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.

The bioenergetics of COVID-19 immunopathology and the therapeutic potential of biophysical radiances.

In developing an effective clinical tool against COVID-19, we need to consider why SARS-CoV-2 infections develop along remarkably different trajectories: from completely asymptomatic to a severe course of disease. In this paper we hypothesize that the progressive exhaustion and loss of lymphocytes associated with severe stages of COVID-19 result from an intracellular energy deficit in an organism which has already been depleted by preexisting chronic diseases, acute psychological stress and the aging process. A bioenergetics view of COVID-19 immunopathology opens a new biophysical opportunity to enhance impaired immune function via proposed pathways of photomagnetic catalysis of ATP synthesis, regenerative photobiomodulation and the ultrasonic acceleration of cell restructuring. Moreover, we suggest that a coherent application of multiple biophysical radiances (coMra) may synergistically enhance energy-matter-information kinetics of basal self-regeneration of cells and thus improve immune function and accelerate recovery.

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.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

The Future of Brain Stimulation Treatments.

Trends in brain stimulation include becoming less invasive, more focal, and more durable with less toxicity. Several of the more interesting new potentially disruptive technologies that are just making their way through basic and sometimes clinical research studies include low-intensity focused ultrasound and temporally interfering electric fields. It is possible, and even likely, that noninvasive brain stimulation may become the dominant form of brain treatments over the next 20 years. The future of brain stimulation therapeutics is bright.

Evolution of Comprehensive Care, Part 3. Periodontal Treatment Continues to Evolve.

Perio treatment has evolved beyond simple scaling with hand instruments. Ultrasonics and diode lasers have improved both the efficiency of treatment as well as treatment prognosis to arresting the disease process and gaining clinical attachment and decreasing pocket depth. Add to this the benefits of adjunct medicaments both at time of treatment via site placement and during routine home care by the patient, and we are able to tip treatment outcome in a more favorable direction. Periodontology has been closely linked to systemic health both as a causative agent to health issues and as a secondary site for some medical conditions. Dentistry has truly--and finally--become a part of total healthcare.

Ultrasound-guided therapeutic focused ultrasound: current status and future directions.

This paper reviews ultrasound imaging methods for the guidance of therapeutic focused ultrasound (USgFUS), with emphasis on real-time preclinical methods. Guidance is interpreted in the broadest sense to include pretreatment planning, siting of the FUS focus, real-time monitoring of FUS-tissue interactions, and real-time control of exposure and damage assessment. The paper begins with an overview and brief historical background of the early methods used for monitoring FUS-tissue interactions. Current imaging methods are described, and discussed in terms of sensitivity and specificity of the localisation of the FUS effects in both therapeutic and sub-therapeutic modes. Thermal and non-thermal effects are considered. These include cavitation-enhanced heating, tissue water boiling and cavitation. Where appropriate, USgFUS methods are compared with similar methods implemented using other guidance modalities, e.g. magnetic resonance imaging. Conclusions are drawn regarding the clinical potential of the various guidance methods, and the feasibility and current status of real-time implementation.

Overview of non-invasive factors (low level laser and low intensity pulsed ultrasound) accelerating tooth movement during orthodontic treatment.

The need for orthodontic treatment is increasing all the time. As the treatment is time consuming ranging from a year to several years, any method of reducing the period of treatment and increasing the quality of the tissue will be beneficial to patients. The use of non-invasive techniques such as low level laser therapy and low intensity pulsed ultasound in accelerating orthodontic tooth movement are promising. Thus, this overview study will help to generate more understanding about the background information and the possible applications of them in daily orthodontics, depending on previous literature searching for reviews and original research articles.

[Development of studies on bioeffects of ultrasound-acupuncture therapy and its underlying mechanism].

The so-called ultrasound acupuncture is a therapeutic approach for clinical problems and health care by applying the ultrasound energy to the acupoints of the human body directly or indirectly. It has been applied in clinic for about 30 years since 1980s. In the present paper, the authors review the development of both experimental and clinical researches in the past 30 years. Its clinical application includes allergic rhinitis, local pain, mastitis, angina pectoris of coronary heart disease, stroke, etc. Regarding the researches on the underlying mechanism of ultrasound and ultrasound acupuncture, the authors make a summary from 1) bioeffects (thermal and nonthermal effects) of ultrasound intervention; 2) cell lysis and nonlysis effects of ultrasound intervention; and 3) effects of ultrasound acupuncture on the degranulation of mast cells. Based on the idea that "inflammatory reaction caused by mast cell degranulation is one of the initial factors of acupuncture for inducing therapeutic effects", bioeffects including cellular changes, especially mast cell degranulation caused by ultrasound stimulation, are thought to be the main possible mechanisms underlying the favorable efficacy of ultrasound acupuncture intervention. However, the ultrasound metrology and the specific superiority of ultrasound acupuncture remain unknown up to now.

