Conductive Polymeric-Based Electroactive Scaffolds for Tissue Engineering Applications: Current Progress and Challenges from Biomaterials and Manufacturing Perspectives.

The practice of combining external stimulation therapy alongside stimuli-responsive bio-scaffolds has shown massive potential for tissue engineering applications. One promising example is the combination of electrical stimulation (ES) and electroactive scaffolds because ES could enhance cell adhesion and proliferation as well as modulating cellular specialization. Even though electroactive scaffolds have the potential to revolutionize the field of tissue engineering due to their ability to distribute ES directly to the target tissues, the development of effective electroactive scaffolds with specific properties remains a major issue in their practical uses. Conductive polymers (CPs) offer ease of modification that allows for tailoring the scaffold's various properties, making them an attractive option for conductive component in electroactive scaffolds. This review provides an up-to-date narrative of the progress of CPs-based electroactive scaffolds and the challenge of their use in various tissue engineering applications from biomaterials perspectives. The general issues with CP-based scaffolds relevant to its application as electroactive scaffolds were discussed, followed by a more specific discussion in their applications for specific tissues, including bone, nerve, skin, skeletal muscle and cardiac muscle scaffolds. Furthermore, this review also highlighted the importance of the manufacturing process relative to the scaffold's performance, with particular emphasis on additive manufacturing, and various strategies to overcome the CPs' limitations in the development of electroactive scaffolds.

Treatment Update of Port-Wine Stain: A Narrative Review.

BACKGROUND: Port-wine stain (PWS) is a congenital vascular malformation affecting 0.3–0.5% of normal population. These characteristic lesions arise due to the interplay of vascular, neural, and genetic factors. Treatment options include lasers, cosmetic tattooing, electrotherapy, cryosurgery, derma-abrasion, and skin grafting; however, none of these treatment alternatives appears to be satisfactory and is unable to provide consistent, satisfactory responses or even complete cures. Currently, laser is the treatment of choice, as it is comparatively safe and more effective than other procedures. The most commonly used modality is pulsed dye laser (PDL). The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) to January 2020 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5005.

Cluster headache pathophysiology - insights from current and emerging treatments.

Cluster headache is a debilitating primary headache disorder that affects approximately 0.1% of the population worldwide. Cluster headache attacks involve severe unilateral pain in the trigeminal distribution together with ipsilateral cranial autonomic features and a sense of agitation. Acute treatments are available and are effective in just over half of the patients. Until recently, preventive medications were borrowed from non-headache indications, so management of cluster headache is challenging. However, as our understanding of cluster headache pathophysiology has evolved on the basis of key bench and neuroimaging studies, crucial neuropeptides and brain structures have been identified as emerging treatment targets. In this Review, we provide an overview of what is known about the pathophysiology of cluster headache and discuss the existing treatment options and their mechanisms of action. Existing acute treatments include triptans and high-flow oxygen, interim treatment options include corticosteroids in oral form or for greater occipital nerve block, and preventive treatments include verapamil, lithium, melatonin and topiramate. We also consider emerging treatment options, including calcitonin gene-related peptide antibodies, non-invasive vagus nerve stimulation, sphenopalatine ganglion stimulation and somatostatin receptor agonists, discuss how evidence from trials of these emerging treatments provides insights into the pathophysiology of cluster headache and highlight areas for future research.

Protection of retinal ganglion cells in glaucoma: Current status and future.

Glaucoma is a neuropathic disease that causes optic nerve damage, loss of retinal ganglion cells (RGCs), and visual field defects. Most glaucoma patients have no early signs or symptoms. Conventional pharmacological glaucoma medications and surgeries that focus on lowering intraocular pressure are not sufficient; RGCs continue to die, and the patient's vision continues to decline. Recent evidence has demonstrated that neuroprotective approaches could be a promising strategy for protecting against glaucoma. In the case of glaucoma, neuroprotection aims to prevent or slow down disease progression by mitigating RGCs death and optic nerve degeneration. Notably, new pharmacologic medications such as antiglaucomatous agents, antibiotics, dietary supplementation, novel neuroprotective molecules, neurotrophic factors, translational methods such as gene therapy and cell therapy, and electrical stimulation-based physiotherapy are emerging to attenuate the death of RGCs, or to make RGCs resilient to attacks. Understanding the roles of these interventions in RGC protection may offer benefits over traditional pharmacological medications and surgeries. In this review, we summarize the recent neuroprotective strategy for glaucoma, both in clinical trials and in laboratory research.

Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions.

