Anatomical Compartments Research Articles

Exploring the amyloid degradation potential of nanoformulated carrageenan-bridging in vitro and in vivo perspectives

Amyloids, with their β-sheet-rich structure, contribute to diabetes, neurodegenerative diseases, and amyloidosis by aggregating within diverse anatomical compartments. Insulin amyloid (IA), sharing structural resemblances with amyloids linked to neurological disorders, acts as a prototype, while compounds capable of degrading these fibrils hold promise as therapeutic agents for amyloidosis intervention. In this research, liposomal nanoformulated iota carrageenan (nCG) was formulated to disrupt insulin amyloids, demonstrating about a 17–20 % higher degradation efficacy compared to conventional carrageenan through thioflavin T fluorescence, dynamic light scattering analysis, and turbidity quantification. The biocompatibility of the nCG and nCG-treated insulin amyloids was evaluated through MTT assay, live-dead cell assay on V79 cells, and hemolysis testing on human blood samples to establish their safety for use in vitro. Zebrafish embryos were utilized to assess in vivo biocompatibility, while adult zebrafish were employed to monitor the degradation capacity of IA post subcutaneous injection, with fluorescence emitted by the fish captured via IVIS. This demonstrated that the formulated nCG exhibited superior anti-amyloid efficacy compared to carrageenan alone, while both materials demonstrated biocompatibility. Furthermore, through docking simulations, an exploration was conducted into the molecular mechanisms governing the inhibition of the target protein pancreatic insulin by carrageenan.

The foregut in cystic fibrosis.

The aerodigestive organs share a kindred embryologic origin that allows for a more complete explanation as to how the foregut can remain a barrier to normalcy in people with cystic fibrosis (pwCF). The structures of the aerodigestive tract include the nasopharynx, the oropharynx, the hypopharynx, the esophagus, the stomach, as well as the supraglottic, glottic, and subglottic tubular airways (including the trachea). Additional gastrointestinal (GI) luminal/alimentary organs of the foregut include the duodenum. Extraluminal foregut structures include the liver, the gall bladder, the biliary tree, and the pancreas. There are a variety of neurologic controls within these complicated anatomic compartments to separate the transit of food and liquid from air. These structures share the same origin from the primitive foregut/mesenchyme. The vagus nerve is a critical structure that unites respiratory and digestive functions. This article comments on the interconnected nature of cystic fibrosis and the GI tract. As it relates to the foregut, this has been typically treated as simple "reflux" as the cause of worsened lung function in pwCF. That terms like gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), heartburn, and regurgitation are used interchangeably to reflect pathology further complicates matters; we offer a more physiologically accurate term called "GI-related aspiration" or "GRASP." Broadly, this term reflects that aspiration of foregut contents from the duodenum through the stomachto the esophagus, into the pharynx and the respiratory tree in pwCF. As a barrier to normalcy in pwCF, GRASP is fundamentally two disease processes-GERD and gastroparesis-that likely contribute most to the deterioration of lung disease in pwCF. In the modulator era, successful GRASP management will be critical, particularly in those post-lung transplantation (LTx), only through successful management of both GERD and gastroparesis. Standardization of clinical management algorithms for GRASP in CF-related GRASP is a key clinical and research gap preventing normalcy in pwCF; what exists nearly exclusively addresses surgical evaluations or offers guidance for the management of GI symptoms alone (with unclear parameters for respiratory disease considerations). We begin first by describing the result of GRASP damage to the lung in various stages of lung disease. This is followed by a discussion of the mechanisms by which the digestive tract can injure the lungs. We summarize what we anticipate future research directions will be to reduce the impact of GRASP as a barrier to normalcy in pwCF.

