Magnetic mediators for ultrasound theranostics.

The theranostics paradigm is based on the concept of combining therapeutic and diagnostic modalities into one platform to improve the effectiveness of treatment. Combinations of multiple modalities provide numerous medical advantages and are enabled by nano- and micron-sized mediators. Here we review recent advancements in the field of ultrasound theranostics and the use of magnetic materials as mediators. Several subdisciplines are described in detail, including controlled drug delivery and release, ultrasound hyperthermia, magneto-ultrasonic heating, sonodynamic therapy, magnetoacoustic imaging, ultrasonic wave generation by magnetic fields, and ultrasound tomography. The continuous progress and improvement in theranostic materials, methods, and physical computing models have created undeniable possibilities for the development of new approaches. We discuss the prospects of ultrasound theranostics and possible expansions of other studies to the theranostic context.

[Vision restoration: science fiction or reality?] / Restauration de la vision: Science-fiction ou réalité ?

Visual prostheses aim at restoring useful vision to patients who have become blind. This useful vision should enable them to regain autonomy in society for navigation, face recognition or reading. Two retinal prostheses have already obtained market authorization for patients affected by retinal dystrophies while a new device is in clinical trials for patients affected by age-related macular degeneration. Various prostheses, in particular cortical prostheses, are currently in clinical trials for optic neuropathies (glaucoma). Optogenetic therapy, an alternative strategy, has now reached the stage of clinical trials at the retinal level while moving forward at the cortical level. Other innovating strategies have obtained proofs of concepts in rodents but require a further validation in large animals prior to their evaluation on patients. Restoring vision should therefore become a reality for many patients even if this vision will not be as extensive and perfect as natural vision.

TITLE: Restauration de la vision: Science-fiction ou réalité ? ABSTRACT: Les prothèses visuelles ont pour objet de redonner une vision utile aux patients devenus aveugles. Cette vision utile doit leur permettre de retrouver une autonomie dans la société pour leurs déplacements, la reconnaissance des visages ou la lecture. Plusieurs prothèses rétiniennes ont déjà obtenu l'autorisation de mise sur le marché pour les dystrophies rétiniennes alors qu'un nouveau dispositif est en essai clinique pour la dégénérescence maculaire liée à l'âge. D'autres prothèses, notamment corticales, sont en essai clinique pour les neuropathies optiques (glaucome). Des stratégies alternatives, comme la thérapie optogénétique, ont également atteint le stade des essais cliniques. D'autres ont été évaluées sur les rongeurs, attendant leur validation sur le gros animal. Revoir devrait donc prochainement devenir une réalité pour de nombreux patients, même si cette vision ne sera ni aussi étendue, ni aussi parfaite que la vision naturelle.

Nano-Carriers of Combination Tumor Physical Stimuli-Responsive Therapies.

With the development of nanotechnology, Tumor Physical Stimuli-Responsive Therapies (TPSRTs) have reached a new stage because of the remarkable characteristics of nanocarriers. The nanocarriers enable such therapies to overcome the drawbacks of traditional therapies, such as radiotherapy or chemotherapy. To further explore the possibility of the nanocarrier-assisted TPSRTs, scientists have combined different TPSRTs via; the platform of nanocarriers into combination TPSRTs, which include Photothermal Therapy (PTT) with Magnetic Hyperthermia Therapy (MHT), PTT with Sonodynamic Therapy (SDT), MHT with Photodynamic Therapy (PDT), and PDT with PTT. To achieve such therapies, it requires to fully utilize the versatile functions of a specific nanocarrier, which depend on a pellucid understanding of the traits of those nanocarriers. This review covers the principles of different TPSRTs and their combinations, summarizes various types of combination TPSRTs nanocarriers and their therapeutic effects on tumors, and discusses the current disadvantages and future developments of these nanocarriers in the application of combination TPSRTs.

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.

