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We report a metal/light-free aerobic oxidative C-C bond formation using sp3 C-H bond activation of tetrahydroisoquinolines catalyzed by flavin and iodine. The dual catalytic system enabled the oxidative Mannich and aza-Henry reactions by the cross-dehydrogenative coupling between two sp3 C-H bonds. Furthermore, the flavin-iodine-coupled catalysis was applied to the synthesis of pyrrolo[2,1-a]isoquinolines through the sequential oxidative 1,3-dipolar cycloaddition and dehydrogenative aromatization. The biomimetic flavin catalysis efficiently activates molecular oxygen; thus the non-metal dual catalytic system enables green oxidative transformation using molecular oxygen as an environmentally friendly terminal oxidant which generates benign water.
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PURPOSE: It is not uncommon for patients with hip disorders to present with pelvic obliquity (PO), and residual PO after total hip arthroplasty (THA) may not only affect hip joint function but also cause adjacent intervertebral joint disorders. This study aimed to investigate the postoperative PO impact on clinical outcomes and risk factors by comparing patients who had PO after THA to those who did not. METHODS: A single-center, retrospective cohort study was conducted. A total of 103 patients who underwent THA were included in this study from 2018 to 2020. Demographics, functional outcomes, and spinopelvic parameters were compared between post-THA PO of less than 2° (NT group, 55 patients) and PO of 2° or more (O group, 48 patients). Multivariate analysis was performed using factors with significant differences in univariate analysis. RESULTS: Postoperative Harris Hip Score Activity was significantly lower in the T group than in the NT group (p = 0.031). Preoperative PO was smaller in the NT group than in the T group (p = 0.001). Preoperative lumbar bending range (LBR) was significantly more flexible in the NT group than in the T group. In the logistic regression analysis, Age (odds ratio 0.957, 95% CI 0.923-0.993, p = 0.020), preoperative PO (odds ratio 1.490, 95% CI 1.100-2.020, p = 0.001), and LBR (odds ratio 0.848, 95% CI 0.756-0.951, p = 0.005) were found to be significant factors. CONCLUSION: Younger age and large preoperative PO, and poor lumbar spine mobility were identified as risk factors for residual postoperative PO.
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Artroplastia de Reemplazo de Cadera , Huesos Pélvicos , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Factores de Riesgo , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/etiología , Factores de Edad , Rango del Movimiento Articular , Articulación de la Cadera/cirugía , Articulación de la Cadera/fisiopatologíaRESUMEN
A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors.
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Albúminas , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Paclitaxel , Humanos , Masculino , Anciano , Carboplatino/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Albúminas/efectos adversos , Albúminas/administración & dosificación , Vasculitis por IgA/inducido químicamente , Vasculitis por IgA/diagnóstico , Inmunoglobulina A , Inhibidores de Puntos de Control Inmunológico/efectos adversosRESUMEN
BACKGROUND: Eccentric rotational acetabular osteotomy is performed to prevent osteoarthritis caused by developmental dysplasia of the hip (DDH). To achieve sufficient acetabular coverage, understanding the characteristics of acetabular coverage in DDH is necessary. However, the features of acetabular coverage in males with DDH remain unclear. We thought that the differences in acetabular coverage between females and males might be associated with the differences in pelvic morphology between the sexes. QUESTIONS/PURPOSES: (1) What are the differences in the acetabular coverage between females and males with DDH? (2) What are the differences in the rotations of the ilium and ischium between females and males with DDH? (3) What is the relationship between the rotation of the ilium and ischium and the acetabular coverage at each height in females and males with DDH? METHODS: Between 2016 and 2023, 114 patients (138 hips) underwent eccentric rotational acetabular osteotomy at our hospital. We excluded patients with Tönnis Grade 2 or higher, a lateral center-edge angle of 25º or more, and