Isometric Plantarflexion Moment Prediction Based on a Compartment-Specific HD-sEMG-Driven Musculoskeletal Model.

electromyogram (EMG)-driven musculoskeletal models have been widely used to investigate human movements while existing EMG-driven models commonly neglect regional heterogeneity in anatomy and activation within a skeletal muscle. To consider neuromuscular compartment anatomy and activation, a subject- and compartment-specific EMG-driven model was developed for isometric plantarflexion moment prediction. the model was hill-type consisting of gastrocnemius medialis, gastrocnemius lateralis, and soleus around the ankle joint, and each muscle was discretised into four compartments. The moment arms of each compartment were determined using magnetic resonance imaging and the compartment activation was calculated based on high-density surface EMG signals. And the hill-type compartment parameters were tuned in a calibration process. The developed compartment-specific model and a generic EMG-driven model were examined by comparing their predicted net ankle moments with measurements obtained while subjects performed isometric plantarflexion tasks at different contraction levels. compared to the generic EMG-driven model, the isometric plantarflexion moment prediction using the compartment-specific model was more accurate at all contraction levels, with the average prediction error decreasing from average 13.81% to 10.11%. The contraction of each compartment was found to be generally non-uniform at all contraction levels. the developed compartment-specific model enabled accurate prediction of isometric plantarflexion moment and the simulation of non-uniform muscular contraction, which is more physiologically appropriate than the existing EMG-driven models. the proposed compartment-specific formulation opens new perspectives for subject-specific musculoskeletal modelling, which has great potential in understanding regional characteristics of the neuromuscular activities.

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). In this cohort study, patients (≥ 18years old) with CRC were followed for 36months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.

ScMultiome analysis identifies a single caudal hindbrain compartment in the developing zebrafish nervous system

BackgroundA key step in nervous system development involves the coordinated control of neural progenitor specification and positioning. A long-standing model for the vertebrate CNS postulates that transient anatomical compartments – known as neuromeres – function to position neural progenitors along the embryonic anteroposterior neuraxis. Such neuromeres are apparent in the embryonic hindbrain – that contains six rhombomeres with morphologically apparent boundaries – but other neuromeres lack clear morphological boundaries and have instead been defined by different criteria, such as differences in gene expression patterns and the outcomes of transplantation experiments. Accordingly, the caudal hindbrain (CHB) posterior to rhombomere (r) 6 has been variably proposed to contain from two to five ‘pseudo-rhombomeres’, but the lack of comprehensive molecular data has precluded a detailed definition of such structures.MethodsWe used single-cell Multiome analysis, which allows simultaneous characterization of gene expression and chromatin state of individual cell nuclei, to identify and characterize CHB progenitors in the developing zebrafish CNS.ResultsWe identified CHB progenitors as a transcriptionally distinct population, that also possesses a unique profile of accessible transcription factor binding motifs, relative to both r6 and the spinal cord. This CHB population can be subdivided along its dorsoventral axis based on molecular characteristics, but we do not find any molecular evidence that it contains multiple pseudo-rhombomeres. We further observe that the CHB is closely related to r6 at the earliest embryonic stages, but becomes more divergent over time, and that it is defined by a unique gene regulatory network.ConclusionsWe conclude that the early CHB represents a single neuromere compartment that cannot be molecularly subdivided into pseudo-rhombomeres and that it may share an embryonic origin with r6.

Myogenic Regulator Genes Responsible For Muscle Development in Farm Animals

Farm animals especially poultry species play important roles in meeting the worldwide demand for meat and are genetically improved to increase the efficiency of meat production. Improving muscle growth and development is crucial to meet customers' demands for high-quality meat. Myogenesis, fibrogenesis, and adipogenesis are components of fetal skeletal muscle formation. Myogenesis is controlled by a complex network of intrinsic and extrinsic components, usually divided into two or three stages and regulated by kinase-encoding genes and myogenic regulatory factor genes. The basic family of helix-loop-helix transcription factors, which includes MYF5, MYOD, myogenin, and MRF4, regulates the specification and differentiation of skeletal muscle cells throughout embryogenesis and postnatal myogenesis. With the discovery of the myogenic regulatory factor family, which includes the transcription factors MYF5, MYOD, Myogenin, and MRF4, it has become possible to determine the skeletal muscle lineage and understand the regulation of myogenic differentiation during development. These elements also play a role in determining the muscle satellite cell lineage that develops into the resident stem cell compartment in adult skeletal muscle. Although MYF5, MYOD, Myogenin and MRF4 play minor roles in mature muscle, they once again play an important role in directing satellite cell activity to regenerate skeletal muscle, linking the genetic regulation of development and regeneration myogenesis. An important step towards the goal of increasing meat yield and improving meat quality is the understanding and identification of these genes. This in-depth analysis discusses the function of myogenic regulatory factors in the specification of satellite cells, maturation and regeneration of skeletal muscle.