Biomaterials and Magnetic Stem Cell Delivery in the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious trauma, which often results in a permanent loss of motor and sensory functions, pain and spasticity. Despite extensive research, there is currently no available therapy that would restore the lost functions after SCI in human patients. Advanced treatments use regenerative medicine or its combination with various interdisciplinary approaches such as tissue engineering or biophysical methods. This review summarizes and critically discusses the research from specific interdisciplinary fields in SCI treatment such as the development of biomaterials as scaffolds for tissue repair, and using a magnetic field for targeted cell delivery. We compare the treatment effects of synthetic non-degradable methacrylate-based hydrogels and biodegradable biological scaffolds based on extracellular matrix. The systems using magnetic fields for magnetically guided delivery of stem cells loaded with magnetic nanoparticles into the lesion site are then suggested and discussed.

Biophysical stimulation of bone and cartilage: state of the art and future perspectives.

INTRODUCTION: Biophysical stimulation is a non-invasive therapy used in orthopaedic practice to increase and enhance reparative and anabolic activities of tissue. METHODS: A sistematic web-based search for papers was conducted using the following titles: (1) pulsed electromagnetic field (PEMF), capacitively coupled electrical field (CCEF), low intensity pulsed ultrasound system (LIPUS) and biophysical stimulation; (2) bone cells, bone tissue, fracture, non-union, prosthesis and vertebral fracture; and (3) chondrocyte, synoviocytes, joint chondroprotection, arthroscopy and knee arthroplasty. RESULTS: Pre-clinical studies have shown that the site of interaction of biophysical stimuli is the cell membrane. Its effect on bone tissue is to increase proliferation, synthesis and release of growth factors. On articular cells, it creates a strong A2A and A3 adenosine-agonist effect inducing an anti-inflammatory and chondroprotective result. In treated animals, it has been shown that the mineralisation rate of newly formed bone is almost doubled, the progression of the osteoarthritic cartilage degeneration is inhibited and quality of cartilage is preserved. Biophysical stimulation has been used in the clinical setting to promote the healing of fractures and non-unions. It has been successfully used on joint pathologies for its beneficial effect on improving function in early OA and after knee surgery to limit the inflammation of periarticular tissues. DISCUSSION: The pooled result of the studies in this review revealed the efficacy of biophysical stimulation for bone healing and joint chondroprotection based on proven methodological quality. CONCLUSION: The orthopaedic community has played a central role in the development and understanding of the importance of the physical stimuli. Biophysical stimulation requires care and precision in use if it is to ensure the success expected of it by physicians and patients.

Echocardiographic Changes in Patients Implanted With a Fully Magnetically Levitated Left Ventricular Assist Device (Heartmate 3).

BACKGROUND: The Heartmate 3 (HM3) is a Conformiteé Européenne mark-approved left ventricular (LV) assist device (LVAD) with fully magnetically levitated rotor and features consisting of a wide range operational speeds, wide flow paths, and artificial pulse. We performed a hemodynamic-echocardiographic speed optimization evaluation in HM3-implanted patients to achieve optimal LV- and right ventricular (RV) shape. METHODS AND RESULTS: Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization. Three-dimensional echocardiographic (3DE) LV and RV datasets (Philips) were acquired, and volumetric (Tomtec) and shape (custom software) analyses were performed (LV: sphericity, conicity; RV: septal and free-wall curvatures). Data were recorded at up to 13 speed settings. Speed changes were in 100-rpm steps, starting at 4600 rpm and ramping up to 6200 rpm. 3DE was feasible in 50% of the patients. Mean original speed was 5306 ± 148 rpm. LV end-diastolic (ED) diameter (-0.15 ± 0.09 cm/100 rpm) and volumes (ED: 269 ± 109 mL to 175 ± 90 mL; end-systolic [ES]: 234 ± 111 mL to 146 ± 81 mL) progressively decreased as the shape became less spherical and more conical; RV volumes initially remained stable, but at higher speeds increased (ED: from 148 ± 64 mL to 181 ± 92 mL; ES: 113 ± 63 mL to 130 ± 69 mL). On average, the RV septum became less convex (bulging toward the LV) at the highest speeds. CONCLUSIONS: LV and RV shape changes were noted in HM3-supported patients. Although a LV volumetric decrease and shape improvement was consistently noted, RV volumes grew in response to increase in speed above a certain point. A next concern would be whether understanding of morphologic and function changes in LV and RV during LVAD speed change assessed with the use of 3DE helps to optimize LVAD speed settings and improve clinical outcomes.

