PEMF Mat

PEMF Therapy with Infrared

Military, Veteran or Health Condition?

You Qualify for a discount! See Here

Frequently Asked Questions

What is PEMF and how does it work?

PEMF (Pulsed Electromagnetic Field) sends beneficial low frequency electromagnetic waves through your body interacting with electrolytes and ions to help promote your body’s own recovery process.


These EMFs (Electromagnetic Fields) are different from those found in devices like x-ray machines, microwaves, 5g and other every day appliances due to their specific frequency. PEMF waves are also delivered in small bursts, mimicking the same kind of electromagnetic waves generated by the planet naturally.


The PEMF (Pulsed Electromagnetic Field) technology used in the Revie is fully adjustable so you can tune frequency for different goals and purposes; We have also added Far Infrared Therapy and Red Light Therapy.

Who should use this device?

The Revive PEMF Mat is literally for everybody. Whether you deal with chronic pain, enjoy working out, or are looking to activate your parasympathetic nervous system, lying on the Mat for even a couple of minutes a day (or whenever you need it) will help support countless benefits at a cellular level and improve your overall wellness.

Is PEMF Safe?

Yes! Our product page links to many, many medical journals. If you review them you will see for yourself that there are no reported negative side effects of PEMF therapy.


The FDA has approved PEMF for a variety of different treatments, and research on the efficacy of PEMF continues to be produced.


Of course, as always, we want to make it clear we are not medical professionals. Even with mountains of medical research, it’s always wise to consult your doctor prior to adding in new therapies. Especially if you have medications or pre-existing conditions.

Is PEMF a New Technology?

Oddly enough, no, not really. It came into use back in the early 1970’s and was first used by veterinarians to speed the healing of bone fractures in race horses.


NASA even adopted it to be used in its space program, helping Astronauts continue to receive the natural electromagnetic fields and pulse of the planet while traveling in space for easy re-assimilation on return to earth.


Since, there are a multitude of symptoms and conditions which PEMF is being used and experimented with for treatment.

Product Specifications

Potential Benefits Include:

Reduced Stress

Increased Energy

Better Sleep

Improved Immune Response

Improved Circulation

Improved Muscle Recovery & Growth

Improved Overall Wellness


Size: 39” x 19.5”

Weight: 12.5lbs

Power: Voltage 120V. Wattage 125W

PEMF Info: 3pcs PEMF Devices Implanted. Adjustable Frequency 1-40 hz. 50-100 Gauss while operating.

Heaters: Zero EMF Far Infrared; 10,000 Strand Carbon Fiber with Faraday System

Red Light: 12 Food Grade Silica LED Photon Lights tuned to 660nm wavelength

Free 45 Day Trial

Not Satisfied? Get your money back

Free 2-5 Day Shipping

Express Shipping Across the U.S.

PEMF & Infrared Mat

PEMF Therapy with Red Light & Far Infrared

  • HEAL NATURALLY – Low Frequency PEMF penetrate & stimulate tissue, organs, and bones at a cellular level... boosting electrical and chemical processes which enhances Your body’s natural recovery process 

  • DECREASE STRESS – experience Alpha and Theta Waves that promote a trans-like state and mimic subconscious brainwaves

  • BOOST MOOD – improve glucose metabolism in the brain and train it with rhythms that mimic rest to support decreased depression and anxiety

  • RELIEVE CHRONIC PAIN – From Bone and joint disorders to neuropathic pain, PEMF, Red Light Therapy and Infrared is scientifically shown to reduce pain reception

  • OPTIMIZE yOUR BODY – Increase circulation & oxygenation, gain a more robust immune response, reduce inflammation and oxidative stress

  • PRE SET PROGRAMS – one of the only Brands offering 14 separate programs to make sessions quick easy set it and forget its!

$599.99

The HEALiX Revive Mini brings together three of the most risk free and prominent holistic healing technologies to create the Ultimate Trifecta. 

 

The Revive PEMF Mat takes our expertly engineered Infrared Technology and combines it with PEMF & Red Light Therapy to provide you with a combination that enhances the benefits of one another. 

 

What is it? Pulsed Electromagnetic Frequency - PEMF Therapy uses low frequency, beneficial, pulsed magnetic fields clinically shown to produce health-giving effects ranging from healing and strengthening bones, to activating your parasympathetic nervous system, even slowing the growth of certain cancer cells.

 

The Revive PEMF Mat is one of a few available on the market which is fully adjustable from 1-30hz.  This allows you to tune your PEMF to the appropriate frequency for your individual health goals.

 

Add all of that to the well-established and scientifically proven benefits of Far Infrared and Red Light Therapy and you are sure to be blown away by the soothing heat healing experience of the HEALiX Revive.

Military, Veteran or Health Condition?

You Qualify for a discount! See Here
$599.99

Military, Veteran or Health Condition?