Long-term phase angle muscle imaging under electrical muscle stimulation (EMS) by phase angle electrical impedance tomography

Objectives. Phase angle muscle imaging has been proposed by phase angle electrical impedance tomography (ΦEIT) under electrical muscle stimulation (EMS) for long-term monitoring of muscle quality improvement, especially focusing on calf muscles. Approach. In the experiments, twenty-four subjects are randomly assigned either to three groups: control group (CG, n = 8), low voltage intensity of EMS training group (LG, n = 8), and optimal voltage intensity of EMS training group (OG, n = 8). Main results. From the experimental results, phase angle distribution images Ф are cleared reconstructed by ФEIT as four muscle compartments over five weeks experiments, which are called the M 1 muscle compartments composed of gastrocnemius muscle, M 2 muscle compartments composed of soleus muscle, M 3 muscle compartments composed of tibialis-posterior muscle, flexor digitorum longus muscle, and flexor pollicis longus muscle, and M 4 muscle compartment composed of the tibialis anterior muscle, extensor digitorum longus muscle, and peroneus longus muscle. Ф is inversely correlated with age, namely the Ф decreases with increasing age. A paired samples t-test was conducted to elucidate the statistical significance of spatial-mean phase angle in all domain <Ф>Ω and in each muscle compartment <Ф> M with reference to the conventional phase angle Ф by bioelectrical impedance analysis, muscle grey-scale G muscle by ultrasound, and maximal dynamic strength S Max by one-repetition maximum test. Significance. From the t-test results, <Ф>Ω have good correlation with Ф and S Max. In the OG, <Ф W5>Ω, Ф W5, and (S Max)W5 were significantly higher than in the first week (n = 8, p < 0.05). A significant increase in the phase angle of both M 1 and M 4 muscle compartments is observed after five weeks in LG and OG groups. Only the OG group shows a significant increase in the phase angle of M 2 muscle compartment after five weeks. However, no significant changes in the spatial-mean phase angle of M 3 compartment are observed in each group. In conclusion, ФEIT satisfactorily monitors the response of each compartment in calf muscle to long-term EMS training.

Proteomics analysis of deep fascia in acute compartment syndrome.

Acute compartment syndrome (ACS) is a syndrome in which local circulation is affected due to increased pressure within the compartment. We previously found in patients with calf fractures, the pressure of fascial compartment could be sharply reduced upon the appearance of tension blisters. Deep fascia, as the important structure for compartment, might play key role in this process. Therefore, the aim of the present study was to examine the differences in gene profile in deep fascia tissue in fracture patients of the calf with or without tension blisters, and to explore the role of fascia in pressure improvement in ACS. Patients with lower leg fracture were enrolled and divided into control group (CON group, n = 10) without tension blister, and tension blister group (TB group, n = 10). Deep fascia tissues were collected and LC-MS/MS label-free quantitative proteomics were performed. Genes involved in fascia structure and fibroblast function were further validated by Western blot. The differentially expressed proteins were found to be mainly enriched in pathways related to protein synthesis and processing, stress fiber assembly, cell-substrate adhesion, leukocyte mediated cytotoxicity, and cellular response to stress. Compared with the CON group, the expression of Peroxidasin homolog (PXDN), which promotes the function of fibroblasts, and Leukocyte differentiation antigen 74 (CD74), which enhances the proliferation of fibroblasts, were significantly upregulated (p all <0.05), while the expression of Matrix metalloproteinase-9 (MMP9), which is involved in collagen hydrolysis, and Neutrophil elastase (ELANE), which is involved in elastin hydrolysis, were significantly reduced in the TB group (p all <0.05), indicating fascia tissue underwent microenvironment reconstruction during ACS. In summary, the ACS accompanied by blisters is associated with the enhanced function and proliferation of fibroblasts and reduced hydrolysis of collagen and elastin. The adaptive alterations in the stiffness and elasticity of the deep fascia might be crucial for pressure release of ACS.