This paper is an interdisciplinary narrative review of efficacious non-invasive therapies that are increasingly used to restore function in people with chronic spinal cord injuries (SCI). First presented are the secondary injury cascade set in motion by the primary lesion and highlights in therapeutic development for mitigating the acute pathophysiologic process. Then summarized are current pharmacological strategies for modulation of noradrenergic, serotonergic, and dopaminergic neurotransmission to enhance recovery in bench and clinical studies of subacute and chronic SCI. Last examined is how neuromechanical devices (i.e., electrical stimulation, robotic assistance, brain-computer interface, and augmented sensory feedback) could be comprehensively engineered to engage efferent and afferent motosensory pathways to induce neuroplasticity-based neural pattern generation. Emerging evidence shows that computational models of the human neuromusculoskeletal system (i.e., human digital twins) can serve as functionalized anchors to integrate different neuromechanical and pharmacological interventions into a single multimodal prothesis. The system, if appropriately built, may cybernetically optimize treatment outcomes via coordination of heterogeneous biosensory, system output, and control signals. Overall, these rehabilitation protocols involved neuromodulation to evoke beneficial adaptive changes within spared supraspinal, intracord, and peripheral neuromuscular circuits to elicit neurological improvement. Therefore, qualitatively advancing the theoretical understanding of spinal cord neurobiology and neuromechanics is pivotal to designing new ways to reinstate locomotion after SCI. Future research efforts should concentrate on personalizing combination therapies consisting of pharmacological adjuncts, targeted neurobiological and neuromuscular repairs, and brain-computer interfaces, which follow multimodal neuromechanical principles.

Cost Effectiveness of Sacral Neuromodulation and OnabotulinumtoxinA in Managing Refractory Idiopathic Overactive Bladder.

Little information from clinical and modelled studies are available on cost effectiveness of OnabotulinumtoxinA and SNM for the treatment of idiopathic overactive bladder. We aimed to summarize the evidence in this regard from different healthcare systems. Seven studies from 5 countries were reviewed. Some modelled studies with a 10-year time frame showed that sacral neuromodulation became dominant long-term; others suggested OnabotulinumtoxinA was more cost effective at <5 years. There was considerable heterogeneity in the base case/sensitivity analysis and statistical modelling among the studies. Clinical studies with longer term follow-up will help determine cost effectiveness more accurately.

The effect of additional neuromuscular electrical stimulation applied to erector spinae muscles on functional capacity, balance and mobility in post-stroke patients.

OBJECTIVE: The aim of this study was to investigate the effects of neuromuscular electric stimulation applied to the erector spinae on balance, motor function and functional capacity in patients with stroke in a randomized controlled trial. METHODS: Sixty patients with stroke were recruited and randomly distributed into two groups: control group and neuromuscular electric stimulation group. All participants underwent conventional physical therapy five times a week for six weeks. The neuromuscular electric stimulation group received additional electrical stimulation. Outcome measures were evaluated with Brunnel Balance Assessment, Stroke Rehabilitation Movement Assessment, Functional Ambulation Classification, Adapted Patient Evaluation and Conference System, Postural Assesment Scale for Stroke patients, Short Form-36, and Minimental State Examination scales. RESULTS: Significant differences were observed in all scores at the end of the study in both groups. Postural Assesment Scale for Stroke patients and Stroke Rehabilitation Movement Assessment scores were higher in the neuromuscular electric stimulation group compared to the control group (p < 0.05). All the other scores were not statistically significant. CONCLUSION: It is recommended to evaluate and treat trunk muscle, which is usually neglected in treatment, and to consider the combination of conventional treatment and neuromuscular electric stimulation when designing an ideal rehabilitation program.

Sacral nerve stimulation ameliorates colonic barrier functions in a rodent model of colitis.

BACKGROUND: The mucosal barrier damage is recognized as one of the key factors in the pathogenesis of colitis. While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown. METHODS: In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham-SNS for 10 days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight-junction proteins involved in regulating permeability and the FITC-dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system. KEY RESULTS: SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro-inflammatory cytokines (TNF-α, IL-6). SNS increased the expression of Zonula Occludens-1, Occludin, Claudin-1, and Junctional adhesion molecule-A in the colon tissue. The FITC-dextran test showed that the colonic permeability was lower with SCS than sham-SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub-P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity. CONCLUSIONS & INFERENCES: SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.

Effects of whole-body electromyostimulation exercise and caloric restriction on cardiometabolic risk profile and muscle strength in obese women with the metabolic syndrome: a pilot study.

