Metabolic Biomarkers for the Early Detection of Cancer Cachexia

Background: Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible. It is therefore critical to detect cachexia as early as possible. In this study we applied a metabolomics approach to search for early biomarkers of cachexia.Methods: Multi-platform metabolomics analyses were applied to the murine Colon-26 (C26) model of cachexia. Tumor bearing mice (n = 5) were sacrificed every other day over the 14-day time course and control mice (n = 5) were sacrificed every fourth day starting at day 2. Linear regression modeling of the data yielded metabolic trajectories that were compared with the trajectories of body weight and skeletal muscle loss to look for early biomarkers of cachexia.Results: Weight loss in the tumor-bearing mice became significant at day 9 as did the loss of tibialis muscle. The loss of muscle in the gastrocnemius and quadriceps was significant at day 7. Reductions in amino acids were among the earliest metabolic biomarkers of cachexia. The earliest change was in methionine at day 4. Significant alterations in acylcarnitines and lipoproteins were also detected several days prior to weight loss.Conclusion: The results of this study demonstrate that metabolic alterations appear well in advance of observable weight loss. The earliest and most significant alterations were found in amino acids and lipoproteins. Validation of these results in other models of cachexia and in clinical studies will pave the way for a clinical diagnostic panel for the early detection of cachexia. Such a panel would provide a tremendous advance in cachectic patient management and in the design of clinical trials for new therapeutic interventions.

Neurophysiological Effects of Dry Needling in Patients with Neck Pain, A Randomized Clinical Trial

The purpose was to determine the efficacy of deep dry needling (DDN) applied on an active myofascial trigger point (MTrP) versus a latent-MTrP versus a non-MTrP location, on pain reduction and cervical disability, in patients with chronic neck pain. A randomized, double-blind clinical trial design was used. A sample of 65 patients was divided into non-MTrP-DDN, active-MTrP-DDN and latent-MTrP-DDN groups. The visual analog scale (VAS), reproduction of the patient’s pain, number of local twitch responses, pressure pain threshold (PPT) and Neck Disability Index (NDI) were assessed before, during and after the intervention and up to 1 month post-intervention. The active-MTrP-DDN-group reduced pain intensity more than non-MTrP-DDN-group after a week and a month (p<0.01). Active-MTrP-DDN-group showed the greatest improvement in tibialis muscle PPT. An association was found with a higher percentage of subjects in whom their neck pain was reproduced when the active-MTrP (77.3%) and the latent-MTrP (81.8%) were treated. The application of DDN on an active-MTrP in the upper trapezius muscle shows greater improvements in pain intensity after one week and one month post-intervention, as well as lesser improvement in PPT in the tibialis muscle, compared to DDN applied in latent-MTrPs or outside of MTrPs in patients with neck pain

Smart Protocols for Physical Therapy of Foot Drop Based on Functional Electrical Stimulation: A Case Study

Functional electrical stimulation (FES) is used for treating foot drop by delivering electrical pulses to the anterior tibialis muscle during the swing phase of gait. This treatment requires that a patient can walk, which is mostly possible in the later phases of rehabilitation. In the early phase of recovery, the therapy conventionally consists of stretching exercises, and less commonly of FES delivered cyclically. Nevertheless, both approaches minimize patient engagement, which is inconsistent with recent findings that the full rehabilitation potential could be achieved by an active psycho-physical engagement of the patient during physical therapy. Following this notion, we proposed smart protocols whereby the patient sits and ankle movements are FES-induced by self-control. In six smart protocols, movements of the paretic ankle were governed by the non-paretic ankle with different control strategies, while in the seventh voluntary movements of the paretic ankle were used for stimulation triggering. One stroke survivor in the acute phase of recovery participated in the study. During the therapy, the patient’s voluntary ankle range of motion increased and reached the value of normal gait after 15 sessions. Statistical analysis did not reveal the differences between the protocols in FES-induced movements.

Current Concepts Review: Common Peroneal Nerve Palsy After Knee Dislocations

Dislocation of the native knee represents a challenging injury, further complicated by the high rate of concurrent injury to the common peroneal nerve (CPN). Initial management of this injury requires a thorough neurovascular examination, given the prevalence of popliteal artery injury and limb-threatening ischemia. Further management of a knee dislocation with associated CPN palsy requires coordinated care involving the sports surgeon for ligamentous knee reconstruction and the peripheral nerve surgeon for staged or concurrent peroneal nerve decompression and/or reconstruction. Finally, the foot and ankle surgeon is often required to manage a foot drop with a distal tendon transfer to restore foot dorsiflexion. For instance, the Bridle Procedure—a modification of the anterior transfer of the posterior tibialis muscle, under the extensor retinaculum, with tri-tendon anastomosis to the anterior tibial and peroneus longus tendons at the anterior ankle—can successfully return patients to brace-free ambulation and athletic function following CPN palsy. Cross-discipline coordination and collaboration is essential to ensure appropriate timing of operative interventions and ensure maintenance of passive dorsiflexion prior to tendon transfer.

