Muscle Sites Research Articles

Regional Differences of Mechanical Properties in a Biceps Brachii Following Eccentric Exercise

PURPOSE: This study aimed to examine the effects of eccentric exercise (ECC) on the indices of mechanical properties together with markers of exercise-induced muscle damage (EIMD) in different sites of the biceps brachii (BB) muscle.METHODS: ECC using an elbow joint was performed in 13 non-trained, college men. Global symptoms of EIMD were identified through changes in muscle soreness and serum creatine kinase (CK) activity, including muscle function following ECC. To evaluate regional EIMD, muscle swelling and tenderness as well as muscular echo intensity were measured at distal (4 cm above the elbow joint) and middle (30% of the distance from the antecubital crease to the acromion) sites within the BB muscle. A handheld myotonometer was used to estimate changes in mechanical properties, that is, oscillation frequency (F), dynamic stiffness (S), and relaxation time (R), of BB muscles after ECC.RESULTS: A significant difference in the major markers of EIMD, such as muscle soreness and serum CK activity, along with parameters of muscle function, was observed after ECC compared to baseline. Although all indirect markers of regional muscle damage demonstrated meaningful differences between before and after ECC, no statistically significant interaction between the distal and middle sites was observed in any of the markers. After ECC, both distal and middle sites showed significant changes in F, S, and R, but no statistical differences in changes in muscle mechanical properties were observed between localized muscle sites within BB muscles.CONCLUSIONS: Changes in mechanical properties, including regional muscle damage, seem to be uniformly influenced by different anatomical locations within the BB muscle, such as elbow flexors, following ECC.

Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss.

Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. Estimates indicate that ~250,000 fractures occur in the US alone that involve VML. Currently, there is no active treatment to fully recover or repair muscle loss in VML patients. The health economics burden due to VML is rapidly increasing around the world. Immunologists, developmental biologists, and muscle pathophysiologists are exploring both immune responses and biomaterials to meet this challenging situation. The inflammatory response in muscle injury involves a non-specific inflammatory response at the injured site that is coordination between the immune system, especially macrophages and muscle. The potential role of biomaterials in the regenerative process of skeletal muscle injury is currently an important topic. To this end, cell therapy holds great promise for the regeneration of damaged muscle following VML. However, the delivery of cells into the injured muscle site poses a major challenge as it might cause an adverse immune response or inflammation. To overcome this obstacle, in recent years various biomaterials with diverse physical and chemical nature have been developed and verified for the treatment of various muscle injuries. These biomaterials, with desired tunable physicochemical properties, can be used in combination with stem cells and growth factors to repair VML. In the current review, we focus on how various immune cells, in conjunction with biomaterials, can be used to promote muscle regeneration and, most importantly, suppress VML pathology.

A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury.

Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury. The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation. To activate lower-limb muscles precisely by epidural spinal cord stimulation, we proposed a high-density, flexible electrode array. We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord, which was established by a transection method. For evaluating the effect of stimulation, the evoked potentials were recorded from bilateral lower-limb muscles, including the vastus lateralis, semitendinosus, tibialis anterior, and medial gastrocnemius. To determine the appropriate stimulation sites and parameters of the lower muscles, the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation. In the vastus lateralis and medial gastrocnemius, these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment, respectively. The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles. The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius. Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array. They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury. This study was approved by the Animal Research Committee of Southeast University, China (approval No. 20190720001) on July 20, 2019.

Wrist, but Not Back, Isometric Contraction Induced Widespread Hypoalgesia in Healthy Participants.