deformities of the pelvis or femur, resulting in 100 patients (122 hips) being included. For female patients (98 hips), the median (range) age was 40 years (10 to 58), and for the male patients (24 hips), it was 31 years (14 to 53). We used all patients' preoperative AP radiographs and CT data. The crossover sign, posterior wall sign, and pelvic width index were evaluated in AP radiographs. The rotation of the innominate bone in the axial plane was evaluated at two different heights, specifically at the slice passing through the anterior superior iliac spine and the slice through the pubic symphysis and ischial spine in CT data. Furthermore, we evaluated the anterior and posterior acetabular sector angles. Comparisons of variables related to innominate bone measurements and acetabular coverage measurements between females and males in each patient were performed. The correlations between pelvic morphology measurements and acetabular coverage were evaluated separately for females and males, and the results were subsequently compared to identify any sex-specific differences. For continuous variables, we used the Student t-test; for binary variables, we used the Fisher exact test. A p value less than 0.05 was considered statistically significant. RESULTS: In the evaluation of AP radiographs, an indicator of acetabular retroversion-the crossover sign-showed no differences between the sexes, whereas the posterior wall sign (females 46% [45 of 98] hips versus males 75% [18 of 24] hips, OR 3.50 [95% confidence interval (CI) 1.20 to 11.71]; p = 0.01) and pelvic width index less than 56% (females 1% [1 of 98] versus males 17% [4 of 24], OR 18.71 [95% CI 1.74 to 958.90]; p = 0.005) occurred more frequently in males than in females. There were no differences in the iliac rotation parameters, but the ischium showed more external rotation in males (females 30° ± 2° versus males 24° ± 1°; p < 0.001). Regarding acetabular coverage, no differences between females and males were observed in the anterior acetabular sector angles. In contrast, males showed smaller values than females for the posterior acetabular sector angles (85° ± 9° versus 91° ± 7°; p = 0.002). In females, a correlation was observed between iliac rotation and acetabular sector angles (anterior acetabular sector angles: r = -0.35 [95% CI -0.05 to 0.16]; p < 0.001, posterior acetabular sector angles: r = 0.42 [95% CI 0.24 to 0.57]; p < 0.001). Similarly, ischial rotation showed a correlation with both acetabular sector angles (anterior acetabular sector angles: r = -0.34 [95% CI -0.51 to -0.15]; p < 0.001 and posterior acetabular sector angles: r = 0.45 [95% CI 0.27 to 0.59]; p < 0.001). Thus, in females, we observed that external iliac rotation and ischial internal rotation correlated with increased anterior acetabular coverage and reduced posterior coverage. In contrast, although acetabular coverage in males showed a correlation with iliac rotation (anterior acetabular sector angles: r = -0.55 [95% CI -0.78 to -0.18]; p = 0.006 and posterior acetabular sector angles: r = 0.74 [95% CI 0.48 to 0.88]; p < 0.001), no correlation was observed with ischial rotation. CONCLUSION: In males, acetabular retroversion occurs more commonly than in females and is attributed to their reduced posterior acetabular coverage. In females, an increase in the posterior acetabular coverage was correlated with the external rotation angle of the ischium, whereas in males, no correlation was found between ischial rotation and posterior acetabular coverage. In treating males with DDH via eccentric rotational acetabular osteotomy, it is essential to adjust bone fragments to prevent inadequate posterior acetabular coverage. Future studies might need to investigate the differences in acetabular coverage between males and females in various limb positions and consider the direction of bone fragment rotation. CLINICAL RELEVANCE: Our findings suggest that males with DDH exhibit acetabular retroversion more frequently than females, which is attributed to the reduced posterior acetabular coverage observed in males. The smaller posterior acetabular coverage in males might be related to differences in ischial morphology between sexes. During eccentric rotational acetabular osteotomy for males with DDH, adequately rotating acetabular bone fragments might be beneficial to compensate for deficient posterior acetabular coverage.