Poster 393: Recurrence Rates of Exertional Compartment Syndrome: Endoscopic Fasciotomies vs Open Fasciotomies

Objectives: Chronic Exertional Compartment Syndrome (CECS) is a debilitating condition characterized by increased pressure within myofascial compartments often during exercise. Fasciotomy of the affected compartment is the primary treatment for refractory cases, with two main techniques commonly employed: endoscopic-assisted fasciotomy and open fasciotomy. This study compared the rates of recurrence and rates of infection in endoscopic-assisted fasciotomy and open fasciotomy. Methods: This is a retrospective cohort study of all patients diagnosed with CECS at two level 1 trauma centers between January 2006-December 2019. Data related to patient demographics, follow-up, infection rate, and recurrence rate were collected from electronic medical records. Results: There were 169 patients included in the study, with 66 undergoing endoscopically-assisted fasciotomy and 103 undergoing open fasciotomy. The average patient age was 32±11 years and 29±12 years for the endoscopic and open groups, respectively. There were 37 females (56%) in endoscopic group and 62 females (60%) in the open group. The average BMI was 29±7 and 28±6 for the endoscopic and open groups, respectively. There were 10 former smokers in each group and 1 active smoker in the open group. Average follow-up was 9±10 months and 10±15 months for the endoscopic and open groups, respectively. There were no significant differences in age, sex, BMI, smoking habit, or length of follow-up between the two groups. There were 8 infections (12%) in the endoscopic group compared to 14 infections (14%) in the open group (p=0.81). There were 8 revisions (12%) in the endoscopic group compared to 4 revisions (4%) in the open group (p=0.04). Conclusions: Endoscopically-assisted fasciotomy patients demonstrated a higher recurrence rate of CECS compared to those who underwent open fasciotomy. This may be explained my increased technical demands of endoscopic procedures and incomplete release of fascial compartments. Further research and long-term follow-up studies are warranted to elucidate the underlying mechanisms and optimize treatment strategies to reduce recurrence rates and enhance patient outcomes.

Pulmonary comorbidities in people with HIV- the microbiome connection.

To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field. Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated. Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.

Tissue-Specific Quantification of Radiation-Induced Cervical Fibrosis and Correlation with Cervical Range of Motion.

Cervical fibrosis (CF) as a late consequence in patients after radiotherapy significantly impacts the long-term symptoms, functionality, and quality of life of these cancer patients due to a hardening process of different histological tissues. Modern Shear Wave Ultrasound Elastography now enables a differentiated analysis of the changes in various tissue types. In this study, tissue-specific changes in CF induced by radiation therapy in head and neck (ENT) cancer patients were quantified and correlated with cervical range of motion (CROM). 16 patients after radiation of the cervical lymphatic drainage were selected as the observation group (OG). Further, 16 people without radiation in the head and neck region were matched by gender, age, and BMI as the control group (CG). Stiffness measurements in kilopascal (kPa; 1 Pa = 1 N m-2) were performed using shear wave elastography (SWE) to assess the elasticity of muscle, fascia, and subcutaneous tissue within and surrounding the sternocleidomastoid muscle (SCM). Specific parameters of the OG were compared to the CG and correlated with functional parameters and quality of life (QoL). The OG exhibited significantly higher stiffness values (Emean, Emax, Emin) across all tissue types than the CG, suggesting a tangible effect of radiation therapy on tissue stiffness. Muscle compartment analysis revealed the most significant stiffness differences. Thickness measurements indicated changes in the muscle and skin but not in the subcutaneous tissue. CROM measurements within the OG fell within normal ranges, suggesting a possible homogenizing effect of radiation treatment on CROM variability. Strong correlations were observed between age and specific stiffness measures, particularly in the OG group, indicating a broader impact of aging or radiation therapy on physiological measures. Significant correlations between tissue stiffness and CROM were found. CF after radiotherapy occurs primarily in the muscle tissue and its fascia, with the hardening being about twice as pronounced as in the average population and becoming more pronounced with increasing age and correlates with CROM.

