3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes.

Age-related atrophy of skeletal muscle, is characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern how exercise serves to promote healthy muscle aging are unclear. Mitochondrial aging is associated with decreased mitochondrial capacity, so we sought to investigate how aging affects mitochondrial structure and potential age-related regulators. Specifically, the three-dimensional (3D) mitochondrial structure associated with morphological changes in skeletal muscle during aging requires further elucidation. We hypothesized that aging causes structural remodeling of mitochondrial 3D architecture representative of dysfunction, and this effect is mitigated by exercise. We used serial block-face scanning electron microscopy to image human skeletal tissue samples, followed by manual contour tracing using Amira software for 3D reconstruction and subsequent analysis of mitochondria. We then applied a rigorous in vitro and in vivo exercise regimen during aging. Across 5 human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria we less spherical and more complex, indicating age-related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age-related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved as Marf, the MFN2 ortholog in Drosophila, knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age-related structural changes in mitochondria and further suggest that exercise may mitigate age-related structural decline through modulation of mitofusin 2.

The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.

The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health.

Anthropometric study of the knee in patients with osteoarthritis: intraoperative measurement versus magnetic resonance imaging.

OBJECTIVE: To compare intraoperative measurements of the knee with those obtained by magnetic resonance imaging, in order to validate the latter method for use in anthropometric studies. MATERIALS AND METHODS: We studied 20 knees in 20 patients with osteoarthritis, all of whom underwent total arthroplasty between August and December of 2013. We took six measurements in the distal femur and two in the proximal tibia. Using the information system of the institution, we made the measurements on magnetic resonance imaging scans that had been obtained in the axial plane. Intraoperative measurements were obtained using a caliper, after the initial cuts made during the arthroplasty. The anatomical parameters determined by magnetic resonance imaging were the same as those determined by intraoperative measurement. The intraclass correlation coefficient was used in order to assess the level of agreement in anthropometric measurements of the knee performed by magnetic resonance imaging and by intraoperative measurement. RESULTS: Statistical analysis revealed a highly significant correlation between the knee anthropometric parameters of the knee determined by intraoperative measurement and those determined by magnetic resonance imaging. CONCLUSION: The dimensions of osteoarthritic knees measured by magnetic resonance imaging were similar to those measured intraoperatively. Therefore, magnetic resonance imaging can be considered a reliable method for use in large-scale anthropometric studies that will allow the available implants to be adapted and improved.

OBJETIVO: Comparar a mensuração do joelho realizada por meio de ressonância magnética com a medida obtida intraoperatoriamente, a fim de validar o método para estudos antropométricos. MATERIAIS E MÉTODOS: Foram estudados 20 joelhos em 20 pacientes portadores de osteoartrite submetidos a artroplastia total, entre agosto e dezembro de 2013. Realizaram-se seis medidas no fêmur distal e duas na tíbia proximal. As mensurações nas imagens foram feitas no plano axial, por meio do sistema informatizado da instituição. As mensurações intraoperatórias foram obtidas utilizando-se um paquímetro, após os cortes iniciais da artroplastia. Os parâmetros anatômicos foram os mesmos. O coeficiente de correlação intraclasses foi utilizado para avaliar a concordância nas medidas antropométricas de joelho realizadas pela ressonância magnética e pelo paquímetro de forma intraoperatória. RESULTADOS: A análise estatística revelou que existe concordância altamente significativa entre as medidas antropométricas do joelho conseguidas por meio do uso do paquímetro intraoperatoriamente e pela ressonância magnética. CONCLUSÃO: A mensuração das dimensões dos joelhos osteoartríticos por meio de ressonância magnética apresentou-se como método semelhante à mensuração intraoperatória, sendo confiável para a realização de estudos antropométricos amplos que permitam a adequação e melhoria de implantes disponíveis.

Magnetic resonance study on the anatomical relationship between the posterior proximal region of the tibia and the popliteal artery.

OBJECTIVE: To analyze and describe the distance from the popliteal artery to three specific areas of the proximal region of the tibia, with the knee extended, by means of magnetic resonance. METHODS: Images of 100 knees of patients who underwent magnetic resonance examinations were analyzed. The location of the popliteal artery was measured in three different areas of the posterior proximal region of the tibia. The first measurement was made at the level of the knee joint (tibial plateau). The second was 9 mm distally to the tibial plateau. The third was at the level of the anterior tuberosity of the tibia (ATT). RESULTS: The distances between the popliteal artery and the tibial plateau and ATT region were significantly greater in males than in females. The distances between the popliteal artery and the regions 9 mm distally to the tibial plateau and the ATT were significantly greater in the age group over 36 years than in the group ≤36 years. CONCLUSION: Knowledge of the anatomical position of the popliteal artery, as demonstrated through magnetic resonance studies, is of great relevance in planning surgical procedures that involve the knee joint. In this manner, devastating iatrogenic injuries can be avoided, particularly in regions that are proximal to the tibial plateau and in young patients.

