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1.
Cell Host Microbe ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38959900

RESUMEN

The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain understudied. Alcohol-related liver disease (ALD) is one such disease with limited therapeutic options due to its complex pathogenesis. We demonstrate that a diet rich in soluble dietary fiber increases the abundance of Bacteroides acidifaciens (B. acidifaciens) and alleviates alcohol-induced liver injury in mice. B. acidifaciens treatment alone ameliorates liver injury through a bile salt hydrolase that generates unconjugated bile acids to activate intestinal farnesoid X receptor (FXR) and its downstream target, fibroblast growth factor-15 (FGF15). FGF15 promotes hepatocyte expression of ornithine aminotransferase (OAT), which facilitates the metabolism of accumulated ornithine in the liver into glutamate, thereby providing sufficient glutamate for ammonia detoxification via the glutamine synthesis pathway. Collectively, these findings uncover a potential therapeutic strategy for ALD involving dietary fiber supplementation and B. acidifaciens.

2.
Front Cell Dev Biol ; 12: 1406830, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38946798

RESUMEN

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

3.
BMC Musculoskelet Disord ; 25(1): 506, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943135

RESUMEN

BACKGROUND: Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing. METHODS: In the control group, 8 male Sprague-Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05. RESULTS: The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear. CONCLUSION: The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.


Asunto(s)
Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Lesiones del Manguito de los Rotadores , Animales , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/fisiopatología , Lesiones del Manguito de los Rotadores/diagnóstico , Proyectos Piloto , Masculino , Ratas , Análisis de la Marcha/métodos , Manguito de los Rotadores/cirugía , Manguito de los Rotadores/fisiopatología , Marcha/fisiología , Recuperación de la Función
4.
Cancer Med ; 13(12): e7213, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38888352

RESUMEN

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.


Asunto(s)
Procedimientos Quirúrgicos Electivos , Tiempo de Internación , Neoplasias de la Boca , Traqueotomía , Humanos , Traqueotomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Pronóstico , Anciano , Procedimientos Quirúrgicos Electivos/métodos , Tiempo de Internación/estadística & datos numéricos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Adulto
5.
Bioact Mater ; 39: 255-272, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38832304

RESUMEN

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor ß (TGFß) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFß inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFß1 (as those levels found in patients' synovial fluid). A monthly injection strategy was then designed of using poly lactic-co-glycolic acid (PLGA) microparticles and hyaluronic acid (HA) solution to enable a sustained release of PFD (the "PLGA-PFD + HA" strategy). This strategy effectively regulated OA progression in destabilization of the medial meniscus (DMM)- induced OA mice model, including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA, and reduced synovitis and pain with cartilage preservation effects. This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

6.
Int J Med Robot ; 20(3): e2655, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38922786

RESUMEN

BACKGROUND: Up to 20% of patients remain unsatisfied after total knee arthroplasty (TKA), prompting the development of new implants. Bi-Cruciate Retaining (BCR) TKA preserves both the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL), with the ACL beneficial for its proprioceptive qualities. The Bi-Cruciate Stabilised (BCS) TKA substitutes the ACL and PCL with a unique dual cam-post mechanism. Robotics improve accuracy and facilitate technically demanding TKA. METHODS: This was a retrospective case-control study recruited from two centres. Measured outcomes included kinematic analysis, proprioception, and functional outcomes. RESULTS: There was a significantly larger maximum flexion angle and range of flexion to extension in sit-to-stand and stairs in BCR when compared to BCS. Further analysis revealed more similarities between BCR and normal native knees. Proprioception and functional scores did not have any statistical difference. CONCLUSION: BCR TKA demonstrated better knee flexion in weight-bearing active range of motion and showed similarities with normal knee kinematics.


Asunto(s)
Ligamento Cruzado Anterior , Artroplastia de Reemplazo de Rodilla , Articulación de la Rodilla , Ligamento Cruzado Posterior , Rango del Movimiento Articular , Procedimientos Quirúrgicos Robotizados , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Fenómenos Biomecánicos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Ligamento Cruzado Posterior/cirugía , Estudios de Casos y Controles , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/fisiopatología , Ligamento Cruzado Anterior/cirugía , Ligamento Cruzado Anterior/fisiopatología , Prótesis de la Rodilla , Resultado del Tratamiento , Propiocepción
7.
Diagnostics (Basel) ; 14(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38928678

RESUMEN

Scoliosis, characterized by spine deformity, is most common in adolescent idiopathic scoliosis (AIS). Manual Cobb angle measurement limitations underscore the need for automated tools. This study employed a vertebral landmark extraction method and Feedforward Neural Network (FNN) to predict scoliosis progression in 79 AIS patients. The novel intervertebral angles matrix format showcased results. The mean absolute error for the intervertebral angle progression was 1.5 degrees, while the Pearson correlation of the predicted Cobb angles was 0.86. The accuracy in classifying Cobb angles (<15°, 15-25°, 25-35°, 35-45°, >45°) was 0.85, with 0.65 sensitivity and 0.91 specificity. The FNN demonstrated superior accuracy, sensitivity, and specificity, aiding in tailored treatments for potential scoliosis progression. Addressing FNNs' over-fitting issue through strategies like "dropout" or regularization could further enhance their performance. This study presents a promising step towards automated scoliosis diagnosis and prognosis.