Muscle diffusion tensor imaging in facioscapulohumeral muscular dystrophy.

Muscle diffusion tensor imaging has not yet been explored in facioscapulohumeral muscular dystrophy (FSHD). We assessed diffusivity parameters in FSHD subjects compared with healthy controls (HCs), with regard to their ability to precede any fat replacement or edema. Fat fraction (FF), water T2 (wT2), mean, radial, axial diffusivity (MD, RD, AD), and fractional anisotropy (FA) of thigh muscles were calculated in 10 FSHD subjects and 15 HCs. All parameters were compared between FSHD and controls, also exploring their gradient along the main axis of the muscle. Diffusivity parameters were tested in a subgroup analysis as predictors of disease involvement in muscle compartments with different degrees of FF and wT2 and were also correlated with clinical severity scores. We found that MD, RD, and AD were significantly lower in FSHD subjects than in controls, whereas we failed to find a difference for FA. In contrast, we found a significant positive correlation between FF and FA and a negative correlation between MD, RD, and AD and FF. No correlation was found with wT2. In our subgroup analysis we found that muscle compartments with no significant fat replacement or edema (FF < 10% and wT2 < 41 ms) showed a reduced AD and FA compared with controls. Less involved compartments showed different diffusivity parameters than more involved compartments. Our exploratory study was able to demonstrate diffusivity parameter abnormalities even in muscles with no significant fat replacement or edema. Larger cohorts are needed to confirm these preliminary findings.

Contrast-Enhanced Magnetic Resonance Imaging Based T1 Mapping and Extracellular Volume Fractions Are Associated with Peripheral Artery Disease.

Extracellular volume fraction (ECV), measured with contrast-enhanced magnetic resonance imaging (CE-MRI), has been utilized to study myocardial fibrosis, but its role in peripheral artery disease (PAD) remains unknown. We hypothesized that T1 mapping and ECV differ between PAD patients and matched controls. A total of 37 individuals (18 PAD patients and 19 matched controls) underwent 3.0T CE-MRI. Skeletal calf muscle T1 mapping was performed before and after gadolinium contrast with a motion-corrected modified look-locker inversion recovery (MOLLI) pulse sequence. T1 values were calculated with a three-parameter Levenberg-Marquardt curve fitting algorithm. ECV and T1 maps were quantified in five calf muscle compartments (anterior [AM], lateral [LM], and deep posterior [DM] muscle groups; soleus [SM] and gastrocnemius [GM] muscles). Averaged peak blood pool T1 values were obtained from the posterior and anterior tibialis and peroneal arteries. T1 values and ECV are heterogeneous across calf muscle compartments. Native peak T1 values of the AM, LM, and DM were significantly higher in PAD patients compared to controls (all p < 0.028). ECVs of the AM and SM were significantly higher in PAD patients compared to controls (AM: 26.4% (21.2, 31.6) vs. 17.3% (10.2, 25.1), p = 0.046; SM: 22.7% (19.5, 27.8) vs. 13.8% (10.2, 19.1), p = 0.020). Native peak T1 values across all five calf muscle compartments, and ECV fractions of the anterior muscle group and the soleus muscle were significantly elevated in PAD patients compared with matched controls. Non-invasive T1 mapping and ECV quantification may be of interest for the study of PAD.

A bicaudatus sartorius muscle: a rare variant with potential clinical implications.