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Acetábulo , Osteotomía , Humanos , Masculino , Femenino , Acetábulo/cirugía , Acetábulo/diagnóstico por imagen , Adulto , Osteotomía/métodos , Adulto Joven , Adolescente , Factores Sexuales , Persona de Mediana Edad , Niño , Displasia del Desarrollo de la Cadera/cirugía , Displasia del Desarrollo de la Cadera/diagnóstico por imagen , Estudios Retrospectivos , Articulación de la Cadera/cirugía , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/fisiopatología , Ilion/diagnóstico por imagen , Ilion/cirugía , Isquion/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
Advanced glycation end products (AGEs) have been reported to be associated with osteoporosis, aging, sarcopenia, and frailty. This study aimed to investigate the association AGEs with locomotive syndrome (LS). Participants were Japanese individuals aged 39 years or older who participated in the Yakumo Study (n=230). AGEs were measured by skin autofluorescence (SAF) using an AGE reader. We investigated SAF values for each locomotive stage. Multivariate logistic regression models were used to calculate the odds ratios of LS-associated factors. The relationships between SAF and physical performance and bone mineral density (BMD) were investigated. A receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value of SAF for predicting LS. SAF values tended to increase correspondingly with LS severity. SAF was an independently explanatory factor for LS (odds ratio 2.70; 95% confidence interval [CI] 1.040-6.990). SAF was positively correlated with the 10-m walking speed, The Timed Up and Go test results, and was negatively correlated with BMD. ROC curve represented by SAF for the presence or absence of LS risk had an area under the curve of 0.648 (95% CI: 0.571-0.726). High SAF values were identified as an independent risk factor for LS. AGEs could be a potential screening tool for people for LS.
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Productos Finales de Glicación Avanzada , Vida Independiente , Piel , Humanos , Productos Finales de Glicación Avanzada/metabolismo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Piel/metabolismo , Densidad Ósea/fisiología , Imagen Óptica/métodos , Síndrome , Adulto , Curva ROC , Anciano de 80 o más Años , JapónRESUMEN
The outcome of total hip arthroplasty (THA) in patients with end-stage arthritis of the hip is associated with preoperative physical status. This study was performed to examine the relationship between the preoperative severity of sarcopenia and clinical outcomes after THA. This retrospective cohort study was performed among 306 consecutive patients (mean age: 63.7 ± 12.9 years, 222 women) undergoing THA at a university hospital. The severity of sarcopenia was determined based on the skeletal muscle mass index (SMI), handgrip strength, and gait speed according to the criteria of the Asian Working Group for Sarcopenia 2019. The severe sarcopenia prevalence rate was 10.6%. Severe sarcopenia was significantly associated with the risk of delayed functional recovery (adjusted odds ratio, 2.82; 95% confidence interval, 1.03-7.72; p = 0.043) compared with the non-sarcopenia group after adjusting for pre-existing risk factors, including preoperative hip function and physical activity. The addition of SMI, handgrip strength, and gait speed to the model for risk of functional recovery delay significantly increased the area under the receiver operating characteristic curve (p = 0.038). Severe sarcopenia was significantly associated with poorer hip function and patient-reported outcomes at 6 months after surgery compared with the non-sarcopenia group. Severe sarcopenia was adversely associated with postoperative clinical outcomes in patients undergoing THA.
