111In-Pentetreotide Uptake Due to COVID-19 Vaccination.

ABSTRACT: A 72-year-old woman was referred for whole-body 111In-pentetreotide scintigraphy with SPECT/CT. There was increased uptake of lymphadenopathy in the left axilla and left deltoid muscle. The patient's history revealed that the patient received the first dose of the COVID-19 vaccine 3 days before the 111In-pentetreotide scintigraphy with SPECT/CT. This case demonstrates that the COVID-19 vaccine can cause 111In-pentetreotide uptake in the lymph nodes and the deltoid muscle.

Recommendations for the analysis of gene expression data to identify intrinsic differences between similar tissues.

Identifying genes involved in functional differences between similar tissues from expression profiles is challenging, because the expected differences in expression levels are small. To exemplify this challenge, we studied the expression profiles of two skeletal muscles, deltoid and biceps, in healthy individuals. We provide a series of guides and recommendations for the analysis of this type of studies. These include how to account for batch effects and inter-individual differences to optimize the detection of gene signatures associated with tissue function. We provide guidance on the selection of optimal settings for constructing gene co-expression networks through parameter sweeps of settings and calculation of the overlap with an established knowledge network. Our main recommendation is to use a combination of the data-driven approaches, such as differential gene expression analysis and gene co-expression network analysis, and hypothesis-driven approaches, such as gene set connectivity analysis. Accordingly, we detected differences in metabolic gene expression between deltoid and biceps that were supported by both data- and hypothesis-driven approaches. Finally, we provide a bioinformatic framework that support the biological interpretation of expression profiles from related tissues from this combination of approaches, which is available at github.com/tabbassidaloii/AnalysisFrameworkSimilarTissues.

X-linked Emery-Dreifuss muscular dystrophy manifesting with adult onset axial weakness, camptocormia, and minimal joint contractures.

Emery-Dreifuss muscular dystrophy is an early-onset, slowly progressive myopathy characterized by the development of multiple contractures, muscle weakness and cardiac dysfunction. We present here the case of a 65-year-old male patient with a 20 year history of slowly progressive camptocormia, bradycardia and shortness of breath. Examination showed severe spine extensor and neck flexor muscle weakness with slight upper limb proximal weakness. Cardiologic assessment revealed slow atrial fibrillation. Whole body MRI demonstrated adipose substitution of the paravertebral, limb girdle and peroneal muscles as well as the tongue. Emerin immunohistochemistry on patient muscle biopsy revealed the absence of nuclear envelope labeling confirmed by Western Blot. Genetic analysis showed a hemizygous duplication of 5 bases in exon 6 of the EMD, emerin, gene on the X chromosome. This is an unusual presentation of X-linked Emery-Dreifuss muscular dystrophy with adult onset, predominant axial muscles involvement and minimal joint contractures. Diagnosis was prompted by the analysis of emerin on muscle biopsy.

Effect of Fatty Acid-Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis.

BACKGROUND: A rotator cuff tear (RCT) induces fatty acid-binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. PURPOSE: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. RESULTS: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. CONCLUSION: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. CLINICAL RELEVANCE: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.

Muscle ion transporters and antioxidative proteins have different adaptive potential in arm than in leg skeletal muscle with exercise training.

It was evaluated whether upper-body compared to lower-body musculature exhibits a different phenotype in relation to capacity for handling reactive oxygen species (ROS), H+, La-, Na+, K+ and also whether it differs in adaptive potential to exercise training. Eighty-three sedentary premenopausal women aged 45 ± 6 years (mean ± SD) were randomized into a high-intensity intermittent swimming group (HIS, n = 21), a moderate-intensity swimming group (MOS, n = 21), a soccer group (SOC, n = 21), or a control group (CON, n = 20). Intervention groups completed three weekly training sessions for 15 weeks, and pre- and postintervention biopsies were obtained from deltoideus and vastus lateralis muscle. Before training, monocarboxylate transporter 4 (MCT4), Na+/K+ pump α2, and superoxide dismutase 2 (SOD2) expressions were lower (P < 0.05) in m deltoideus than in m vastus lateralis, whereas deltoid had higher (P < 0.05) Na+/H+ exchanger 1 (NHE1) expression. As a result of training, Na+/K+ pump α2 isoform expression was elevated only in deltoideus muscle, while upregulation (P < 0.05) of the α1 and ß1 subunits, phospholemman (FXYD1), NHE1, and superoxide dismutase 1 expression occurred exclusively in vastus lateralis muscle. The increased (P < 0.05) expression of MCT4 and SOD2 in deltoid muscle after HIS and vastus lateralis muscle after SOC were similar. In conclusion, arm musculature displays lower basal ROS, La-, K+ handling capability but higher Na+-dependent H+ extrusion capacity than leg musculature. Training-induced changes in the ion-transporting and antioxidant proteins clearly differed between muscle groups.