Sartorius muscle (SM) belongs to the thigh anterior compartment musculature. It corresponds to the longest muscle of the human body, while its variations are described rarely. The current case reports aims to describe a distal bifurcation of the SM, forming the bicaudatus SM variant. M: ETHODS: An 84-year-old male cadaver was dissected for educational and research purposes at the Department of Anatomy, National and Kapodistrian University of Athens. On the left lower limb, the SM was typically originated from the anterior superior iliac spine. After 351.22 mm length, it was bifurcated into an anterior and posterior part. Both muscular parts were contributing to the pes anserinus morphology. Femoral nerve branches were providing innervation to the variant muscle, while the saphenous nerve and vein were coursed posteriorly to the variant muscle. SM morphological variability is described quite rarely. The current case report corresponds to the bicaudatus SM variant. Accessory parts of SM could lead to compression symptoms to the femoral nerve anterior branches, as well as to the saphenous nerve.

Research progress in the anatomy and surgical approach of the parapharyngeal space

The parapharyngeal space, a complex fascial compartment within the head and neck region, encompasses crucial anatomical structures including blood vessels and nerves. Tumors occurring within this space are rare, with the majority being benign in nature. Surgical intervention remains the primary treatment modality; however, managing parapharyngeal space tumors poses significant challenges due to their intricate anatomical configuration. Conventional open surgical approaches have been associated with significant tissue damage and a high prevalence of postoperative complications. Recently, advancements in anatomical studies and surgical techniques have led to significant progress in understanding parapharyngeal space anatomy and improving surgical management. This article aims to provide a comprehensive overview of these developments.

Association of lung cancer-associated cachexia with the metastatic spread to pleura.

12095 Background: Cancer-associated cachexia (CAC), a major contributor to mortality in patients with non-small cell lung cancer (NSCLC), is characterized by alterations in body composition. Here, we explore the associations between body composition changes and the pattern of lung cancer metastatic spread. Methods: Computer tomography (CT) images from cancer diagnosis and recurrence were used to quantify subcutaneous and visceral adipose tissue (SAT, VAT) and skeletal muscle (SKM) tissue areas at the 3rd lumbar vertebrae level, using an DAFS AI-based software, Voronoi Analytics, in 101 NSCLC pts, who relapsed after surgical treatment of the primary tumor at the Medical University of Gdansk Hospital. The decrease in SKM, SAT and VAT of more than 5% or 10% at cancer relapse was compared with the pattern of cancer recurrence. Results: The median time to recurrence after primary tumor resection was 1.6 years (0.4–6.4 years). There were 38% local or regional recurrences, 59% distant recurrences, and 13% second primary lung cancers. Among the cases with distant recurrence, there were 19% brain recurrences, 22% pleural metastases, 34% lung metastases, 17% bone metastases, and 11% cases of liver relapse. More than one site of distant recurrence occurred in 51 (50%) of patients. Loss of &gt; 5% of SKM, SAT and VAT occurred in 61%, 33% and 41% respectively. Loss of &gt;5% or &gt;10% of SKM was associated with the pleural metastases at the time of cancer recurrence, ( P &lt; 0.001). Median muscle loss was –11.6% for patients with pleural relapse and –5.3 % for patients with other metastatic locations ( P &lt; 0.001). There were no significant associations between other body composition changes and the pattern of recurrences, tumor histology or age. Conclusions: NSCLC relapse to the pleura after surgical treatment of the primary tumor, appears to be associated with a decrease in the skeletal muscle compartment. This finding may inform the design of the future studies aiming to investigate molecular correlates of sarcopenia and cancer-associated cachexia.

Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis

Cerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring the neoplastic processes of the central nervous system. We applied a lung cancer-specific sequencing panel (CAPP-Seq) to 81 CSF, blood, and tissue samples from 24 lung cancer patients who underwent lumbar puncture (LP) for suspected leptomeningeal disease (LMD). A subset of the cohort (N = 12) participated in a prospective trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment. CSF-tDNA variant allele fractions (VAFs) were significantly higher than plasma circulating tumor DNA (ctDNA) VAFs (median CSF-tDNA, 32.7%; median plasma ctDNA, 1.8%; P < 0.0001). Concentrations of tumor DNA in CSF and plasma were positively correlated (Spearman’s ρ, 0.45; P = 0.03). For LMD diagnosis, cytology was 81.8% sensitive and CSF-tDNA was 91.7% sensitive. CSF-tDNA was also strongly prognostic for overall survival (HR = 7.1; P = 0.02). Among patients with progression on targeted therapy, resistance mutations, such as EGFR T790M and MET amplification, were common in peripheral blood but were rare in time-matched CSF, indicating differences in resistance mechanisms based on the anatomic compartment. In the osimertinib cohort, patients with CNS progression had increased CSF-tDNA VAFs at follow-up LP. Post-osimertinib CSF-tDNA VAF was strongly prognostic for CNS progression (HR = 6.2, P = 0.009). Detection of CSF-tDNA in lung cancer patients with suspected LMD is feasible and may have clinical utility. CSF-tDNA improves the sensitivity of LMD diagnosis, enables improved prognostication, and drives therapeutic strategies that account for spatial heterogeneity in resistance mechanisms.