Does Decreased Surgical Stress Really Improve the Psychosocial Health of Early-onset Scoliosis Patients?: A Comparison of Traditional Growing Rods and Magnetically-controlled Growing Rods Patients Reveals Disappointing Results.

STUDY DESIGN: Cross-sectional case-control study. OBJECTIVE: Compare psychosocial profile of magnetically-controlled growing rod (MCGR) patients to traditional-growing rod (TGR) with an array of psychiatric tools, expecting improvement in MCGR due to decreased number of surgical procedures. SUMMARY OF BACKGROUND DATA: TGR treatment has had positive clinical and radiographic results; however, upward of 10 surgical sessions and high complication rates have called into question the quality of life of these children. Improvement with the introduction of the MCGR is expected. METHODS: GR patients with minimum of 2-years follow-up were recruited. None had neurological conditions. All underwent testing with the Wechsler Intelligence Scale for Children-Revised, and only those in the normal range were included. Patients filled out questionnaires with mental health professionals to measure psychosocial status. MCGR patients' results were compared to TGR patients. RESULTS: Twenty-seven patients met criteria (10 MCGR, 17 TGR): average age at enrollment 11.8 years (range 5.9-17). MCGR group was significantly younger (9.1 vs. 13.3 yr) and had significantly shorter follow-up (45.6 vs. 82.8 mo) (P < 0.05). TGR patients underwent an average of 16 surgical procedures, MCGR an average of 1.5 (including complications, P < 0.05). Age at index surgery (6 yr), preoperative and postoperative major curve magnitudes (60°, 40° respectively) were statistically similar.There was no difference in current psychiatric diagnoses between the groups. MCGR patients scored worse than TGR patients in general functionality domains. TGR patients showed increased functionality and prosocial scores with increased number of procedures. This effect was not observed in MCGR. CONCLUSIONS: The expected improvement in psychosocial status with the MCGR was not observed at a 31.6-month-follow-up. It appears that provided the patient spends enough time in the treatment process to notice benefit and does not experience major complications, noninvasiveness of lengthening procedures does not show up as an advantage with the psychosocial tools utilized in this study. LEVEL OF EVIDENCE: 3.

Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate - New Perspectives in Regenerative Medicine Arising from an Underestimated Tool.

Tissue engineering and stem cell-based therapies are one of the most rapidly developing fields in medical sciences. Therefore, much attention has been paid to the development of new drug-delivery systems characterized by low cytotoxicity, high efficiency and controlled release. One of the possible strategies to achieve these goals is the application of magnetic field and/or magnetic nanoparticles, which have been shown to exert a wide range of effects on cellular metabolism. Static magnetic field (SMF) has been commonly used in medicine as a tool to increase wound healing, bone regeneration and as a component of magnetic resonance technique. However, recent data shed light on deeper mechanism of SMF action on physiological properties of different cell populations, including stem cells. In the present review, we focused on SMF effects on stem cell biology and its possible application as a tool for controlled drug delivery. We also highlighted the perspectives, in which SMF can be used in future therapies in tissue engineering due to its easy application and a wide range of possible effects on cells and organisms.

Complex Regional Pain Syndrome Type I, a Debilitating and Poorly Understood Syndrome. Possible Role for Pulsed Electromagnetic Fields: A Narrative Review.