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Artroplastia de Reemplazo de Cadera , Fuerza de la Mano , Recuperación de la Función , Sarcopenia , Índice de Severidad de la Enfermedad , Humanos , Sarcopenia/epidemiología , Sarcopenia/complicaciones , Artroplastia de Reemplazo de Cadera/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Músculo Esquelético/fisiopatología , Periodo Preoperatorio , Factores de Riesgo , Velocidad al CaminarRESUMEN
INTRODUCTION: Early surgery for hip fracture, within 48 hours of hospital admission, is effective in reducing mortality. However, the average preoperative waiting time for hip fractures in Japan is 4.5 days and the 1-year mortality rate after a hip fracture is 10% in Japan. This study aimed to investigate whether early surgery, within 48 hours, could reduce the 1-year mortality rate in patients with hip fractures in Japan. METHODS: This cohort study involved 402 consecutive patients with hip fractures who underwent surgical treatment between January 2013 and September 2019. The exclusion criteria were an age of <60 years and in-hospital injury. A total of 389 patients were included in this study. The patients were divided into two groups: those who underwent early surgery within 48 hours of admission (early group) and those who di not undergo early surgery (delayed group). We compared patient characteristics and treatment outcomes between the 2 groups. RESULTS: A comparison of patient characteristics revealed that the early group had lower hemoglobin levels (P=0.046), lower C-reactive protein levels (P = 0.031), lower numbers of patients with weekend hospitalization, lower numbers of patients with a history of using medications that may cause bleeding (P < 0.01), and who received general anaesthesia (P < 0.01). However, there were no significant differences with regard to the other variables between the 2 groups. A treatment outcome analysis showed that the early group had shorter waiting times for surgery (P < 0.01) and shorter stays in acute-care wards (P < 0.01). However there were no differences in the total hospital stay, Barthel index at discharge, home discharge rates, in-hospital mortality rates, and 1-year mortality. CONCLUSION: Our findings indicate that early surgery did not reduce the 1-year mortality rate in older patients with hip fractures in Japan.
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Fracturas de Cadera , Tiempo de Tratamiento , Humanos , Fracturas de Cadera/cirugía , Fracturas de Cadera/mortalidad , Masculino , Femenino , Japón/epidemiología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Factores de Tiempo , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Evidence is accumulating that osteal macrophages, in addition to bone-resorbing osteoclasts and bone-forming osteoblasts, participate vitally in bone remodeling process. Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodeling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We have reported that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in MC3T3-E1 osteoblast-like cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase are involved in the OPG synthesis. The present study aims to investigate the effect of OSM on the synthesis of OPG stimulated by BMP-4 in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells. Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK was affected by OSM. On the other hand, the phosphorylation of p70 S6 kinase stimulated by BMP-4 was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblast-like cells.
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Proteína Morfogenética Ósea 4 , Oncostatina M , Osteoblastos , Osteoprotegerina , Proteínas Quinasas S6 Ribosómicas 70-kDa , Animales , Ratones , Oncostatina M/farmacología , Oncostatina M/metabolismo , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Osteoprotegerina/metabolismo , Osteoprotegerina/biosíntesis , Proteína Morfogenética Ósea 4/metabolismo , Proteína Morfogenética Ósea 4/farmacología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Línea CelularRESUMEN
Flavin photocatalysis were utilised for an aerobic oxidative reaction between arylamines and o-phenylenediamine. This metal-free reaction proceeded in methanol under visible light irradiation and consumed only atmospheric molecular oxygen, providing a novel eco-friendly method for the synthesis of benzimidazoles.
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AIM: Advanced glycation end-products (AGEs) are irreversibly and heterogeneously formed compounds during the non-enzymatic modification of macromolecules, such as proteins. Aging and lifestyle habits, such as high-fat and high-protein diets, and smoking, promote AGEs accumulation. This study aimed to investigate the relationship between fall risk and AGEs in community-dwelling older adults. METHODS: This cross-sectional study included patients from the 2022 Yakumo Study who were evaluated for fall risk index 5-items version, locomotive syndrome stage and AGEs. AGEs were evaluated using Skin autofluorescence (SAF) measured by the AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). We divided the participants into two groups according to the presence or absence of fall risk (fall risk index 5-items version ≥6 or not), and investigated the factors associated with fall risk. RESULTS: The fall risk group had a higher age and SAF, and a higher proportion of locomotive syndrome stage >2 than the without fall risk group in patients aged ≥65 years (P < 0.01). The multivariate logistic regression analysis after adjustment of age, sex and body mass index showed that locomotive syndrome stage ≥2 and SAF were independent associators of fall risk in older adults (odds ratio 3.26, P < 0.01, odds ratio 2.96, P < 0.05, respectively). The optimal cutoff value of the SAF for fall risk was 2.4 (area under the curve 0.631; 95% CI 0.53-0.733; sensitivity 0.415; specificity 0.814; P < 0.05). CONCLUSION: The accumulation of AGEs in skin tissues can be used to screen for fall risk comprehensively. Geriatr Gerontol Int 2024; 24: 517-522.