OBJETIVO: Analisar e descrever, com o joelho em extensão, a distância da artéria poplítea em três áreas específicas da região proximal da tíbia, por meio de ressonância magnética. MÉTODOS: Foram analisadas as imagens de 100 joelhos de pacientes submetidos a exame por ressonância magnética. A localização da artéria poplítea foi medida em três áreas distintas da região proximal posterior da tíbia. A primeira medida foi feita no nível da articulação do joelho (platô tibial). A segunda, a 9 mm distal do platô tibial. A terceira, ao nível da tuberosidade anterior da tíbia (TAT). RESULTADOS: As distâncias entre a artéria poplítea e o platô tibial e a região da TAT foram significativamente maiores no sexo masculino do que no feminino. As distâncias entre a artéria poplítea e a região 9 mm distal do platô tibial e a TAT foram significativamente maiores na faixa acima de 36 anos do que na faixa ≤ 36 anos. CONCLUSÃO: O conhecimento da posição anatômica da artéria poplítea, demonstrada por estudos de RM, é de grande relevância no planejamento de procedimentos cirúrgicos que envolvam a articulação do joelho. Com isso, podem-se evitar lesões iatrogênicas devastadoras, principalmente em regiões proximais ao platô tibial e em pacientes jovens.

Rotational assessment of distal femur and its relevance in total knee arthroplasty: analysis by magnetic resonance imaging.

OBJECTIVE: To define the distal femur rotation pattern in a Brazilian population, correlating such pattern with the one suggested by the arthroplasty instruments, and analyzing the variability of each anatomic parameter. MATERIALS AND METHODS: A series of 101 magnetic resonance imaging studies were evaluated in the period between April and June 2012. The epidemiological data collection was performed with the aid of the institution's computed imaging system, and the sample included 52 male and 49 female patients. The measurements were made in the axial plane, with subsequent correlation and triangulation with the other plans. The posterior condylar line was used as a reference for angle measurements. Subsequently, the anatomical and surgical transepicondylar axes and the anteroposterior trochlear line were specified. The angles between the reference line and the studied lines were calculated with the aid of the institution's software. RESULTS: The mean angle between the anatomical transepicondylar axis and the posterior condylar line was found to be 6.89°, ranging from 0.25° to 12°. For the surgical transepicondylar axis, the mean value was 2.89°, ranging from -2.23° (internal rotation) to 7.86°, and for the axis perpendicular to the anteroposterior trochlear line, the mean value was 4.77°, ranging from -2.09° to 12.2°. CONCLUSION: The anatomical transepicondylar angle showed mean values corresponding to the measurement observed in the Caucasian population. The utilized instruments are appropriate, but no anatomical parameter proved to be steady enough to be used in isolation.

OBJETIVO: Definir o padrão de rotação do fêmur distal em população brasileira, correlacionar esse padrão com o sugerido pelos instrumentais de artroplastia e analisar a variabilidade de cada parâmetro anatômico. MATERIAIS E MÉTODOS: Foram avaliados 101 exames de ressonância magnética no período compreendido entre abril e junho de 2012. A coleta dos dados epidemiológicos foi feita pelo sistema informatizado da instituição de imagem, sendo 52 pacientes masculinos e 49 femininos. As mensurações foram feitas no plano axial, correlacionando e triangulando com os outros planos. Utilizamos como referência para as medidas angulares a linha condilar posterior. Na sequência, especificamos o eixo transepicondilar anatômico, cirúrgico e a linha troclear anteroposterior. As angulações entre a linha de referência e as linhas estudadas foram calculadas pelo software da instituição. RESULTADOS: Foi encontrada uma média de 6,89° na aferição do eixo transepicondilar anatômico em relação à linha condilar posterior, variando de 0,25° a 12°. O eixo transepicondilar cirúrgico apresentou média de 2,89°, variando de ­2,23° (rotação interna) a 7,86°. O eixo perpendicular à linha troclear anteroposterior apresentou média de 4,77°, variando de ­2,09° a 12,2°. CONCLUSÃO: O ângulo transepicondilar cirúrgico apresentou valores médios correspondentes aos da população caucasiana. Os instrumentais estão adequados, porém nenhum parâmetro anatômico se mostrou constante o suficiente para ser usado de forma isolada.

Magnetic resonance imaging of the lumbar spine with axial loading: a review of 120 cases.