You Qualify for a discount! See Here

Free 2-5 Day Shipping

We Pick Up Cost For Express Shipping Across the Lower 48

45 Days Risk Free

Not Satisfied? Get in touch for your money back

$599.99

Frequently Asked Questions

What is PEMF and how does it work?

PEMF (Pulsed Electromagnetic Field) sends beneficial low frequency electromagnetic waves through your body interacting with electrolytes and ions to help promote your body’s own recovery process.


These EMFs (Electromagnetic Fields) are different from those found in devices like x-ray machines, microwaves, 5g and other every day appliances due to their specific frequency. PEMF waves are also delivered in small bursts, mimicking the same kind of electromagnetic waves generated by the planet naturally.


The PEMF (Pulsed Electromagnetic Field) technology used in the Revie is fully adjustable so you can tune frequency for different goals and purposes; We have also added Far Infrared Therapy and Red Light Therapy.

Who should use this device?

The Revive PEMF Mat is literally for everybody. Whether you deal with chronic pain, enjoy working out, or are looking to activate your parasympathetic nervous system, lying on the Mat for even a couple of minutes a day (or whenever you need it) will help support countless benefits at a cellular level and improve your overall wellness.

Is PEMF Safe?

Yes! Our product page links to many, many medical journals. If you review them you will see for yourself that there are no reported negative side effects of PEMF therapy.


The FDA has approved PEMF for a variety of different treatments, and research on the efficacy of PEMF continues to be produced.


Of course, as always, we want to make it clear we are not medical professionals. Even with mountains of medical research, it’s always wise to consult your doctor prior to adding in new therapies. Especially if you have medications or pre-existing conditions.

Is PEMF a New Technology?

Oddly enough, no, not really. It came into use back in the early 1970’s and was first used by veterinarians to speed the healing of bone fractures in race horses.


NASA even adopted it to be used in its space program, helping Astronauts continue to receive the natural electromagnetic fields and pulse of the planet while traveling in space for easy re-assimilation on return to earth.


Since, there are a multitude of symptoms and conditions which PEMF is being used and experimented with for treatment.

Product Specifications

Potential Benefits Include:

Reduced Stress

Increased Energy

Better Sleep

Improved Immune Response

Improved Circulation

Improved Muscle Recovery & Growth

Improved Overall Wellness


Size: 40” x 20”

Weight: 11lbs

Power: Voltage 120V. Wattage 150W

PEMF Info: 2pcs PEMF Devices Implanted. Adjustable Frequency 1-30 hz.

Heaters: Zero EMF Far Infrared; 10,000 Strand Carbon Fiber with Faraday System

Red Light: 6 Food Grade Silica LED Photon Lights tuned to 660nm wavelength

Military, Veteran or Health Condition?

You Qualify for a discount! See Here

What Everyone's feeling

sauna detox, personal sauna, portable sauna

Reduced

Stress & Anxiety

sauna detox, personal sauna, portable sauna

Improved

Sleep

sauna detox, personal sauna, portable sauna

Increased

Energy

infrared, reduce pain infrared, infrared for inflammation

Chronic Pain 

Relief

Revive Yourself On A Cellular Level

Recharge, Relax, Recover With PEMF

Alpha & Theta Waves Promote A Trancelike State & Support Sleep

Correct Cell Dysfunction + Reduce Growth Of Harmful Cells

Correct Inflammatory Response To Upgrade Your Immune System

Recharge Yourself With The Frequency Of Earth’s Magnetic Field

**HEALiX has not received brand specific FDA approval

Alpha & Theta Waves Promote A Trancelike State & Support Sleep

Recharge yourself With The Frequency Of Earth’s Magnetic Field

Correct Cell Dysfunction + Reduce Growth Of Harmful Cells

Correct Inflammatory response to Upgrade Your Immune System

explore pEMF's researched benefits

Red Light Therapy

Charge Cell Respiration, Blood Oxygen levels & More

Turbo charge

far infrared results

energize at a

cellular level

full body

inflammation reduction

Support

far infrared results

Improved

inflammation reduction

energize at a

cellular level

premium results from Synergy

low emf sauna blanket, zero emf infrared, sauna bag

PEMF Therapy

Low Frequency Magnetic 

Waves Charge Your Body's Natural Healing Abilities

low emf sauna blanket, zero emf infrared, sauna bag

Red Light Therapy

Boosts ATP, collagen + elastin and rejuvenates Absorption to Improve Skin Health

low emf sauna blanket, zero emf infrared, sauna bag

Far Infrared

calming heat Lowers 

inflammation & Supports Supreme circulation

low emf sauna blanket, zero emf infrared, sauna bag

Ionizing Stones

Gems Release Far Infrared & Negative Ions While improving pEMF, Infrared & Red Light Results