Objective: Exercise may reduce pain sensitivity. This phenomenon called exercise-induced hypoalgesia is observed in different types of exercises and involves the activation of endogenous pain modulation systems. Although the effect of limb exercise on pain sensitivity has often been tested, few studies explored the impact of back exercises that are often used to treat low back pain. The main objective is to measure the effect of back-muscle exercise on pain sensitivity and compare it to the effect of a limb-muscle exercise.Methods: Twenty-three participants who were pain-free performed a 4-min wrist flexion isometric contraction followed by a 4-min low back extension, separated by a 20-min break. Pressure pain thresholds were tested at two low back (S1 spinous process, lumbar erector spinae muscle) and two wrist (capitate bone, wrist flexor muscles) sites before and after each exercise. For each exercise, sites were considered as remote or local in relation to the muscles contracted during the exercise. An independent sample of 11 participants was recruited to confirm the influence of low back extension on pain sensitivity.Results: Wrist exercise induced a larger increase in pain sensitivity than back exercise at the remote site. Only wrist exercise induced a hypoalgesia effect at both the local and the remote sites. Back exercise induced a similar effect in the independent sample.Conclusions: This study showed that back and wrist exercises induced a distinct effect on pain sensitivity in participants who were pain-free. The wrist exercise induced a systemic reduction in pain sensitivity (locally and remotely), whereas the back exercise did not. This differential effect may be present because wrist exercise induced most fatigue compared with the back exercise.

Atropine Induced Psychosis in Organophosphate Insecticide Poisoning and it's Management: A case series

Atropine is an established antidote in organophosphorus poisoning. It is an anticholinergic that inhibits the muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites including secretory glands, smooth muscle, and CNS sites. In the literature, the cases of atropine intoxication are not uncommon. We report a case series of five cases of atropine induced psychotic disorder in patients, who manifested with delirium, hallucinations, nervousness, drowsiness, weakness, irrelevant talk, flushing along with tachycardia, and non-reactive dilated pupils suggesting possible anti-cholinergic abuse. The patients reported at the Department of Medicine-Unit II, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, from January to June 2019. The patients were managed symptomatically by titrating down the atropine's dose, administration of benzodiazepine, and antipsychotics.

Ingested Foreign Bodies and Toxic Materials: Who Needs to be Scoped and When?

1. Yasemin Cagil, MD* 2. Jenna Diaz, MD† 3. Seth Iskowitz, MD‡ 4. Alisa J. Muniz Crim, MD§ 1. *Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Lucile Packard Children’s Hospital Stanford, Palo Alto, CA 2. †Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Washington University School of Medicine in St Louis, St Louis, MO 3. ‡Division of Pediatric Gastroenterology, Hepatology, and Nutrition, C.S. Mott Children’s Hospital Michigan Medicine, Ann Arbor, MI 4. §Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nicklaus Children’s Hospital, Miami, FL Providers should be able to identify the signs and symptoms of foreign body and toxic material ingestion in children, select the proper diagnostic tests needed to confirm the diagnosis, and describe adequate treatment modalities for the described ingestions. After completing this article, readers should be able to: 1. Understand the common types of foreign body and toxic material ingestions. 2. Recognize the presenting symptoms of the described ingestions. 3. Recognize which patients warrant emergency endoscopic intervention. 4. Recognize which patients warrant nonemergency endoscopic intervention. 5. Recognize which patients warrant noninvasive medical management. 6. Review the role of prevention. Foreign body and toxic substance ingestions are a common reason for families to seek emergency care. Often, the pediatric patient is unable to describe the nature of the ingestion and/or the timing of the event. This can pose significant barriers to both caregivers and the medical team. Coins, button batteries, magnets, pointed and/or large objects, food, absorptive substances, alcohol, acidic and alkaline substances, detergent pods, and hydrocarbons are all frequently reported ingestions. Each ingested object or substance requires an individualized approach to management. The most common site for foreign bodies to become entrapped is in the proximal esophagus at the site of the cricopharyngeus muscle. Other common locations include the midesophagus, at the site of compression from the aortic arch, and at the lower esophageal sphincter. Most foreign bodies that are ingested by children pass spontaneously without complications; however, endoscopic removal may be necessary in some situations. Parameters that must be considered regarding the need for endoscopic removal of ingested foreign bodies include the child’s age, weight, clinical presentation, time since ingestion, type and size of the foreign body, location in the gastrointestinal tract, and underlying intestinal abnormalities. This section describes the most commonly ingested foreign bodies and their management. (1) ### Coins Coins remain the most commonly ingested …

Antimuscarinic Medications for Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a disease of airway obstruction.1 A major component of therapy for the management of COPD includes bronchodilators, such as muscarinic receptor antagonists, also known as anticholinergic agents.1 These medications work at the parasympathetic sites in bronchial smooth muscle via the inhibition of acetylcholine causing bronchodilation.1 Antimuscarinic drugs for COPD management include short-acting and long-acting muscarinic receptor antagonists (SAMAs and LAMAs, respectively).