BACKGROUND: Complex regional pain syndrome type I (CRPS-I), also called algodystrophy, is a complex syndrome characterized by limb pain, edema, allodynia, hyperalgesia and functional impairment of bone with a similar clinical picture of osteoporosis, including an increased release of various pro-inflammatory neuropeptides and cytokines. Several treatments have been proposed for CRPS-I, but due to the poor outcome of conventional drugs and the invasiveness of some techniques, expectations are now directed towards new resources that could be more effective and less invasive. OBJECTIVE: In the light of preclinical evidence, which underlined pulsed electromagnetic fields' (PEMFs) properties on osteoblasts (OBs), osteoclasts (OCs), and pathologies with an inflammatory profile, the present review aims to investigate whether there is a rationale for the use of PEMFs, as a combined approach, in CRPS-I. STUDY DESIGN: This review analyzed the 44 in vitro and in vivo studies published in the last decade that focused on 2 main aspects of CRPS-I: local osteoporosis (OP) and inflammation. SETTING: Not applicable. METHODS: This review includes in vitro and in vivo studies found with a PubMed and Web of Knowledge database search by 2 independent authors. The limits of the search were the publication date between January 1, 2006, and January 1, 2016, and English language. In detail, the search strategy was based on: 1) CRPS-I or algodystrophy; 2) OP, OCs, and OBs; and 3) inflammatory aspects. RESULTS: The included studies looked at the relationship between PEMFs and OCs (2 in vitro studies), osteoporotic animal models (8 in vivo studies), OBs (20 in vitro studies), inflammatory cytokines, and reactive oxygen species. They also tried to define the molecular cell pathways involved (5 in vivo and 9 in vitro studies on inflammatory models). It was observed that PEMFs increased OC apoptosis, OB viability, bone protein and matrix calcification, antioxidant protein, and the levels of adenosine receptors, while it decreased the levels of pro-inflammatory cytokines. LIMITATIONS: Data from clinical trials are scarce; moreover, experimental conditions and PEMF parameters are not standardized. CONCLUSIONS: The present review underlined the rationale for the use of PEMFs in the complex contest of CRPS-I syndrome, in combination with conventional drugs. Key words: Complex regional pain syndrome type I, algodystrophy, pulsed electromagnetic field stimulation, osteoporosis, inflammation, osteoclasts, osteoblasts, pain.

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

[The potential of general magnetic therapy for the treatment and rehabilitation (a review)].

This paper was designed to describe the main characteristics of general magnetic therapy and the mechanisms underlying its biological and therapeutic action. Special attention is given to the extensive application of this method in the routine clinical practice. The publications in the current scientific literature are reviewed in order to evaluate the potential of general magnetic therapy as a component of the combined treatment of various somatic pathologies, rehabilitation of the patients after surgical intervention with special reference to the management of the patients presenting with the oncological problems. The data suggesting good tolerability and high therapeutic effectiveness of the physiotherapeutic method under consideration.

The emerging applications of magnetic nanovectors in nanomedicine.

The scientific disciplines that encompass medical therapy and diagnostics, in a continuing transition to personalized medicine, have found a valuable tool in the emerging field of nanotechnology. New nanotools are now enabling discoveries and advancements that form the foundation of what has become known collectively as nanomedicine. The global impact of these advancements are being seen in areas of advanced/improved early stage diagnostics, targeted drug delivery systems and imaging methods, all leading to more effective diagnostic/therapeutic strategies and outcomes. This review focuses on recent patent advancements in this transition with emphasis on the emerging role of magnetic nanovectors as enabling tools for the enhanced effectiveness of cancer diagnostics and therapeutics, considering its historical progression and future impact.

Local ELF-magnetic field: a possible novel therapeutic approach to psychology symptoms.

The recorded EEG of some brain regions of patients such as attention deficit hyperactivity disorder (ADHD), depression and etc. are different in comparison to healthy people. The disease improves with modifying the patient EEG that this is the basis of neurofeedback training. The main disadvantage of neurofeedback training demands patient's collaborative and active participation during treatment sessions, while some of patients such as addicts, depressed people and ADHD children cannot easily concentrate in direction of therapist's purpose. Furthermore, extremely low frequency magnetic fields (MFs) can affect brain signals and change them that in some cases lead to clinical effects. This report proposes if by locating small coils in desired region proceeds to local exposure of brain and happens in different frequencies or intensities and the effects of each MF in brain signals get analyzed then by knowing its effects we can make changes in patient voluntary without direct participation of patient in his/her brain signal changes. In the other words by changing type of the MF exposure and immediate record of brain signals we can fallow brain signals by observing the immediate record after exposure, with changes in the amplitude and the next exposure frequency, the therapist tries to direct the brain signal of desired region to the purpose. The possibility of approving this hypothesis in spite of contradictory effects about recovery or appearance of depression because of the MF and ability of local magnetic field exposures in changing of brain signals get reinforced to some extent.

