, and sagittal contour asymmetry of lower face showed no significant difference. CLINICAL RELEVANCE: Be aware that correcting vertical asymmetry of contour, lip, and dentition in CFM is still challenging.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Asimetría Facial , Síndrome de Goldenhar , Maloclusión Clase II de Angle , Procedimientos Quirúrgicos Ortognáticos , Humanos , Asimetría Facial/cirugía , Asimetría Facial/diagnóstico por imagen , Masculino , Procedimientos Quirúrgicos Ortognáticos/métodos , Femenino , Maloclusión Clase II de Angle/cirugía , Maloclusión Clase II de Angle/diagnóstico por imagen , Adulto , Síndrome de Goldenhar/diagnóstico por imagen , Síndrome de Goldenhar/cirugía , Resultado del Tratamiento , Puntos Anatómicos de Referencia , Adolescente , Estudios de Casos y Controles
18.
Artículo en Inglés | MEDLINE | ID: mdl-39160115

RESUMEN

BACKGROUND: Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated. METHODS: Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells. RESULTS: In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis. CONCLUSION: Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by C. jejuni CDT.

19.
J Colloid Interface Sci ; 678(Pt A): 141-151, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39182388

RESUMEN

Luminescent materials with engineered optical properties play an important role in anti-counterfeiting and information security technology. However, conventional luminescent coding is limited by fluorescence color or intensity, and high-level multi-dimensional luminescent encryption technology remains a critically challenging goal in different scenarios. To improve the encoding capacity, we present an optical multiplexing concept by synchronously manipulating the emission color and decay lifetimes of room-temperature phosphorescence materials at molecular level. Herein, we devise a family of zero-dimensional (0D) hybrid metal halides by combining organic phosphonium cations and metal halide tetrahedral anions as independent luminescent centers, which display blue phosphorescence and green persistent afterglow with the highest quantum yields of 39.9 % and 57.3 %, respectively. Significantly, the luminescence lifetime can be fine-tuned in the range of 0.0968-0.5046 µs and 33.46-125.61 ms as temporary time coding through precisely controlling the heavy atomic effect and inter-molecular interactions. As a consequence, synchronous blue phosphorescence and green afterglow are integrated into one 0D halide platform with adjustable emission lifetime acting as color- and time-resolved dual RTP materials, which realize the multiple applications in high-level anti-counterfeiting and information storage. The color-lifetime-dual-resolved encoding ability greatly broadens the scope of luminescent halide materials for optical multiplexing applications.

20.
World Neurosurg ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39182833

RESUMEN

OBJECTIVE: To evaluate the effects of a multimodal management technique combining surgical muscle wrapping, clipping, and flow-diverter stent (FDS) placement in patients with ruptured blood blister-like aneurysms (BBAs) in the internal carotid artery (ICA). METHODS: In a retrospective case series review from 2020 to 2023, three patients with ruptured ICA BBAs underwent multimodal management, an approach combining muscle wrapping, surgical clipping, and FDS embolization. The aneurysm sac was initially packed and wrapped with multiple tailored temporalis muscle grafts and then secured using fenestration clips, with good preservation of the ICA branches. The FDS was placed 2-3 weeks after the clipping. RESULTS: All three patients had right ICA BBAs (mean age, 52 years). The modified Hunt and Hess grades ranged from 2 to 3, and the Fisher grades ranged from 3 to 4. The mean angiography follow-up time was 27.7 months (15, 31, and 37 months). There were no instances of symptomatic vasospasm or visible ischemic stroke during follow-up computed tomography. No patient required cerebrospinal fluid shunt implantation, and all achieved favorable neurological outcomes (modified Rankin Scale 0-1). Follow-up digital subtraction angiography revealed no evidence of aneurysm recurrence or significant ICA stenosis. CONCLUSIONS: We discuss a promising multimodal management approach for ruptured ICA BBAs combining muscle wrapping, surgical clipping, and FDS embolization. This technique was safe and effective in preventing re-rupture, achieving positive short-term clinical outcomes. Further research and more extensive studies are required to validate the long-term efficacy of this approach.

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