The Effect of Tooth Loss on Craniofacial Morphology

The morphology of the craniofacial skeleton is known to be responsive to changing biomechanical loads produced by feeding. Edentulism, or tooth loss, has previously been shown to have an impact on the structure of the craniofacial bones, particularly the alveolar bone and palate, as well as on the material properties of the cortical bone. However, it is less clear what effect tooth loss has on the masticatory muscles and their bony attachment sites. In this study, we use geometric morphometrics on human skulls to compare the shape of the mandible and facial skeleton in edentulous and dentate individuals. Following from previous work, we expect that edentulous individuals will exhibit decreased alveolar bone height in both the mandible and maxilla. We further hypothesize that edentulous individuals will display a recession of bone at the insertion sites of the masticatory muscles, namely the zygomatic arch and the mandibular ramus. CT scans of individuals greater than 50 years of age (n=40) were obtained from the New Mexico Decedent Imaging Database (NMDID). Individuals with no teeth were sorted into the edentulous group, while individuals with more than 22 of 36 teeth were sorted into the functionally dentate. 3D Slicer software was used to generate 3D models, and 3D fixed and sliding landmarks were placed along the mandible, maxilla, zygomatic arch, palate, and orbit. Principal component analysis (PCA) and Procrustes ANOVAs were performed separately on the Procrustes-aligned coordinate data for the crania and mandibles. We identified significant differences in facial and mandibular shape between groups. In both cases, differences were largely driven by resorption along the alveolus. Variation in the morphology of edentulous individuals suggests that the time since tooth loss and behavioral factors, such as denture wearing, may impact the degree of alveolar resorption. Interestingly, edentulous individuals tended to have relatively smaller coronoid processes and posteriorly extended mandibular angles. This suggests that tooth loss may result in greater relative atrophy of the temporalis muscle, a jaw elevator/retractor, compared to the masseter muscle, another jaw elevator which is involved in resisting gravity and positional jaw closure. Further studies are needed to investigate the impact of tooth loss on muscle morphology to confirm this. These additive effects between bone resorption and muscle atrophy likely explain the altered facial morphology demonstrated by edentulous populations.

Oxygen Uptake and Near Infrared Spectroscopy Responses during Heavy Intensity Pseudorandom Binary Sequence Exercise