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Accidentes por Caídas , Productos Finales de Glicación Avanzada , Vida Independiente , Humanos , Productos Finales de Glicación Avanzada/metabolismo , Masculino , Anciano , Femenino , Estudios Transversales , Accidentes por Caídas/estadística & datos numéricos , Anciano de 80 o más Años , Factores de Riesgo , Japón/epidemiología , Medición de Riesgo , Evaluación Geriátrica/métodos , Piel/metabolismoRESUMEN
PURPOSE: Muscle quality is more important than muscle mass for assessing physical function. Computed tomography (CT) is used to evaluate intramuscular fatty infiltration. The mid-thigh quadriceps CT attenuation values (CTV) expressed in Hounsfield units (HU) negatively correlate with physical function. Patients with hip osteoarthritis (HOA) have lower extremity muscle atrophy, including decreased cross-sectional area (CSA), CTV, and muscle strength. Using preoperative CT images, we investigated the association between mid-thigh quadriceps CSA, CTV, and postoperative outcomes in patients with HOA. METHODS: This study included 62 patients who had unilateral HOA (62 hips) and underwent total hip arthroplasty (THA). We investigated the association between preoperative and postoperative Japanese Orthopaedic Association (JOA) hip scores, 12-item Short Form survey (SF-12), mid-thigh quadriceps CSA, and CTV. RESULTS: The mean age was 64.7 ± 10.1 years, with 15 men (24.2%), and the mean body mass index was 24.3 ± 4.3 kg/m2. Secondary HOA was present in 79.0% of patients. The mean CSA and CTV of the mid-thigh quadriceps on the operative side were 38.8 ± 9.8 cm2 and 40.3 ± 7.8 HU, respectively. Multiple regression analyses adjusted for age and sex showed that preoperative mid-thigh quadriceps CSA was not associated with preoperative and postoperative JOA hip scores or SF-12. The preoperative mid-thigh quadriceps CTV was associated with the postoperative JOA hip score in the gait ability domain and SF-12 in the physical component summary domain. CONCLUSION: Preoperative muscle quality is associated with postoperative outcomes in patients who have HOA regardless of age and sex.
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Artroplastia de Reemplazo de Cadera , Osteoartritis de la Cadera , Músculo Cuádriceps , Humanos , Masculino , Artroplastia de Reemplazo de Cadera/métodos , Femenino , Persona de Mediana Edad , Músculo Cuádriceps/diagnóstico por imagen , Músculo Cuádriceps/fisiopatología , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/fisiopatología , Estudios Retrospectivos , Anciano , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Muslo , Fuerza Muscular/fisiología , Atrofia Muscular/etiología , Atrofia Muscular/diagnóstico por imagenRESUMEN
BACKGROUND: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. METHODS: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. RESULTS: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O+ area). In consistency with in-vitro findings, VdrMPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. CONCLUSIONS: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.