Obesity, particularly in conjunction with further cardiometabolic risk factors, is associated with an increased risk of cardiovascular disease and mortality. Increased physical activity and dietary modifications are cornerstones of therapeutic interventions to treat obesity and related risk factors. Whole-body electromyostimulation (WB-EMS) has emerged as an innovative, time-efficient type of exercise that can provide positive effects on body composition and muscle strength. However, the impact of WB-EMS on cardiometabolic health in obese individuals with metabolic syndrome (MetS) has yet to be determined. The aim of this pilot study was, therefore, to investigate the feasibility and effects of WB-EMS on cardiometabolic risk markers and muscle strength in obese women diagnosed with MetS. Twenty-nine obese women (56.0 ± 10.9 years, BMI: 36.7 ± 4.6 kg/m2) with the clinical diagnosis of MetS were randomized to either 12 weeks of WB-EMS (n = 15) or an inactive control group (CON, n = 14). Both groups received nutritional counseling (aim: -500 kcal energy deficit/day). WB-EMS was performed 2x/week (20 min/session). Body composition, maximum strength (Fmax) of major muscle groups, selected cardiometabolic risk indices and the metabolic syndrome Z-score (MetS-Z) were determined baseline and after the intervention. WB-EMS was well tolerated and no adverse events occurred. Body weight was significantly reduced in both groups by an average of ~3 kg (P < 0.01). The body fat percentage was only decreased in the WB-EMS group (P = 0.018). Total cholesterol concentrations decreased in the WB-EMS group (P = 0.018) and in CON (P = 0.027). Only the WB-EMS group increased Fmax significantly in all major muscle groups (P < 0.05) and improved the overall cardiometabolic risk score (MetS-Z, P = 0.029). This pilot study indicates that WB-EMS can be considered as a feasible and time-efficient exercise option for improving body composition, muscle strength and cardiometabolic health in obese women with MetS. Moreover, these findings underpin the crucial role of exercise during weight loss interventions in improving health outcomes.

A Quasi-Experimental Evaluation of an Education Program for the Use of Electrical Stimulation Therapy to Heal Pressure Injuries.

Electrical stimulation (E-Stim) involves applying low levels of electrical current. Despite high-level recommendations for E-stim use in many pressure injury (PrI) best practice treatment guidelines, clinicians seldom use E-Stim. PURPOSE: This quasi-experimental design study aimed to determine whether an educational program could improve health care providers' knowledge and attitudes regarding the use of E-Stim for treating PrIs in community-dwelling individuals with spinal cord injury living in 1 region of Ontario, Canada. METHODS: An educational intervention based on a university-level continuing education program was developed as part of a multifaceted knowledge mobilization project. Health care providers (eg, nurses, physicians, and allied health professionals) from multiple agencies were invited to participate. The instructional series included 8 online modules on background theory and knowledge and a hands-on workshop that familiarized participants with the equipment necessary to deliver E-Stim. Knowledge (percentage of correct answers using a knowledge test developed by the research team) and attitudes (assessed using the E-Stim Attitude Survey in which items were scored using a 5-point Likert scale (where 0 indicated a negative attitude and 5 a positive attitude) were evaluated 3 times (pre-education, post-online, and post-workshop). Data were aggregated into unit-weighted averaged composites of 3 attitude subscales (resources, evidence-based practice, and education), which were compared before and after educational sessions using a linear mixed effect model. RESULTS: Among the 83 participants, a significant increase in knowledge scores was noted from pre-education (55.9%) to post-online (78.4%) and post-workshop (78.0%) (X² [2] = 89.34; P <.001). A significant increase in attitude scores was noted across time points (resources: X² [2] = 27.32, P <.0001; evidence-based practice: X² [2] = 38.93, P <.0001; and education: X² [2] = 92.88, P <.0001). For the evidence-based practice subscale, attitude increased significantly post-online (t[127] = 6.03, P <.0001). For the resources subscale, a significant increase was detected after post-workshop (t[113] = 5.23, P <.001]. CONCLUSIONS: Online education increased health care providers' knowledge about E-Stim; however, hands-on workshops were required to change certain attitudes about the use of E-Stim for wound healing. Further research is required to evaluate 1) whether a change in knowledge and attitude scores translates to a practice change for health care providers and 2) the potential importance of ongoing coaching and mentorship for a sustainable change in the clinical setting.

A therapeutic effect for males with spinal cord injury using abdominal functional electrical stimulation for sexual functioning.