Activities of daily living are characterized by continuous changes in exercise intensity and duration resulting in many abrupt changes in metabolic demand. The ability to readily meet these demands is described by the rate of adaptation in oxygen uptake measured at either the mouth (VO2p) or at the site of active muscle. Many studies have used a single step transition to assess this rate of adaptation. However, a continually changing exercise, such as a pseudorandom binary sequence (PRBS) protocol, provides more transition phases to analyze. We examined the VO2p and microvascular oxygenation responses using near infrared spectroscopy (NIRS) during PRBS exercise. Five healthy males (30 ± 6 yrs, 83.4 ± 20.9 kg, VO2pk, 38.9 ± 5.9 mL/kg/min; mean ± SD) completed a ramp exercise to fatigue for the determination of the lactate threshold (LT) and peak VO2p (VO2pk). Each bout of PRBS exercise transitioned from a baseline of 20 W to a WR corresponding to either 90% of LT (MOD, 100 ± 7 W)) or to a WR at 40% of the difference between LT and VO2pk (HVY, 173 ± 13 W). The PRBS exercise consisted of 30 units of 15 s that alternated between BSL and the higher WR in a pseudorandom pattern; the pattern was repeated 3 times. VO2p was measured breath-by-breath using a metabolic cart and interpolated to 1 s intervals. For each subject and WR, the 3 repetitions for each trial were ensembled averaged yielding a single 450 s response. Changes in hemoglobin oxygenation (deoxy-[Hb+Mb]) and total hemoglobin concentration ([THC]) were measured from the vastus lateralis (VL) using frequency-domain NIRS. Data were collected at 1 Hz and ensembled averaged to yield a single 450 s response. VO2p and deoxy-[Hb+Mb] responses were transformed into the frequency domain and analyzed using standard approaches and the mean-normalized gain (MNG). The harmonic amplitudes (Amph) for VO2p/WR were lower (p<0.05) during HVY at 0.0067 Hz (Mod, 56.9 ± 13.0 %; HVY, 49.3 ± 6.8 %), 0.011 Hz (Mod, 37.6 ± 17.0 %, HVY: 25.8 ± 5.7 %) and 0.013 Hz (Mod, 33.2 ± 12.8 %; HVY, 15.8 ± 10.2 %). The Amph for deoxy-[Hb+Mb]/WR were lower (p<0.05) for VO­2p/WR in HVY compared to MOD (Mod, 39.5 ± 6.0 %; HVY, 30.2 ± 3.9 %). MNG was also lower (p<0.05) for deoxy-[Hb+Mb]/WR in HVY compared to MOD (Mod, 77.4 ± 26.6 %; HVY, 47.3 ± 10.0 %). The VO2p and deoxy-[Hb+Mb] responses from a PRBS trial represent the responses to individual sinusoidal inputs at each frequency tested. The normalized Amph and MNG measured in the current study described the temporal dynamics of the variables of interest (i.e., VO2p and deoxy-[Hb+Mb]). The results of the current study showed a significant decrease in both normalized Amph and MNG for VO2p and deoxy-[Hb+Mb] suggesting that exercise performed above the LT results in a slowing of both the VO2p and microvascular deoxy-[Hb+Mb] responses. These findings are consistent with previous studies demonstrating a slowing of VO2p above the LT. Compared to studies using a single step protocol, responses to PRBS protocols include many transition periods to identify potential control mechanisms that are more discernable during non-steady state exercise.

Detection of insulins in postmortem tissues: an optimized workflow based on immunopurification and LC-MS/HRMS detection.

Diabetes is a worldwide disease in perpetual expansion. Type 1 and sometimes type 2 diabetic patients require daily human insulin (HI) or analog administration. Easy access to insulins for insulin-treated diabetics, their relatives, and medical professionals can enable abuse for suicidal or homicidal purpose. However, demonstrating insulin overdose in postmortem blood is challenging. Tissue analyses are contributive, as insulins can accumulate before death or undergo only limited degradation. The present study describes an assay for HI and synthetic analogs (lispro, aspart, glulisine, detemir and degludec, glargine and its main metabolite (M1)) in liver, kidney, muscle, and injection site samples. It is based on a 5-step sample preparation (reduction of tissue sample size, homogenization, extraction, concentration, and immunopurification) associated with liquid chromatography coupled to high-resolution mass spectrometry (LC-MS/HRMS). Selectivity and limit of detection (LOD) for all target analogs were assessed in the above matrices. LOD was determined at 25ng/g for HI and for analogs except detemir and degludec, where LOD was 50ng/g in kidney and injection site samples and 80ng/g in the liver and muscle. The method was applied to13 forensic cases in which insulin use was suspected.

Sympathectomy decreases pain behaviors and nerve regeneration by downregulating monocyte chemokine CCL2 in dorsal root ganglia in the rat tibial nerve crush model.

Peripheral nerve regeneration is associated with pain in several preclinical models of neuropathic pain. Some neuropathic pain conditions and preclinical neuropathic pain behaviors are improved by sympathetic blockade. In this study, we examined the effect of a localized "microsympathectomy," ie, cutting the gray rami containing sympathetic postganglionic axons where they enter the L4 and L5 spinal nerves, which is more analogous to clinically used sympathetic blockade compared with chemical or surgical sympathectomy. We also examined manipulations of CCL2 (monocyte chemoattractant protein 1), a key player in both regeneration and pain. We used rat tibial nerve crush as a neuropathic pain model in which peripheral nerve regeneration can occur successfully. CCL2 in the sensory ganglia was increased by tibial nerve crush and reduced by microsympathectomy. Microsympathectomy and localized siRNA-mediated knockdown of CCL2 in the lumbar dorsal root ganglion had very similar effects: partial improvement of mechanical hypersensitivity and guarding behavior, reduction of regeneration markers growth-associated protein 43 and activating transcription factor 3, and reduction of macrophage density in the sensory ganglia and regenerating nerve. Microsympathectomy reduced functional regeneration as measured by myelinated action potential propagation through the injury site and denervation-induced atrophy of the tibial-innervated gastrocnemius muscle at day 10. Microsympathectomy plus CCL2 knockdown had behavioral effects similar to microsympathectomy alone. The results show that local sympathetic effects on neuropathic pain may be mediated in a large part by the effects on expression of CCL2, which in turn regulates the regeneration process.