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Células Madre Mesenquimatosas , Músculo Esquelético , Receptores de Calcitriol , Transducción de Señal , Vitamina D , Animales , Ratones , Vitamina D/metabolismo , Vitamina D/farmacología , Células Madre Mesenquimatosas/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Masculino , Receptores de Calcitriol/metabolismo , Tejido Adiposo/metabolismo , Adipogénesis , Modelos Animales de Enfermedad , Diferenciación CelularRESUMEN
Background: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin® (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate the molecular mechanisms underlying the effects of NTP on the inflammatory response, we evaluated gene expression in the scar tissues and dorsal root ganglions (DRGs) of mice administered NTP and control mice. Methods and results: Mice injected with saline or NTP were used as controls; other mice were subjected to surgery on the left hind paw to induce painful scar formation, and then injected with saline or NTP. Hind paw pain was evaluated by measuring the threshold for mechanical stimulation using the von Frey test. The paw withdrawal threshold gradually returned to pre-operative levels over 4 weeks post-operation; NTP-treated mice showed a significantly shortened recovery time of approximately 3 weeks, suggesting that NTP exerted an analgesic effect in this mouse model. Total RNA was extracted from the scarred hind paw tissues and DRGs were collected 1 week post-operation for a microarray analysis. Gene set enrichment analysis revealed that the expression of some gene sets related to inflammatory responses was activated or inhibited following surgery and NTP administration. Quantitative real-time reverse transcription-polymerase chain reaction analysis results for several genes were consistent with the microarray results. Conclusion: The administration of NTP to the hind paws of mice with painful scar formation following surgery diminished nociceptive pain and reduced the inflammatory response. NTP inhibited the expression of some genes involved in the response to surgery-induced inflammation. Therefore, NTP is a potential therapeutic option for painful scar associated with chronic pain.
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Dolor Crónico , Cicatriz , Modelos Animales de Enfermedad , Inflamación , Polisacáridos , Animales , Masculino , Ratones , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/etiología , Cicatriz/tratamiento farmacológico , Cicatriz/patología , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/tratamiento farmacológico , Polisacáridos/farmacologíaRESUMEN
It is often difficult to achieve adequate bone coverage of the cup in total hip arthroplasty in cases of severe developmental dysplasia of the hip (DDH). This study aimed to evaluate the relationship between subluxation percentage of Crowe classification and cup center-edge (cup-CE) angle to investigate whether subluxation percentage according to the Crowe classification is a useful indicator for cementless cup placement. Cementless cup placement was simulated in 77 women with DDH in 91 hips (Crowe I, 35 hips; Crowe II, 35 hips; and Crowe III, 21 hips) using computed tomography-based computer simulation software. The cups were placed at the anatomic hip center (AHC) and 10-mm high hip center (HHC). The relationship between the subluxation percentage and cup-CE angle was evaluated using Spearman's rank correlation coefficient. In addition, the cutoff values for the subluxation percentage that satisfied a cup-CE angle ≥0° were determined using the receiving operating characteristic curve. The cup-CE angle was negatively correlated with the subluxation percentage in both AHC and 10-mm HHC (correlation coefficient ρ = -0.542 [p < 0.01] and -0.704 [p < 0.01], respectively). The cutoff values for subluxation percentage that satisfied a cup-CE angle ≥0° were 56.1% and 73.6% for AHC and 10-mm HHC, respectively. Cementless cup placement in AHC is difficult in cases with the subluxation percentage ≥56.1%, and HHC reconstruction or femoral structural autograft technique should be considered as an alternative. Moreover, placement at 10 mm above AHC is difficult in cases with subluxation percentage ≥73.6%.
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Artroplastia de Reemplazo de Cadera , Simulación por Computador , Osteoartritis de la Cadera , Humanos , Femenino , Artroplastia de Reemplazo de Cadera/métodos , Persona de Mediana Edad , Anciano , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/diagnóstico por imagen , Adulto , Prótesis de Cadera , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Akt plays diverse roles in humans. It is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), which is caused by insulin resistance. Akt also plays a vital role in human platelet activation. Furthermore, the hippocampus is closely associated with memory and learning, and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia. AIM: To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients. METHODS: Platelet-rich plasma (PRP) was prepared from the venous blood of patients with T2DM or age-matched controls. The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt, p38 mitogen-activated protein (MAP) kinase and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Phosphorylation levels were quantified by densitometric analysis. Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging, which proposes the Z-score as a parameter that reflects hippocampal volume. RESULTS: The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects, whereas the levels of phosphorylated Akt corrected with GAPDH were not. However, this relationship was not observed in the control patients. CONCLUSION: These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients. Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.