Elevated IL-4 and IFN-γ Levels in Muscle Tissue of Patients with Dermatomyositis.

BACKGROUND/AIM: To investigate the contribution of muscle tissue-derived cytokines in dermatomyositis (DM). MATERIALS AND METHODS: Muscle homogenates were prepared from deltoid muscle biopsy specimens of 10 patients with DM and eight controls with no pathological signs of myopathy. Interleukin (IL)-4, interferon (IFN)-γ and IL-17 levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis. Muscle strength grades were recorded. RESULTS: Patients with DM showed significantly elevated muscle tissue IL-4 and IFN-γ levels, whereas IL-17 levels were comparable between patients with DM and controls. Immunoblotting studies confirmed ELISA results. In DM muscle specimens, IL-4 and IFN-γ levels were positively correlated, while no correlation was observed between IL-17 and the other two cytokines. Moreover, IL-4 and IFN-γ levels were significantly negative correlated with muscle strength grades for the deltoid muscle. CONCLUSION: Our results confirm the involvement of T helper (Th) 1-type and Th2-type immunity in DM pathogenesis. Muscle tissue appears to contribute to muscle weakness in DM by producing inflammatory cytokines.

Cyclic movement frequency is associated with muscle typology in athletes.

There is a continuing research interest in the muscle fiber type composition (MFTC) of athletes. Recently, muscle carnosine quantification by proton magnetic resonance spectroscopy (1 H-MRS) was developed as a new non-invasive method to estimate MFTC. This cross-sectional study aims to better understand estimated MFTC in relation to (a) different disciplines within one sport; (b) cyclic sport exercise characteristics; (c) within-athlete variability; and (d) athlete level. A total of 111 elite athletes (74 runners, 7 triathletes, 11 swimmers, 14 cyclists and 5 kayakers) and 188 controls were recruited to measure muscle carnosine in gastrocnemius and deltoid muscle by 1 H-MRS. Within sport disciplines, athletes were divided into subgroups (sprint-, intermediate-, and endurance-type). The controls were used as reference population to allow expression of the athletes' data as Z-scores. Within different sports, endurance-type athletes systematically showed the lowest Z-score compared to sprint-type athletes, with intermediate-type athletes always situated in between. Across the different sports disciplines, carnosine content showed the strongest significant correlation with cyclic movement frequency (R = 0.86, P = 0.001). Both within and between different cyclic sports, estimated MFTC was divergent between sprint- and endurance-type athletes. Cyclic movement frequency, rather than exercise duration came out as the most determining factor for the optimal estimated MFTC in elite athletes.

Statins Trigger Mitochondrial Reactive Oxygen Species-Induced Apoptosis in Glycolytic Skeletal Muscle.

AIMS: Although statins are the most widely used cholesterol-lowering agents, they are associated with a variety of muscle complaints. The goal of this study was to characterize the effects of statins on the mitochondrial apoptosis pathway induced by mitochondrial oxidative stress in skeletal muscle using human muscle biopsies as well as in vivo and in vitro models. RESULTS: Statins increased mitochondrial H2O2 production, the Bax/Bcl-2 ratio, and TUNEL staining in deltoid biopsies of patients with statin-associated myopathy. Furthermore, atorvastatin treatment for 2 weeks at 10 mg/kg/day in rats increased H2O2 accumulation and mRNA levels and immunostaining of the Bax/Bcl-2 ratio, as well as TUNEL staining and caspase 3 cleavage in glycolytic (plantaris) skeletal muscle, but not in oxidative (soleus) skeletal muscle, which has a high antioxidative capacity. Atorvastatin also decreased the GSH/GSSG ratio, but only in glycolytic skeletal muscle. Cotreatment with the antioxidant, quercetin, at 25 mg/kg/day abolished these effects in plantaris. An in vitro study with L6 myoblasts directly demonstrated the link between mitochondrial oxidative stress following atorvastatin exposure and activation of the mitochondrial apoptosis signaling pathway. INNOVATION: Treatment with atorvastatin is associated with mitochondrial oxidative stress, which activates apoptosis and contributes to myopathy. Glycolytic muscles are more sensitive to atorvastatin than oxidative muscles, which may be due to the higher antioxidative capacity in oxidative muscles. CONCLUSION: There is a link between statin-induced mitochondrial oxidative stress and activation of the mitochondrial apoptosis signaling pathway in glycolytic skeletal muscle, which may be associated with statin-associated myopathy.

Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and Caucasians in the arctic winter.

During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation.

Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator-cuff muscle.

The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)-based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alpha-bungarotoxin staining, and the γ:ε subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU+ (activated) Pax7+ satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher γ:ε subunit ratio than deltoid (P = 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO-donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome.

Paliperidone Palmitate Long-Acting Injectable Given Intramuscularly in the Deltoid Versus the Gluteal Muscle: Are They Therapeutically Equivalent?

Paliperidone palmitate long-acting injectable is a second-generation antipsychotic indicated for the treatment of schizophrenia. According to the product monograph, the monthly maintenance dose of paliperidone palmitate can be given in either the deltoid or gluteal muscle. Unfortunately, many clinicians may misinterpret these directions to mean that these intramuscular sites are interchangeable, and thus therapeutically equivalent. Currently, the literature on this topic is sparse, but the published pharmacokinetic studies and Food and Drug Administration submission data on paliperidone palmitate show discrepancies in the elimination half-life, peak plasma concentration, and absorption rate that are dependent on the site of injection. The degree of shifts in pharmacokinetic parameters suggests that paliperidone palmitate injections via the deltoid and gluteal muscle are not bioequivalent and therefore are not therapeutically equivalent. Thus, using the same maintenance dosing regimen at both sites or switching between sites of injection may result in unforeseen consequences in patient outcomes.

Conserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G.

Limb-girdle muscular dystrophy 2G is caused by mutations in the TCAP gene that encodes for telethonin. Here we describe a 49 year-old male patient of Indian descent presenting a classical LGMD phenotype. He had normal motor milestones but became noticeably slower in his early teens and was wheelchair bound by age 44. The muscle biopsy showed myopathic features and absence of labeling with an antibody to the C-terminal portion of telethonin. Sequence analysis of the TCAP gene revealed a novel homozygous mutation in exon 2, predicted to generate a truncated protein of 81 amino acids. Interestingly, an antibody for the full-length protein showed labeling on sections and a single band of ~10 kDa on Western blot. The truncated protein co-localized with filamin C at the Z-line. Our findings indicate that mutant telethonin can be incorporated into the sarcomere and that other LGMD2G patients with retention of telethonin expression may exist.

Regional oxygen saturation index (rSO2) in brachioradialis and deltoid muscle. Correlation and prognosis in patients with respiratory sepsis.

OBJECTIVE: To compare oxygen saturation index (rSO2) obtained simultaneously in two different brachial muscles. DESIGN: Prospective and observational study. SETTING: Intensive care unit. PATIENTS: Critically ill patients with community-acquired pneumonia. INTERVENTIONS: Two probes of NIRS device (INVOS 5100) were simultaneously placed on the brachioradialis (BR) and deltoid (D) muscles. VARIABLES: rSO2 measurements were recorded at baseline (ICU admission) and at 24h. Demographic and clinical variables were registered. Pearson's correlation coefficient was used to assess the association between continuous variables. The consistency of the correlation was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plot. The predictive value of the rSO2 for mortality was calculated by ROC curve. RESULTS: Nineteen patients were included with an ICU mortality of 21.1%. The rSO2 values at baseline and at 24h were significantly higher in D than in BR muscle. Values obtained simultaneously in both limbs showed a strong correlation and adequate consistency: BR (r=0.95; p<0.001; ICC=0.94; 95% CI: 0.90-0.96; p<0.001), D (r=0.88; p=0.01; ICC=0.88; 95% CI: 0.80-0.90; p>0.001) but a wide limit of agreement. Non-survivors had rSO2 values significantly lower than survivors at all times of the study. No patient with rSO2 >60% in BR died, and only 17.6% died with an rSO2 value >60% in D. Both muscles showed consistent discriminatory power for mortality. CONCLUSION: Both BR and D muscles were appropriate for measuring rSO2.

Comparison of muscle activity in the empty-can and full-can testing positions using 18 F-FDG PET/CT.