INTRODUCTION: Sexual functioning is a high priority for people with a spinal cord injury (SCI) yet this area has received little attention. Two SCI case reports are presented which suggests there may be greater potential for the recovery of sexual functioning than previously recognised. CASE PRESENTATION: A 74-year-old SCI male (AIS D, C5/C6) and a 36-year-old SCI male (AIS A, T4/T5) were treated for neurogenic bowel using 6 weeks of abdominal FES (ABFES) (40 Hz, 300 µ pulse width (current typically 30-60 MA) simultaneously delivered (8 s contraction with 2 s ramps and 3 s off period) from both channels). The 74-year-old AIS D, C5/C6 participant reported improved strength and duration of erectile function after using ABFES for 3 weeks. The 36-year-old AIS A, T4/T5 participant reported improvements in ejaculatory function and urine flow. Both reported a reduction in time required for bowel management. DISCUSSION: The findings could be attributed to an improved vascularisation of the abdominal area, an improved body image and self-esteem, direct innervation of nerves involved in parasympathetic pathways or innervation of the T11/T1 area implicated in the alternative psychogenic pathway. Both participants reported they had not used ABFES during sexual activity suggesting a therapeutic effect from the treatment.

[Urology goes electric-electrotherapy : Modern therapies in the treatment of modern diseases-examples from urology]. / Die Urologie wird elektrisch ­ Elektrotherapie : Moderne Therapien zur Behandlung moderner Erkrankungen ­ Beispiele aus der Urologie.

The significance of electricity for medicine in the modern industrial age should not be underestimated. Particularly in connection with neurasthenia, electrotherapeutic approaches also experienced a boom for domestic use. Thus, electrotherapy reached urology just as it was becoming established as a medical specialty. We analyzed urological manuals and textbooks and objects in the W. P. Didusch Center for Urologic History and the Museum zur Geschichte der Urologie in Berlin to present the wide range of indications for electrotherapy in the emerging field of urology from impotence to urethral strictures and try to highlight the variability of their importance over time.

New neuromodulation techniques for treatment resistant depression.

In the treatment of depression, when pharmacotherapy, psychotherapy and the oldest brain stimulation techniques are deadlocked, the emergence of new therapies is a necessary development. The field of neuromodulation is very broad and controversial. This article provides an overview of current progress in the technological advances in neuromodulation and neurostimulation treatments for treatment-resistant depression: magnetic seizure therapy; focal electrically administered seizure therapy; low field magnetic stimulation; transcranial pulsed electromagnetic fields; transcranial direct current stimulation; epidural cortical stimulation; trigeminal nerve stimulation; transcutaneous vagus nerve stimulation; transcranial focussed ultrasound; near infra-red transcranial radiation; closed loop stimulation. The role of new interventions is expanding, probably with more efficacy. Nowadays, still under experimentation, neuromodulation will probably revolutionise the field of neuroscience. At present, major efforts are still necessary before that these therapies are likely to become widespread.Key pointsThere is a critical need for new therapies for treatment resistant depression.Newer therapies are expanding. In the future, these therapies, as an evidence-based adjunctive treatments, could offer a good therapeutic choice for the patients with a TRD.The current trend in the new neuromodulation therapies is to apply a personalised treatment.These news therapies can be complementary.That treatment approaches can provide clinically significant benefits.

Perspectives on the current developments with neuromodulation for the treatment of epilepsy.

Introduction: As deep brain stimulation revolutionized the treatment of movement disorders in the late 80s, neuromodulation in the treatment of epilepsy will undoubtedly undergo transformative changes in the years to come with the exponential growth of technological development moving into mainstream practice; the appearance of companies such as Facebook, Google, Neuralink within the realm of brain-computer interfaces points to this trend.Areas covered: This perspective piece will talk about the history of brain stimulation in epilepsy, current-approved treatments, technical developments and the future of neurostimulation.Expert opinion: Further understanding of the brain alongside machine learning and innovative technology will be the future of neuromodulation for the treatment of epilepsy. All of these innovations and advances should pave the way toward overcoming the vexing underutilization of surgery in the therapeutic armamentarium against medically refractory seizures, given the implicit advantage of a neuromodulatory rather than neurodestructive approach.

History of Cranial Nerve-Implanted Stimulators in Otolaryngology.

This article aims to clearly understand the historical development of cranial nerve-implanted stimulators in otolaryngology. The authors also discuss cranial nerve history; initial theory of the functional concept of animal spirit; electrical nerve impulse theory; first electrical otolaryngology cranial nerve stimulation devices; and the development of implanted stimulators.