PURPOSE: To evaluate the imaging findings of patients with clinical symptoms of lower back pain who underwent magnetic resonance imaging (MRI) of the lumbar spine with axial loading. MATERIALS AND METHODS: We examined 120 patients by MRI, before and after axial loading, using a compression device that applied 50% of their body weight for a load time of 5min. The dural sac cross area (DSCA) was examined by two experienced radiologists before and after axial load, and their findings were compared. Degenerative abnormalities within and adjacent to the spinal canal were also analyzed. RESULTS: A reduction in DSCA greater than 15mm(2) after axial load was defined as significant, and was found in 81 patients (67.5%) and 138 disc spaces (38.3%). Reduction was most frequent at L4-L5 (n=55). For other disorders, a 9% increase in cases of bulging disc was seen during axial loading, and seven disc spaces showed protrusion/extrusion only after load. Facet joint synovial cysts, foraminal stenosis, and hypertrophy of the flavum ligaments showed almost no differences, pre- and post-load. CONCLUSION: For adequate evaluation of lumbar symptoms, examination should be performed with axial loading, especially in cases of suspected spinal stenosis.

Anthropometric study of the knee in patients with osteoarthritis: intraoperative measurement versus magnetic resonance imaging / Estudo antropométrico do joelho em portadores de osteoartrite: comparação da mensuração intraoperatória e por ressonância magnética

Abstract Objective: To compare intraoperative measurements of the knee with those obtained by magnetic resonance imaging, in order to validate the latter method for use in anthropometric studies. Materials and Methods: We studied 20 knees in 20 patients with osteoarthritis, all of whom underwent total arthroplasty between August and December of 2013. We took six measurements in the distal femur and two in the proximal tibia. Using the information system of the institution, we made the measurements on magnetic resonance imaging scans that had been obtained in the axial plane. Intraoperative measurements were obtained using a caliper, after the initial cuts made during the arthroplasty. The anatomical parameters determined by magnetic resonance imaging were the same as those determined by intraoperative measurement. The intraclass correlation coefficient was used in order to assess the level of agreement in anthropometric measurements of the knee performed by magnetic resonance imaging and by intraoperative measurement. Results: Statistical analysis revealed a highly significant correlation between the knee anthropometric parameters of the knee determined by intraoperative measurement and those determined by magnetic resonance imaging. Conclusion: The dimensions of osteoarthritic knees measured by magnetic resonance imaging were similar to those measured intraoperatively. Therefore, magnetic resonance imaging can be considered a reliable method for use in large-scale anthropometric studies that will allow the available implants to be adapted and improved.

Resumo Objetivo: Comparar a mensuração do joelho realizada por meio de ressonância magnética com a medida obtida intraoperatoriamente, a fim de validar o método para estudos antropométricos. Materiais e Métodos: Foram estudados 20 joelhos em 20 pacientes portadores de osteoartrite submetidos a artroplastia total, entre agosto e dezembro de 2013. Realizaram-se seis medidas no fêmur distal e duas na tíbia proximal. As mensurações nas imagens foram feitas no plano axial, por meio do sistema informatizado da instituição. As mensurações intraoperatórias foram obtidas utilizando-se um paquímetro, após os cortes iniciais da artroplastia. Os parâmetros anatômicos foram os mesmos. O coeficiente de correlação intraclasses foi utilizado para avaliar a concordância nas medidas antropométricas de joelho realizadas pela ressonância magnética e pelo paquímetro de forma intraoperatória. Resultados: A análise estatística revelou que existe concordância altamente significativa entre as medidas antropométricas do joelho conseguidas por meio do uso do paquímetro intraoperatoriamente e pela ressonância magnética. Conclusão: A mensuração das dimensões dos joelhos osteoartríticos por meio de ressonância magnética apresentou-se como método semelhante à mensuração intraoperatória, sendo confiável para a realização de estudos antropométricos amplos que permitam a adequação e melhoria de implantes disponíveis.

Estudo por ressonância magnética da relação anatômica entre a região proximal posterior da tíbia e a artéria poplítea / Magnetic resonance study on the anatomical relationship between the posterior proximal region of the tibia and the popliteal artery

Analisar e descrever, com o joelho em extensão, a distância da artéria poplítea em três áreas específicas da região proximal da tíbia, por meio de ressonância magnética. MÉTODOS: Foram analisadas as imagens de 100 joelhos de pacientes submetidos a exame por ressonância magnética. A localização da artéria poplítea foi medida em três áreas distintas da região proximal posterior da tíbia. A primeira medida foi feita no nível da articulação do joelho (platô tibial). A segunda, a 9 mm distal do platô tibial. A terceira, ao nível da tuberosidade anterior da tíbia (TAT). RESULTADOS: As distâncias entre a artéria poplítea e o platô tibial e a região da TAT foram significativamente maiores no sexo masculino do que no feminino. As distâncias entre a artéria poplítea e a região 9 mm distal do platô tibial e a TAT foram significativamente maiores na faixa acima de 36 anos do que na faixa ≤ 36 anos. CONCLUSÃO: O conhecimento da posição anatômica da artéria poplítea, demonstrada por estudos de RM, é de grande relevância no planejamento de procedimentos cirúrgicos que envolvam a articulação do joelho. Com isso, podem-se evitar lesões iatrogênicas devastadoras, principalmente em regiões proximais ao platô tibial e em pacientes jovens.