Caenorhabditis elegans junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin.

The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole Caenorhabditis elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 colocalizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68 RyR calcium channel, and is required for animal movement. In neurons, JPH-1 colocalizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) in the soma, and is present near presynaptic release sites. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-2 have antagonistic roles in neuromuscular synaptic transmission. Additionally, we find an unexpected cell nonautonomous effect of jph-1 in axon regrowth after injury. Genetic double mutant analysis suggests that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and with unc-68 for animal health and development. Finally, we show that jph-1 regulates the colocalization of EGL-19 and UNC-68 and that unc-68 is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.

Proteomics analysis to investigate the effect of oxidized protein on meat color and water holding capacity in Tan mutton under low temperature storage

This study aimed to investigate the effects of oxidized proteins on meat color and water holding capacity of Tan mutton stored at low temperatures and the correlation between oxidized proteins and meat quality. Compared with the fresh control group, a total of 1089 proteins were identified as shared proteins with different oxidation sites (DOSPs) in Tan mutton from three low temperature groups (−2, −18 and 4 °C). The number of oxidation sites in Tan mutton muscle stored at −2 °C was much higher than those at −18 and 4 °C. There were also differences in the degree and site of protein oxidation between different storage groups. Pearson's correlation analysis between 275 DOSPs and quality traits of the tan mutton muscle stored at low temperatures showed that 19 DOSPs were correlated closely with color (L*, a* and b*) and water holding (CeL, CL and DL). Among them, several proteins might be potential markers for color, and some proteins are good candidate predictors for water holding of Tan mutton muscle. Bioinformatics analysis showed that most of these proteins were structural proteins and metabolic enzymes, which may lead to the change of meat quality by affecting the microstructure and metabolic pathway of muscle.

The Effect of a TLR4 Agonist/Cationic Liposome Adjuvant on Varicella-Zoster Virus Glycoprotein E Vaccine Efficacy: Antigen Presentation, Uptake, and Delivery to Lymph Nodes.

Adjuvant CIA09, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based cationic liposomes and the toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS), has been shown to enhance antibody and cellular immune responses to varicella-zoster virus (VZV) glycoprotein E (gE), recombinant tuberculosis vaccine antigen, and inactivated Japanese encephalitis vaccine. In this study, we investigated its modes of action using VZV gE as a model antigen. Liposomes adsorbed gE and cooperatively with dLOS promoted endocytosis-mediated cellular uptake of gE by mouse dendritic cells in vitro. CIA09 increased the stability and cellular uptake of the antigen at the muscle site of injection, and induced immune cell recruitment and cytokine and chemokine production, which led to efficient antigen delivery to draining lymph nodes. Mouse bone marrow-derived dendritic cells, pulsed with CIA09-adjuvanted gE, efficiently presented gE to antigen-specific T cells, inducing Th1-type biased immunity, as shown by high IFN-γ production. The data indicate that liposomes and dLOS cooperate in the adjuvant activity of CIA09 by promoting antigen uptake and delivery to lymph nodes as well as antigen presentation to T cells.