Retraction: Clonogenic, myogenic progenitors expressing MCAM/CD146 are incorporated as adventitial reticular cells in the microvascular compartment of human post-natal skeletal muscle.

Retraction: Clonogenic, myogenic progenitors expressing MCAM/CD146 are incorporated as adventitial reticular cells in the microvascular compartment of human post-natal skeletal muscle.

Heterogeneous distribution of mitochondria and succinate dehydrogenase activity in human airway smooth muscle cells

AbstractSuccinate dehydrogenase (SDH) is a key mitochondrial enzyme involved in the tricarboxylic acid cycle, where it facilitates the oxidation of succinate to fumarate, and is coupled to the reduction of ubiquinone in the electron transport chain as Complex II. Previously, we developed a confocal‐based quantitative histochemical technique to determine the maximum velocity of the SDH reaction (SDHmax) in single cells and observed that SDHmax corresponds with mitochondrial volume density. In addition, mitochondrial volume and motility varied within different compartments of human airway smooth muscle (hASM) cells. Therefore, we hypothesize that the SDH activity varies relative to the intracellular mitochondrial volume within hASM cells. Using 3D confocal imaging of labeled mitochondria and a concentric shell method for analysis, we quantified mitochondrial volume density, mitochondrial complexity index, and SDHmax relative to the distance from the nuclear membrane. The mitochondria within individual hASM cells were more filamentous in the immediate perinuclear region and were more fragmented in the distal parts of the cell. Within each shell, SDHmax also corresponded to mitochondrial volume density, where both peaked in the perinuclear region and decreased in more distal parts of the cell. Additionally, when normalized to mitochondrial volume, SDHmax was lower in the perinuclear region when compared to the distal parts of the cell. In summary, our results demonstrate that SDHmax measures differences in SDH activity within different cellular compartments. Importantly, our data indicate that mitochondria within individual cells are morphologically heterogeneous, and their distribution varies substantially within different cellular compartments, with distinct functional properties.

Diagnostics of acute compartment syndrome : Current gold standard and the state of science of noninvasive assessment methods

Acute compartment syndrome (ACS) is defined by a disorder of the microcirculation due to a persistent pathological pressure increase within amuscle compartment. The ischemia of the tissue leads to an initially reversible functional impairment and finally irreversible damage of the musculature, nerves and other structures. Based on the understanding of the pathophysiology, the current diagnostic concepts and treatment using the so-called dermatofasciotomy of the affected muscle compartments can be derived. In addition to the suspicion of a possible ACS based on the medical history of the patient, the findings of the clinical examination are decisive. This review article gives a summary of all the essential aspects of the diagnostics. In clinically uncertain cases and for monitoring, an objectification of the findings using instrument-based techniques is increasingly required. Nowadays, invasive needle pressure measurement is available; however, due to limited reliability, specificity and sensitivity, these measurements only represent an aid to decision guidance supporting or advising against the indications for dermatofasciotomy. The increasing demands on making a certain diagnosis and justification of a surgical intervention from a legal point of view, substantiate the numerous scientific efforts to develop noninvasive instrument-based diagnostics. These methods are based either on detection of increasing intracompartmental pressure or decreasing perfusion pressure and microcirculation. The various measurement principles are summarized in a lucid form.