Immediate Effects of Kinesio Taping of Tibialis Anterior and Ankle Joint on Mobility and Balance Ability for Chronic Hemiparesis: Randomized Controlled Cross-Sectional Design

Background Stroke patients with hemiparesis are generally described as being slow and suffering a balance disability. Objective The purpose of this cross-sectional single-blind study was to evaluate the immediate effects of Kinesio taping of tibialis anterior and quadriceps on the mobility and balance ability in individuals with chronic hemiparetic stroke. Methods Thirty-three subjects participated in this study. Participants were divided into 3 groups: Ankle Kinesio taping (AKT) group, a placebo (PKT) group, and a control (NKT) group. The AKT group underwent Kinesio tapping of ankle joint and tibialis muscle, PKT group underwent placebo taping, and NKT group underwent no Kinesio taping. All participants were assessed before and after taping training using timed up and go test (TUG), timed up and down stairs test (TUDS), and balance ability. Results After taping training, the AKT group showed significant improvement in mobility and balance ability compared to the PKT group and NKT group (p < 0.05). The results of this study confirmed that Kinesio taping was effective to the balance and mobility abilities of patients with chronic hemiparetic stroke. Conclusions This study suggested Kinesio taping as an effective intervention to increase the mobility and balance abilities of patients with chronic hemiparetic stroke. Therefore, this study are believed to provide the baseline information to effectively improve the balance and mobility abilities of patients with chronic hemiparetic stroke during the rehabilitation treatment in the future.

Human iPS Cells Derived Skeletal Muscle Progenitor Cells Promote Myoangiogenesis and Restore Dystrophin in Duchenne Muscular Dystrophic Mice

Background and ObjectiveDuchenne muscular dystrophy (DMD) is caused by mutations of the gene that encodes the protein dystrophin. Loss of dystrophin leads to severe and progressive muscle-wasting in both skeletal and heart muscles. Human induced pluripotent stem cells (hiPSCs) and their derivatives offer important opportunities to treat a number of diseases. Here, we investigated whether givinostat, a histone deacetylase inhibitor (HDACi), could reprogram hiPSCs into muscle progenitor cells (MPC) for DMD treatment.Methods and ResultsMPC generated by CHIR99021 and givinostat (Givi) small molecules from multiple hiPSCs expressed myogenic makers (Pax7, desmin) and were differentiated into myotubes expressing MF20 upon culture in specific differentiation medium. These MPC exhibited superior proliferation and migration capacity determined by CCK-8, colony and migration assays compared to control-MPC generated by CHIR99021 and fibroblast growth factor (FGF). Upon transplantation in hind limb of Mdx/SCID mice with cardiotoxin (CTX) induced injury, these MPC showed higher engraftment and restoration of dystrophin than treatment with control-MPC and human myoblasts. In addition, treated muscle with these MPC showed significantly limited infiltration of inflammatory cells and reduced muscle necrosis and fibrosis. A number of these cells were engrafted under basal lamina expressing Pax7, which were capable of generating new muscle fibers after additional injury. Extracellular vesicles released from these cells promoted angiogenesis after reinjury.ConclusionWe successfully generated integration free MPC from multiple hiPS cell lines using CHIR99021 and Givi. Givinostat induced MPC showed marked and impressive regenerative capabilities and restored dystrophin in injured tibialis muscle compared to control MPC. Additionally, MPC generated by Givi also seeded the stem cell pool in the treated muscle. It is concluded that hiPSCs pharmacologically reprogrammed into MPC with a small molecule, Givi with anti-oxidative, anti-inflammatory and muscle gene promoting properties might be an effective cellular source for treatment of muscle injury and restoration of dystrophin in DMD.

Influence of electroacupuncture stimulation on skin temperature, skin blood flow, muscle blood volume and pupil diameter

Objective: To examine the effect of electroacupuncture (EA) stimulation on multiple physiological indices and to evaluate both local and systemic physiological responses induced by the stimulation. Methods: 15 healthy male college students participated in an experimental crossover study. They received two kinds of interventions: one with EA stimulation and one without EA stimulation on different days. Two disposable acupuncture needles were inserted at two traditional acupuncture points (ST36 and ST38), located along the anterior tibialis muscle. EA stimulation was administered for 10 min. Skin temperature (ST), skin blood flow (SBF) and muscle blood volume (MBV) were recorded near the stimulation sites, while the pupil diameter (PD) was measured before, during and after the interventions. Results: ST, SBF and MBV increased significantly following EA stimulation. PD of the right and left eyes decreased significantly following EA stimulation. There was a significant difference in ST responses between the groups (P=0.001). For SBF, MBV and PD, no significant differences were demonstrated between the groups. Conclusions: Our study showed that 10 min of EA stimulation increased ST, SBF and MBV, and decreased PD, compared to baseline, while no significant change was observed in the control group. This suggests that EA stimulation alters local blood flow and ST, and these responses are likely mediated via segmental spinal reflexes, supraspinal reflexes involving parasympathetic activation, and other mechanisms.