Cord Lining Mesenchymal Stem Cells Have a Modest Positive Effect on Angiogenesis in Hindlimb Ischemia

Purpose: We investigated the use of human Cord Lining Mesenchymal Stem Cells (CL-MSCs) (US Patent number 9,737,568), in a rabbit hindlimb ischemia model, and evaluated their potential in stimulating neovascularization. Allogenic human CL- MSCs could potentially be used to treat patients with lower limb ischemia and non-healing wounds.Methods: Twenty rabbits were divided into two separate groups. We created a hindlimb ischemia model surgically. At 21 and 49 days post-operatively, animals in the treatment group were injected with CL-MSCs (500,000 cells per 0.2 ml on each site) at 10 different sites (Quadriceps- 4 sites, Hamstrings- 4 sites and Calf-−2 sites) in the hindlimb muscles. The control group received only saline injection to the corresponding sites at the same time point as the treatment group. We then evaluated the effects of treatment on neovascularization by angiography, laser doppler perfusion imaging, as well as by histology. We evaluated the tissue samples for any signs of local immune reaction to the cell implantation. We also observed the rabbit clinically for any adverse effects after treatment.Results: We found a higher number of CD31 positive cells in the treatment group, with a greater number of capillaries found in the treated muscles. The Rectus Femoris demonstrated a median vessel count/muscle fiber of 0.121 for the treatment group, compared to 0.076 in the control group (median difference 0.04; 95% CI 0.001–0.11; p = 0.041). The Gastrocnemius demonstrated a median vessel count/muscle fiber of 0.175 for the treatment group, compared to 0.089 in the control group (median difference 0.087; 95% CI −0.006 to 0.234; p = 0.07). Blood perfusion quantification through Laser Doppler Perfusion Imaging (LDPI) also demonstrated a non-statistically significant increase in perfusion in favor of the treatment group. CL-MSCs demonstrated no toxicity associated morbidity and minimal local immune reaction to implantation.Conclusion: CL-MSCs have a positive effect on angiogenesis in a rabbit hindlimb ischemia model. This preliminary data is encouraging and paves the way for future large animal studies or for clinical trials.

Removal of Epididymal Visceral Adipose Tissue Prevents Obesity-Induced Multi-organ Insulin Resistance in Male Mice.

Obesity is associated with insulin resistance, an important risk factor of type 2 diabetes, atherogenic dyslipidemia, and nonalcoholic fatty liver disease. The major purpose of this study was to test hypothesize that prophylactic removal of epididymal visceral adipose tissue (VAT) prevents obesity-induced multi-organ (liver, skeletal muscle, adipose tissue) insulin resistance. Accordingly, we surgically removed epididymal VAT pads from adult C57BL/6J mice and evaluated in vivo and cellular metabolic pathways involved in glucose and lipid metabolism following chronic high-fat diet (HFD) feeding. We found that VAT removal decreases HFD-induced body weight gain while increasing subcutaneous adipose tissue (SAT) mass. Strikingly, VAT removal prevents obesity-induced insulin resistance and hyperinsulinemia and markedly enhances insulin-stimulated AKT-phosphorylation at serine-473 (Ser473) and threonine-308 (Thr308) sites in SAT, liver, and skeletal muscle. VAT removal leads to decreases in plasma lipid concentrations and hepatic triglyceride (TG) content. In addition, VAT removal increases circulating adiponectin, a key insulin-sensitizing adipokine, whereas it decreases circulating interleukin 6, a pro-inflammatory adipokine. Consistent with these findings, VAT removal increases adenosine monophosphate–activated protein kinase C phosphorylation, a major downstream target of adiponectin signaling. Data obtained from RNA sequencing suggest that VAT removal prevents obesity-induced oxidative stress and inflammation in liver and SAT, respectively. Taken together, these findings highlight the metabolic benefits and possible action mechanisms of prophylactic VAT removal on obesity-induced insulin resistance and hepatosteatosis. Our results also provide important insight into understanding the extraordinary capability of adipose tissue to influence whole-body glucose and lipid metabolism as an active endocrine organ.