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BACKGROUND: Intraoperative femoral fractures are more common in cementless bipolar hip arthroplasty (BHA) for displaced femoral neck fractures than they are in cemented BHA and remain one of the major concerns. This study aimed to investigate the risk factors for intraoperative femoral fractures in cementless BHA. METHODS: The study included 1,392 patients who underwent cementless BHA for displaced femoral neck fractures from January 2015 to December 2019 in 14 hospitals of the Trauma Research Group. They were divided into two groups according to the presence or absence of intraoperative femoral fractures, and factors associated with intraoperative fractures were statistically examined. RESULTS: Forty (2.9 %) intraoperative and 28 (2.0 %) postoperative, totally 68 (4.9 %) femoral fractures occurred. The mean age of the patients, presence of opposite-side proximal femoral fracture, approach, and cementless stem design were significantly different between the two groups (P < 0.05). The logistic regression analysis model showed that a fully HA-coated stem (odds ratio, 4.12; 95 % confidence interval, 1.43-11.9) was an independent factor associated with intraoperative femoral fractures. CONCLUSION: This study investigated the risk factors associated with intraoperative fractures and showed that fully HA-coated stems were an independent factor associated with intraoperative femoral fractures. Surgeons should be cautious in the early stages of introducing fully HA-coated stems.
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BACKGROUND: In some cases, patients feel a perceived leg length discrepancy (P-LLD) despite no radiographic leg length discrepancy (R-LLD) after total hip arthroplasty (THA). We aimed to investigate the rate of postoperative P-LLD and the factors that cause postoperative P-LLD. METHODS: A retrospective study was conducted on 100 patients with R-LLD ≤5 mm after THA. Patients were classified into two groups based on P-LLD post-THA: group P (with P-LLD) and group E (without P-LLD). Relevant data on the general characteristics and radiological findings between the two groups were compared. RESULTS: We observed that 25 & 75% of patients belonged to group P and group E, respectively, with no significant difference in patient background. Postoperative Japanese Orthopedic Association (JOA) classification of pain and activities of daily living scores were significantly lower in group P than in group E (37.2 ± 3.9 vs. 39.1 ± 2.2, respectively; P = 0.013, and 16.2 ± 4.2 vs. 18.2 ± 2.2, respectively; P = 0.011). The preoperative pelvic oblique angle (POA) was significantly larger in group P than in group E (3.3 ± 2.3° vs. -0.2 ± 2.1°; respectively; P < 0.01). The pelvis tilted toward the surgical side was significantly higher in group P than in group E(88% vs 57%; respectively; P = 0.013). The preoperative C7 coronal vertical axis (C7 CVA) was significantly larger in group P than in group E (6.7 ± 14.7 mm vs. -0.2 ± 10.3 mm; respectively; P = 0.028). Multivariate logistic analysis revealed that preoperative POA (OR, 3.71; 95% CI: 1.86-8.12; P < 0.01) and the pelvis tilted toward the surgical side (OR, 4.14; 95% CI: 2.07-9.71; P = 0.022) were independent risk factors for P-LLD after THA. CONCLUSION: Even though there was no postoperative R-LLD, 25% of patients had P-LLD. A large preoperative POA and the pelvis tilted toward the surgical side were independent risk factors for P-LLD after THA.