BACKGROUND: There has been much controversy over specific tests for diagnosis of supraspinatus tendon tear. The aim of this study was to evaluate the metabolic activity of the deltoid and rotator cuff muscles while maintaining the full-can and empty-can testing positions using 2-deoxy-2-[18 F]fluoro-D-glucose (18 F-FDG) positron emission tomography (PET)/computed tomography (CT). METHODS: Ten healthy volunteers without shoulder pain or diabetes mellitus participated in this study. Following FDG injection, both arms were maintained in either the empty-can or full-can position for 10 min. PET/CT was performed 40 min after injection. Maximum standardized uptake values (SUVs) were measured in the deltoid and rotator cuff muscles on axial PET images. RESULTS: The middle deltoid exhibited the most significant increase in muscle activity at both testing positions. Additionally, a significant increase in muscle activity was observed in the middle deltoid compared with the supraspinatus (P < 0.05) in the empty-can testing position. SUVs of the middle deltoid, supraspinatus, and subscapularis showed a significant increase in the empty-can testing position compared with the full-can testing position (P < 0.05). CONCLUSIONS: Significantly increased activity of the supraspinatus in conjunction with the middle deltoid and subscapularis after empty-can testing may result in decreased specificity of the empty-can test in detecting isolated supraspinatus activity. The full-can test, however, may be used to test the function of the supraspinatus with the least amount of surrounding middle deltoid and subscapularis activity.

Muscle gene expression is a marker of amyotrophic lateral sclerosis severity.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset degenerative disease characterized by the loss of upper and lower motor neurons leading to progressive muscle atrophy and paralysis. The lack of molecular markers of the progression of disease is detrimental to clinical practice and therapeutic trials. OBJECTIVE: This study was designed to identify gene expression changes in skeletal muscle that could reliably define the degree of disease severity. METHODS: Gene expression profiles were obtained from the deltoid muscles of ALS patients and healthy subjects. Changes in differentially expressed genes were compared to the status of deltoid muscle disability, as determined by manual muscle testing, electrophysiology and the degree of myofiber atrophy. Functionally related genes were grouped by annotation analysis, and deltoid muscle injury was predicted using binary tree classifiers. RESULTS: Two sets of 25 and 70 transcripts appeared differentially regulated exclusively in early and advanced states of deltoid muscle impairment, respectively. The expression of another set of 198 transcripts correlated with a composite score of muscle injury combining manual muscle testing and histological examination. From the totality of these expression changes, 155 transcripts distinguished advanced from early deltoid muscle impairment with 80% sensitivity and 100% specificity. Nine of these transcripts, known also to be regulated in ALS mouse and surgically denervated muscle, predicted the advanced disease status with 100% sensitivity and specificity. CONCLUSION: We provide robust gene expression changes that can be of practical use when monitoring ALS status and the effects of disease-modifying drugs.

Direct oxymetric peripheral tissue perfusion monitoring during open heart surgery with the use of cardiopulmonary bypass: preliminary experience.

BACKGROUND: Regional hypoperfusion has been associated with the development of postoperative organ dysfunction in cardiac surgery involving cardiopulmonary bypass (CPB). Direct tissue oxymetry is a potentially new method for monitoring the quality of the peripheral tissue perfusion during CPB. The aim of this study was to assess the effects of CPB in skeletal muscle oxygenation when measured in the deltoid muscle by direct oxymetry during perioperative period. METHOD: Seven patients underwent on-pump coronary artery bypass grafting. Direct oxymetry was performed by an optical cathether introduced into the deltoid muscle. Continuous measurement was made during the surgical procedure and the postoperative period. Mean arterial blood pressure, blood flow during CPB, laboratory markers of tissue hypoperfusion, blood gases and body temperature were also recorded. RESULTS: Interstitial muscle tissue oxygen tension (pO(2)) decreased after the introduction to anaesthesia and, more significantly, during CPB. After the disconnection from CPB at the end of the operation, the pO(2) returned to pre-anaesthetic values. During the first hours after admission of the patients to the intensive care unit, the pO(2) progressively decreased, reached a minimum value after four hours, and increased slowly thereafter. There was a significant correlation of pO(2) with mean arterial blood pressure and blood flow during that time. CONCLUSION: The result of this first measurement seems to demonstrate that the standard technique of conducting cardiopulmonary bypass produces low muscle oxygen tension and, thus, little perfusion of skeletal muscle. The data also indicate that both high mean arterial blood pressure and high flow are necessary during CPB to ensure skeletal muscle perfusion. The investigation is continuing.