Emerging bone healing therapies.

Fracture healing is a biologically optimized process. Despite the expectation of unimpaired healing, approximately 5% to 10% of the 7.9 million fractures sustained annually in the United States have difficulty achieving union. Not only does this cause morbidity for patients, but also enormous healthcare and socioeconomic costs. Hence, there is a compelling need to find novel therapies to enhance fracture healing. In this article, we summarize current data on therapies to enhance skeletal healing and review their suggested biologic functions, proposed clinical applications, and known efficacies.

Sonothrombolysis: experimental evidence.

Reopening of the occluded artery is the primary therapeutic goal in hyperacute ischemic stroke. Systemic treatment with tissue recombinant plasminogen activator (tPA) has been shown to be beneficial at least in a 3-hour door to needle window. Intra-arterial thrombolysis is favorable and opens the window of treatment up to at least 6 h but consequences invasive intra-arterial angiography in a high number of patients, of whom a significant number do not finally receive thrombolysis. The combination of ultrasound with thrombolytic agents may enhance the potential benefit by means of enzyme-mediated thrombolysis. When ultrasound is applied externally through skin or chest, attenuation will be very low. Attenuation, however, is significantly higher if penetration through the skull is required. Attenuation is frequency dependent, with ultrasound intensity being <10% of the output intensity for diagnostic frequencies (>1 MHz). This ratio nearly reverses in the kiloHertz range (>500 kHz). Ultrasound insonation is efficient for accelerating enzymatic thrombolysis within a wide range of intensities, from 0.5W/cm2 (MI approximately 0.3) to several watts per square centimeter, particularly in the nonfocused ultrasound field. Insonation with ultrasound increased tPA-mediated thrombolysis up to 20% in a static model, while it enhanced the recanalization rate from 30 to 90% in a flow model. Results from embolic rat models suggest that low-frequency ultrasound with 0.6W/cm2 significantly reduces infarct volume compared to pure tPA treatment. Safety of ultrasound exposure of the brain for therapeutic purposes has to address hemorrhage, heating, and direct tissue damage. Since animal studies suggested no increase of bleeding rate or harm to the blood-brain barrier, a clinical phase II study applying low-frequency ultrasound at approximately 300 kHz found a high number of secondary hemorrhages. Heating depends critically on the characteristics of the ultrasound. The most significant heating of the brain tissue itself is >1 degrees C per hour using a 2W/cm2 probe; however, no significant heating could be found when using an emission protocol pulsing the ultrasound. The current experimental data helps to identify the optimal ultrasound characteristics for sonothrombolysis and supports the hypothesis combined treatment being a perspective in optimizing thrombolytic therapy in acute stroke.

Power scalers: the new boom in contemporary periodontics.

The choice of which type of instrumentation to use remains the decision of the practitioner. It all depends on what goal the clinician hopes to achieve, the resources, and the physical set up within which they work. While speed in debridement, coupled with ease of use and comfort to the patient and practitioner are all important, the primary goal must always remain the optimal healing and success of the dental procedure. With improved tip designs and efficiency, power scaling has the ability to improve dental hygiene and periodontal care in the future.

[Recent progress of thermoradiotherapy in cancer therapy].

The recent progress of thermoradiotherapy for cancer is reviewed. Several biological methods for increasing the effects of heat on tumors have been developed, and some of them are being clinically investigated. Physical progress includes two new heating devices developed in Japan. One is an ultrasound heating system and the other is an intracavitary RF heating applicator in which simultaneous intracavitary irradiation is possible. The negative results of RTOG trial in USA caused a great impact in clinical hyperthermia. Careful analysis of this trial, however, demonstrated the advantages of the use of hyperthermia for those cases in which ther was good quality assurance of hyperthermia. Recent results of ESHO trials in Europe clearly demonstrated the superiority of thermoradiotherapy over radiotherapy alone for several tumors. Various site-specific clinical trials are expected to clarify the indications of thermoradiotherapy in future.