Non-invasive brain stimulation in neurological diseases.

Non-invasive brain stimulation has shown its potential to modulate brain plasticity in humans. Endeavour has been made to utilize brain stimulation in neurological diseases to enhance adaptive processes and prevent potential maladaptive ones. In stroke for instance both sensorimotor and higher cognitive impairment, such as aphasia and neglect, has been addressed to facilitate functional recovery. In Parkinson's disease, brain stimulation has been evaluated to improve motor and non-motor symptoms. In the present review we provide an update of the field of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) as non-invasive brain stimulation techniques to improve motor and higher cognitive functions in patients suffering from stroke and Parkinson's disease. Rather than attempting to be comprehensive in regard of the reviewed scientific field, this article may be considered as a present day's framework of the application of non-invasive brain stimulation on selected examples of common neurological diseases. At the end we will briefly discuss open controversies and future directions of the field which has to be addressed in upcoming studies. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Nanotechnology advances in upper gastrointestinal, liver and pancreatic cancer.

Cancers of the upper GI tract, liver and pancreas have some of the poorest prognoses of any malignancies. Advances in diagnosis and treatment are sorely needed to improve the outcomes of patients. Nanotechnology offers the potential for constructing tailor-made therapies capable of targeting specific cancers. The particles themselves may be endowed with multifunctional properties that can be exploited for both diagnosis and treatment. Although development of therapies is still in the early stages, the use of nanoparticles (NPs) is widespread in diagnostic applications and will probably involve all areas of medicine in the future. Research into NPs is ongoing for upper gastrointestinal, liver and pancreatic cancers, and their use is becoming increasingly popular as contrast media for radiological investigations. Although more sophisticated technologies capable of active targeting are still in the early stages of assessment for clinical use, a small number of NP-based therapies are in clinical use.

Analisis poblacional del uso y eficiencia de los soportes plantares imantados / Population analysis use and efficiency orthotics magnetized

Todos los seres vivos se encuentran bajo la influencia de un campo magnético. Por esta afirmación han sido utilizados los dispositivos magnéticos en diversas patologías para aliviar la sintomatología. El objetivo del estudio es realizar una revisión de la literatura publicada acerca del tratamiento de diversas patologías mediante el uso de dispositivos imantados, principalmente el de los soportes plantares. Se diseña una encuesta (N=60) acerca del conocimiento poblacional sobre estos dispositivos. Los resultados obtenidos en las encuestas demuestran un escaso conocimiento de los dispositivos y poca creencia en los mismos. La revisión de la literatura pone de manifiesto que este tipo de tratamiento con imanes posee un gran componente placebo(AU)

All living beings are under the influence of a magnetic field. By this statement the magnetic devices in various pathologies have been used to relieve the symptoms. The objective of the study is to conduct a review of published literature on the treatment of various diseases using magnetic devices, mainly of magnetic insoles. Designing a survey (N = 60) of population knowledge on these devices. The results obtained in the surveys show a little knowledge of devices and little belief in them. The literature review shows that this type of treatment with magnets has a large placebo component(AU)

[Applications of magnetic stimulation in biomedicine].

Magnetic stimulation as an efficient and non-invasive technique has been applied broadly in clinical practice. It is mostly used in determination of nerve centre motor conduct and evaluation of motor cortex excitability; in inspection of central nervous system function by measuring peripheral nerve conduct; and in study of pallium nerve distribution. These are conducted in an attempt to control brain activity and provide new methods for the diagnosis and treatment of some brain diseases. This paper reviews the physical theory and functional mechanism of magnetic stimulation, as well as the applications of magnetic stimulation in biomedical examination and treatment.