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Artroplastia de Reemplazo de Cadera , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios Retrospectivos , Pierna/cirugía , Actividades Cotidianas , Diferencia de Longitud de las Piernas/diagnóstico por imagen , Diferencia de Longitud de las Piernas/etiología , Diferencia de Longitud de las Piernas/cirugía , Pelvis/cirugía , PercepciónRESUMEN
BACKGROUND: Collapse cessation is of utmost importance following a long period of collapse due to osteonecrosis of the femoral head (ONFH). This study investigated the relationship between collapse cessation and the extent of the necrotic regions of ONFH. METHODS: Overall, 74 patients who had symptomatic ONFH (collapse < 3 mm) at the first visit with a minimum follow-up of 3 years were included in this study. Patients were categorized based on collapse progression or cessation into the progression and stable groups. The extent of the antero-posterior (AP) and medio-lateral necrotic regions between the groups was assessed using sagittal and coronal sections of T1-magnetic resonance imaging. Additionally, the most effective cutoff value was determined from the receiving operating characteristic curve where collapse cessation could be obtained, while the survival rates were determined with collapse progression as the endpoints were evaluated. RESULTS: Overall, 45 and 29 patients were in the progression and stable groups, respectively. The AP and medio-lateral necrotic regions were significantly different (P < .01 and P < .01, respectively) between the progression and stable groups. A cutoff value of 62.1% of the AP necrotic regions was determined from the receiving operating characteristic curve analysis. The 5-year survival rates with collapse progression as the endpoints were 5.4 and 77.8% in the AP necrotic regions of ≥62.1 and <62.1%, respectively (P < .01). CONCLUSIONS: Cases with AP necrotic regions of ≤62.1% can be expected to have collapse cessation, which could be a useful index for ONFH treatment strategies. LEVEL OF EVIDENCE: Level IV.
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Necrosis de la Cabeza Femoral , Cabeza Femoral , Humanos , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Necrosis de la Cabeza Femoral/cirugía , Necrosis de la Cabeza Femoral/complicaciones , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodosRESUMEN
PURPOSE: Patients with dysplastic hip osteo arthritis (DHOA) often have a spinopelvic imbalance, and they are more likely to experience falls. This study aimed to evaluate the risk factors for falls in patients with DHOA, including spinopelvic parameters. METHODS: In this cross-sectional study, a total of 103 patients with DHOA were included from 2019 to 2021. Fall risk was evaluated using the Fall Risk Index 5 items version (FRI-5). Demographics, functional outcomes, and spinopelvic parameters were compared between the high-risk group (FRI-5 ≥ 6) and the low-risk group (FRI-5 < 6). Multivariate analysis was performed using factors with significant differences in univariate analysis. RESULTS: High-risk and low-risk groups comprised 54 and 49 patients, respectively. Females were significantly more common in the high-risk group than in the low-risk group. The Harris Hip Score was significantly lower in the high-risk group than in the low-risk group (p = 0.02). Pelvic incidence, tilt, and obliquity were significantly higher in the high-risk group than in the low-risk group (p < 0.01). In multivariate analysis, female sex (odds ratio [OR]: 3.76, 95% confidence interval [CI]: 1.11-12.64, p = 0.03), pelvic obliquity (OR: 1.36, 95% CI: 1.09-1.71, p < 0.01), and Harris hip score (OR: 0.96, 95% CI: 0.93-0.99, p = 0.02) were identified as risk factors. CONCLUSION: Female sex, pelvic obliquity, and low Harris hip score were associated with an increased risk of falls among patients with DHOA.
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Artroplastia de Reemplazo de Cadera , Enfermedades Óseas , Osteoartritis de la Cadera , Humanos , Femenino , Osteoartritis de la Cadera/complicaciones , Osteoartritis de la Cadera/epidemiología , Estudios Transversales , Pelvis , Factores de RiesgoRESUMEN
The synthesis of a chiral supramolecular organogel via the hierarchical helical self-assembly of optically active riboflavin and melamine derivatives is described herein. Owing to the photocatalysis of riboflavin and the supramolecular chirality induced in the helically stacked riboflavin/melamine complex, the gel is observed to act as a light-stimulated chiral sensor of optically active alcohols by detecting the change in color from yellow to green. The gel also served as an efficient chiral adsorbent, enabling optical resolution of a racemic compound with high chiral recognition ability.