Association of fibrosis in the bulge portion with hair follicle miniaturization in androgenetic alopecia

To the Editor: Androgenetic alopecia (AGA) is the most common hair loss disorder characterized by progressive hair miniaturization (in which large terminal hairs are gradual replaced by thin vellus hairs). Currently, the pathologic mechanism of AGA remains unclear. Growing evidence suggests that the bulge portion of hair follicles (HFs) plays an important role in the pathogenesis of AGA. The bulge area is located between the opening of the sebaceous gland and the attachment site of the arrector pili muscle (Supplemental Fig 1; available via Mendeley at https://doi.org/10.17632/w2xry2zp8y.1) and is a niche of multipotent stem cells that are necessary for regeneration of HFs, sebaceous glands, and epidermis.1Myung P. Ito M. Dissecting the bulge in hair regeneration.J Clin Invest. 2012; 122: 448-454Crossref PubMed Scopus (57) Google Scholar It has been proven that the failure of conversion from bulge stem cells to progenitor cells participates in AGA development.2Garza L.A. Yang C.-C. Zhao T. et al.Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.J Clin Invest. 2011; 121: 613-622Crossref PubMed Scopus (200) Google Scholar In our previous study, we discovered that fibrosis-related genes were overexpressed in the bugle portion of AGA-affected HFs,3Miao Y. Qu Q. Jiang W. et al.Identification of functional patterns of androgenetic alopecia using transcriptome profiling in distinct locations of hair follicles.J Invest Dermatol. 2018; 138: 972-975Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar implying that fibrosis participates in the disturbance of bulge stem cell conversion and leads to HF miniaturization. Hair diameter is an indicator of the miniaturization stage of HFs during AGA development. The average diameter of scalp terminal hair is approximately 80 μm, and 60 μm is a sensitive index to evaluate the progression of AGA.4Ishino A. Takahashi T. Suzuki J. Nakazawa Y. Iwabuchi T. Tajima M. Contribution of hair density and hair diameter to the appearance and progression of androgenetic alopecia in Japanese men.Br J Dermatol. 2014; 171: 1052-1059Crossref PubMed Scopus (17) Google Scholar In this study, we collected 300 follicular units from 10 Chinese men (8 patients with AGA and 2 healthy individuals, 23-41 years old; 30 follicular units/patient). The frontal HFs from patients with AGA were divided into 3 groups according to their diameters: early miniaturized HFs (EMHFs) of 80 to 100 μm, mediate miniaturized HFs (MMHFs) of 60 to 80 μm, and advanced miniaturized HFs (AMHFs) of 0 to 60 μm. The healthy occipital HFs (HOHFs) of patients with AGA and healthy frontal HFs (HFHFs) of healthy individuals were taken as control groups. All experiments were endorsed by the Ethics Committee of Southern Medical University and complied with the Declaration of Helsinki. All patients gave written informed consent before participation in this study. Hematoxylin-eosin staining showed that most of HFs in the MMHF group (85.6%) and AMHF group (93.5%) had some spindled cells with myofibroblast-like appearance in the bugle region, whereas few spindled cells were found in the EMHF (12.4%), HFHF (4.5%), and HOHF groups (5.6%) (Fig 1). Transmission electron microscopy was performed to confirm the presence of fibroblastoid cells within MMHF and AMHF bulge epithelium. As expected, collagen filaments were found within the cytoplasm of bulge keratinocytes (Supplemental Fig 2; available via Mendeley at https://doi.org/10.17632/w2xry2zp8y.1), indicating that fibrosis occurs within the bugle region of the MMHF and AMHF groups. The messenger RNA expression of fibrosis markers within the bulge region was analyzed in the 5 groups. Compared with HFHF and HOHF groups, expression of fibrosis markers (vimentin, fibronectin, Hsp47, and S100A4) were gradually upregulated in the EMHF, MMHF, and AMHF groups (Fig 2), suggesting that fibrosis of the bulge potion is positively correlated with the miniaturization of AGA-affected HFs. Our study shows that fibrosis occurs in the bulge region of AGA-affected HFs and is correlated with their miniaturization stage. The mechanism probably is that fibrosis of the bulge portion causes dysfunction of stem cells and inhibition of hair growth, finally leading to HF miniaturization. In conclusion, to our knowledge, our study puts forward a novel insight of AGA pathogenesis with a pathologic framework of “fibrosis–hair miniaturization,” suggesting that drugs inhibiting fibrosis are potential therapy to reverse hair miniaturization during AGA development. None disclosed.