8.
Opt Lett ; 49(9): 2413-2416, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691732

RESUMEN

A novel, to the best of our knowledge, cross-spectral optical computing imaging experiment has been achieved through a single exposure of a charge-coupled device. The experimental setup integrates single-pixel imaging (SPI) with ghost imaging (GI) through a photoelectric conversion circuit and a synchronous modulation system. The experimental process involves modulation in one wavelength band (in SPI) and demodulation using the GI algorithm in another. Significantly, our approach utilizes optical computing demodulation, a departure from the conventional electronic demodulation in GI (SPI), which involves the convolution between the bucket optical signals and the modulated patterns on the digital micromirror device. A proof-of-concept cross-band imaging experiment from near-infrared to visible light has been carried out. The results highlight the system's ability to capture images at up to 20 frames per second using near-infrared illumination, which are then reconstructed in the visible light spectrum. This success not only validates the feasibility of our approach but also expands the potential applications in the SPI or GI fields, particularly in scenarios where two-dimensional detector arrays are either unavailable or prohibitively expensive in certain electromagnetic spectra such as x-ray and terahertz.

9.
Cancer Med ; 13(10): e7127, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38770540

RESUMEN

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.


Asunto(s)
Neoplasias de la Boca , Humanos , Masculino , Femenino , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Persona de Mediana Edad , Anciano , Taiwán/epidemiología , Estadificación de Neoplasias , Dosificación Radioterapéutica , Resultado del Tratamiento , Puntaje de Propensión , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Adulto , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
11.
Korean J Radiol ; 25(5): 459-472, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685736

RESUMEN

Hyperpolarized (HP) carbon-13 (13C) MRI represents an innovative approach for noninvasive, real-time assessment of dynamic metabolic flux, with potential integration into routine clinical MRI. The use of [1-13C]pyruvate as a probe and its conversion to [1-13C]lactate constitute an extensively explored metabolic pathway. This review comprehensively outlines the establishment of HP 13C-MRI, covering multidisciplinary team collaboration, hardware prerequisites, probe preparation, hyperpolarization techniques, imaging acquisition, and data analysis. This article discusses the clinical applications of HP 13C-MRI across various anatomical domains, including the brain, heart, skeletal muscle, breast, liver, kidney, pancreas, and prostate. Each section highlights the specific applications and findings pertinent to these regions, emphasizing the potential versatility of HP 13C-MRI in diverse clinical contexts. This review serves as a comprehensive update, bridging technical aspects with clinical applications and offering insights into the ongoing advancements in HP 13C-MRI.


Asunto(s)
Isótopos de Carbono , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/diagnóstico por imagen , Ácido Pirúvico
12.
Eur Radiol Exp ; 8(1): 46, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38594558

RESUMEN

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.


Asunto(s)
Ácido Pirúvico , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Ácido Pirúvico/metabolismo , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/radioterapia , Estudios Prospectivos , Espectroscopía de Resonancia Magnética con Carbono-13/métodos , Lactatos
13.
Trials ; 25(1): 251, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605374

RESUMEN

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Músculo Cuádriceps , Humanos , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Fuerza Muscular , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina D , Vitaminas , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad
14.
Nat Prod Res ; : 1-6, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587144

RESUMEN

Fungi have different genetic expression abilities and biosynthetic pathways under different cultivation conditions, which can produce various secondary metabolites. The "one strain many compounds" strategy is used to activate silent biosynthetic genes of fungi to produce various compounds, which is an effective method. In order to discover various new compounds in the edible fungus Pholiota nameko, a fermentation strategy involving precursor feeding and enzyme inhibitor addition has been employed. A new illudane sesquiterpene (1), along with one known indole diterpenoid alkaloid, cladosporine A (2) were isolated from the extracts of liquid culture of P. nameko. The new compound was identified by combination of 1D and 2D NMR, MS, optical rotation, and ECD calculations. We conducted experiments on the cytotoxicity of all isolated compounds on three cancer cell lines, but we did not observe any significant cytotoxicity (IC50 > 40 µM).