To analyze and describe the distance from the popliteal artery to three specific areas of the proximal region of the tibia, with the knee extended, by means of magnetic resonance. METHODS: Images of 100 knees of patients who underwent magnetic resonance examinations were analyzed. The location of the popliteal artery was measured in three different areas of the posterior proximal region of the tibia. The first measurement was made at the level of the knee joint (tibial plateau). The second was 9 mm distally to the tibial plateau. The third was at the level of the anterior tuberosity of the tibia (ATT). RESULTS: The distances between the popliteal artery and the tibial plateau and ATT region were significantly greater in males than in females. The distances between the popliteal artery and the regions 9 mm distally to the tibial plateau and the ATT were significantly greater in the age group over 36 years than in the group ≤36 years. CONCLUSION: Knowledge of the anatomical position of the popliteal artery, as demonstrated through magnetic resonance studies, is of great relevance in planning surgical procedures that involve the knee joint. In this manner, devastating iatrogenic injuries can be avoided, particularly in regions that are proximal to the tibial plateau and in young patients.

Rotational assessment of distal femur and its relevance in total knee arthroplasty: analysis by magnetic resonance imaging / Avaliação rotacional do fêmur distal e sua importância na artroplastia total de joelho: análise por ressonância magnética

AbstractObjective:To define the distal femur rotation pattern in a Brazilian population, correlating such pattern with the one suggested by the arthroplasty instruments, and analyzing the variability of each anatomic parameter.Materials and Methods:A series of 101 magnetic resonance imaging studies were evaluated in the period between April and June 2012. The epidemiological data collection was performed with the aid of the institution's computed imaging system, and the sample included 52 male and 49 female patients. The measurements were made in the axial plane, with subsequent correlation and triangulation with the other plans. The posterior condylar line was used as a reference for angle measurements. Subsequently, the anatomical and surgical transepicondylar axes and the anteroposterior trochlear line were specified. The angles between the reference line and the studied lines were calculated with the aid of the institution's software.Results:The mean angle between the anatomical transepicondylar axis and the posterior condylar line was found to be 6.89°, ranging from 0.25° to 12°. For the surgical transepicondylar axis, the mean value was 2.89°, ranging from –2.23° (internal rotation) to 7.86°, and for the axis perpendicular to the anteroposterior trochlear line, the mean value was 4.77°, ranging from –2.09° to 12.2°.Conclusion:The anatomical transepicondylar angle showed mean values corresponding to the measurement observed in the Caucasian population. The utilized instruments are appropriate, but no anatomical parameter proved to be steady enough to be used in isolation.

ResumoObjetivo:Definir o padrão de rotação do fêmur distal em população brasileira, correlacionar esse padrão com o sugerido pelos instrumentais de artroplastia e analisar a variabilidade de cada parâmetro anatômico.Materiais e Métodos:Foram avaliados 101 exames de ressonância magnética no período compreendido entre abril e junho de 2012. A coleta dos dados epidemiológicos foi feita pelo sistema informatizado da instituição de imagem, sendo 52 pacientes masculinos e 49 femininos. As mensurações foram feitas no plano axial, correlacionando e triangulando com os outros planos. Utilizamos como referência para as medidas angulares a linha condilar posterior. Na sequência, especificamos o eixo transepicondilar anatômico, cirúrgico e a linha troclear anteroposterior. As angulações entre a linha de referência e as linhas estudadas foram calculadas pelo software da instituição.Resultados:Foi encontrada uma média de 6,89° na aferição do eixo transepicondilar anatômico em relação à linha condilar posterior, variando de 0,25° a 12°. O eixo transepicondilar cirúrgico apresentou média de 2,89°, variando de –2,23° (rotação interna) a 7,86°. O eixo perpendicular à linha troclear anteroposterior apresentou média de 4,77°, variando de –2,09° a 12,2°.Conclusão:O ângulo transepicondilar cirúrgico apresentou valores médios correspondentes aos da população caucasiana. Os instrumentais estão adequados, porém nenhum parâmetro anatômico se mostrou constante o suficiente para ser usado de forma isolada.