Application of Spare Parts in Combination with Targeted Muscle Reinnervation Surgery.

Targeted muscle reinnervation is a contemporary technique designed to enhance an amputee's ability to operate a myoelectric prosthesis. This technique has been shown to decrease neuropathic pain, including neuroma and phantom limb pain. In certain amputations, especially forequarter and hindlimb levels, there may be no nearby recipient muscle sites, or the residual nerve may be too short to perform targeted muscle reinnervation. Applying the spare parts concept can help solve this problem by providing nerve autograft or additional muscle recipient sites within the spare parts flap for successful targeted muscle reinnervation surgery procedures. A retrospective review of all patients that underwent spare parts targeted muscle reinnervation reconstructions between 2016 and 2019 at two institutions was performed. Patients were assessed for healing, neuroma and phantom limb pain, and function. Twelve patients underwent targeted muscle reinnervation during spare parts reconstruction; eight were male and four were female. The mean patient age was 55.3 years (range, 16 to 72 years). For those with known soft-tissue deficit size, the surface area of the donor site spared by using spare parts reconstruction ranged from 216 to 856 cm2. None of the 12 patients subsequently experienced neuroma, and 75 percent had no phantom limb pain after 3 months. Three patients have obtained insurance-approved myoelectric prosthetics, and all three demonstrated intuitive control of targeted muscles. Using a spare parts reconstruction in conjunction with targeted muscle reinnervation may optimize reconstructive efforts in the setting of major limb amputations and aid in decreasing phantom limb and neuroma pain, and facilitate the possibility of functional prosthetic and/or myoelectric prosthesis use. Therapeutic, IV.

Injectable ROS-Scavenging Hydrogel With MSCs Promoted the Regeneration of Damaged Skeletal Muscle

Skeletal muscle injury is accompanied by inflammation, which is common in clinical practice. To data, there is no effective method to promote skeletal muscle regeneration. Here, we develop an ROS-scavenging hydrogels loaded with MSCs (Gel@MSCs), which offer a new strategy for modulating the local inflammatory microenvironment and improve the ability of skeletal muscle repair. The therapeutic scaffold consisting of ROS-degradable hydrogel could be injected into the injured site of skeletal muscle while MSCs contribute to new myofiber formation. We found that ROS-degradable hydrogel improved the survive and of MSCs ability of MSCs. Gel@MSCs inhibited the production of inflammatory factors by promoting polarization of M2 macrophages. In addition, it promoted the expression of genes and proteins related to myogenesis in MSCs. The ROS scavenged by hydrogels further reduced the inflammatory responses. We demonstrated that regeneration of damaged muscle tissue is achieved by local treatment of Gel@MSCs, due to the activated myogenic ability, increased M2 macrophages and reduced inflammatative environment.

Electromyography-Based Decoding of Dexterous, In-Hand Manipulation of Objects: Comparing Task Execution in Real World and Virtual Reality

The increased use of Virtual and Augmented Reality based systems necessitates the development of more intuitive and unobtrusive means of interfacing. Over the last years, Electromyography (EMG) based interfaces have been employed for interaction with robotic and computer applications, but no studies have been carried out to investigate the continuous decoding of the effects of human motion (e.g., manipulated object behavior) in simulated and virtual environments. In this work, we compare the object motion decoding accuracy of an EMG based learning framework for two different dexterous manipulation scenarios: i) for simulated objects handled by a teleoperated model of a hand within a virtual environment and ii) for real, everyday life objects manipulated by the human hand. To do that, we utilize EMG activations from 16 muscle sites (9 on the hand and 7 on the forearm). The object motion decoding is formulated as a regression problem using the Random Forests methodology. A 5-fold cross validation procedure is used for model assessment purposes and the feature variable importance values are calculated for each model. The decoding accuracy for the real world is considerably higher than the virtual world. Each of the objects examined had a single manipulation motion that offered the highest estimation accuracy across both worlds. This study also shows that it is feasible to decode the object motions using just the myoelectric activations of the muscles of the forearm and the hand. This is particularly surprising since simulations lacked haptic feedback and the ability to account for other dynamic phenomena like friction and contact rolling.