15.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38612656

RESUMEN

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young's modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.


Asunto(s)
Enfermedades Musculoesqueléticas , Tendinopatía , Traumatismos de los Tendones , Animales , Ratones , Regulación hacia Arriba , Microtomografía por Rayos X , Inflamación , Modelos Animales de Enfermedad
16.
Oral Oncol ; 151: 106745, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38460286

RESUMEN

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Preescolar , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estudios Retrospectivos , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/patología , Pronóstico , Neoplasias de Cabeza y Cuello/patología , Estadificación de Neoplasias
17.
Chem Biodivers ; 21(4): e202400290, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38389159

RESUMEN

Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.


Asunto(s)
Factor de Necrosis Tumoral alfa , Receptor Nicotínico de Acetilcolina alfa 7 , Humanos , Regulación hacia Arriba , Lipopolisacáridos/farmacología , Neuroinmunomodulación , Cumarinas/farmacología , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico
18.
Adv Orthop ; 2024: 5598107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38328468

RESUMEN

Background: Glenoid bone loss is a risk factor leading to the failure of arthroscopic Bankart repair. While 20-25% glenoid bone loss has long been considered the level to necessitate bony augmentation, recent studies indicate that 13.5% has a "subcritical" glenoid bone loss level, which is associated with decreased short- and medium-term functional scores. Few researchers worked on the long-term effect of "subcritical" or even less severe degrees of glenoid bone loss on redislocation rates and functional outcomes after arthroscopic Bankart repair. This study aimed to evaluate the effect of subcritical or less severe glenoid bone loss on redislocation rates and function after arthroscopic Bankart repair. Methods: A patient cohort who had undergone computed tomography (CT) of glenoid bone loss and arthroscopic Bankart repair over 15 years ago was reviewed. Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, redislocation after operation, mechanism of recurrence, and revision details were reviewed. Results: Seventy-five patients were reassessed 17.6 ± 1.9 years following initial surgery. The age at enrolment was 26.8 ± 8.3 years. Twenty-two (29%) patients of the 75 patients had a redislocation on long-term follow-up, though this was not related to glenoid bone loss severity. The impaired functional score was found in patients with initial glenoid bone loss of 7% or more on long-term follow-up: WOSI (physical symptoms): 0.98 ± 2.00 vs 2.25 ± 4.01, p=0.04 and WOSI (total): 0.79 ± 1.43 vs 1.88 ± 3.56, p=0.04. Conclusions: At a mean of 17.5 years following arthroscopic Bankart repair, redislocation occurs in over a quarter of 75 patients, and they are not related to initial glenoid bone loss severity. Impaired functional outcome is apparent in patients with initial glenoid bone loss of >7%, though this impairment does not seem sufficiently severe to warrant an alternative treatment approach.

19.
Brain Behav ; 14(1): e3348, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38376042

RESUMEN

BACKGROUND: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD). METHODS: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis was conducted to examine the complexity of MRI signals among brain regions. Three-dimensional (3D) convolutional neural networks (CNNs) were used, and the classification accuracy in each brain region was averaged to predict suicidality after sixfold cross-validation. RESULTS: We found brain regions with a mean accuracy above 75% to predict suicidality located mostly in default mode, fronto-parietal, and cingulo-opercular resting-state networks. The models with right amygdala and left caudate provided the most reliable accuracy in all cross-validation folds, indicating their neurobiological importance in late-life suicide. CONCLUSION: Combining CSE analysis and the 3D CNN, several brain regions were found to be associated with suicidality.


Asunto(s)
Ideación Suicida , Suicidio , Humanos , Anciano , Depresión/diagnóstico por imagen , Intento de Suicidio , Imagen por Resonancia Magnética , Entropía , Redes Neurales de la Computación
20.
Nat Commun ; 15(1): 333, 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184613

RESUMEN

In recent years, mechanical metamaterials have been developed that support the propagation of an intriguing variety of nonlinear waves, including transition waves and vector solitons (solitons with coupling between multiple degrees of freedom). Here we report observations of phase transitions in 2D multistable mechanical metamaterials that are initiated by collisions of soliton-like pulses in the metamaterial. Analogous to first-order phase transitions in crystalline solids, we observe that the multistable metamaterials support phase transitions if the new phase meets or exceeds a critical nucleus size. If this criterion is met, the new phase subsequently propagates in the form of transition waves, converting the rest of the metamaterial to the new phase. More interestingly, we numerically show, using an experimentally validated model, that the critical nucleus can be formed via collisions of soliton-like pulses. Moreover, the rich direction-dependent behavior of the nonlinear pulses enables control of the location of nucleation and the spatio-temporal shape of the growing phase.

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