Superior ZERO EMF far Infrared

Superior

ZERO EMF

far Infrared

The Only Safe far infrared

increase

blood circulation

improve Your

sleep cycle

Activate Parasympathetic

Nervous System

increase

blood circulation

improve Your

sleep cycle

Activate Parasympathetic

Nervous System

unique to HEALiX

carbon fiber infrared, safe infrared, infrared blanket

Fully 

Adjustable PEMF 

Controllable Frequency 0-30Hz To Hit Your Personal Goals

low emf sauna blanket, zero emf infrared, sauna bag

Zero EMF

Far Infrared

Say Good Bye to The Bad Part of Infrared and only get benefits

easy clean up sauna, medical grade sauna blanket, portable sauna

Non-Toxic Silica

Photon LEDs

red light tuned to 660nm for Widest array of benefits

Red light therapy at home, infrared, infrared body wrap

Preset

Programs

Set it and forget it! We've already set up Therapy Sessions for you

carbon fiber infrared, safe infrared, infrared blanket

Fully 

Adjustable PEMF 

Controllable Frequency 0-30Hz To Hit Your Personal Goals

Red light therapy at home, infrared, infrared body wrap

Preset

Programs

Set it and forget it! We've already set up Therapy Sessions for you

easy clean up sauna, medical grade sauna blanket, portable sauna

Non-Toxic Silica

Photon LEDs

red light tuned to 660nm for Widest array of benefits

low emf sauna blanket, zero emf infrared, sauna bag

Zero EMF

Far Infrared

Say Good Bye to The Bad Part of Infrared and only get benefits

It's What's Inside That Matters...

Next Level Customer Experience

24 Month Warranty

Double Most Of Our Competitors

45 Day Trial

Cause We Know You'll Love It

Fitness, Psych & Nutrition Staff

Everything You Need For A Well Rounded You

See What Everyone Is Saying

Your Body Is Capable Of More

Our Mission Is To Have You Realize & Capitalize That!

Half An Entire Lifetime. That is how long I've dedicated to learning about Holistic Nutrition, Physical Fitness, Mental Health & General Wellness.  As a Psychologist & Trainer, I have held licenses for over 10 years.

After working with countless clients there is one thing that is consistent: People doubt what their body and mind are capable of.  


The human body is resilient and strong, even in times of weakness.  Time and time again, I watched those struggling provide their body and mind with basic supports.  Soon, finding amazement in how they transformed.


Our mission here is for you to become one of those many people.  Infrared is a simple, work and stress free support.  You can give yourself better wellness and find longer, higher quality life.  Even if infrared is not for you, follow us for tips, information and motivation to find your full potential!

Founder & Team Member

We're Serious About Our Goals To Help EVERYONE Take A Step Towards Better Wellness

So we’re trying to make infrared more accessible to those in need.  Many of our customers are Ex-Military and/or Disabled.


We have direct family members both actively serving and who are now veterans. We are thankful for those who make the sacrifices that come along with service and want to support them.


We also have family close to us battling autoimmune disease which causes chronic inflammation and pain, and have seen relief from taking action.


If you can send us a quick message or email with proof of military service or diagnosed medical condition, we will send you a personal code, good for a $30 discount.

Impact of pulsed electromagnetic field therapy on vascular function and blood pressure in hypertensive individuals

Abstract


The present study investigated the impact of 12 weeks of pulsed electromagnetic field (PEMF) therapy on peripheral vascular function, blood pressure (BP), and nitric oxide in hypertensive individuals. Thirty hypertensive individuals (SBP > 130 mm Hg and/or MAP > 100 mm Hg) were assigned to either PEMF group (n = 15) or control group (n = 15). During pre‐assessment, participants underwent measures of flow‐mediated dilation (FMD), BP, and blood draw for nitric oxide (NO). Subsequently, they received PEMF therapy 3x/day for 12 weeks and, at conclusion, returned to the laboratory for post‐assessment. Fifteen participants from the PEMF group and 11 participants from the control group successfully completed the study protocol. After therapy, the PEMF group demonstrated significant improvements in FMD and FMDNOR (normalized to hyperemia), but the control group did not (P = .05 and P = .04, respectively). Moreover, SBP, DBP, and MAP were reduced, but the control group did not (P = .04, .04, and .03, respectively). There were no significant alterations in NO in both groups (P > .05). Twelve weeks of PEMF therapy may improve BP and vascular function in hypertensive individuals. Additional studies are needed to identify the mechanisms by which PEMF affects endothelial function.

Cited:

Stewart GM, Wheatley-Guy CM, Johnson BD, Shen WK, Kim CH. Impact of pulsed electromagnetic field therapy on vascular function and blood pressure in hypertensive individuals. J Clin Hypertens (Greenwich). 2020 Jun;22(6):1083-1089. doi: 10.1111/jch.13877. Epub 2020 May 13. PMID: 32401418; PMCID: PMC8030044.

Your Body Is Capable Of More

Our Mission Is To Have You Realize & Capitalize That!

Half An Entire Lifetime. That is how long I've dedicated to learning about Holistic Nutrition, Physical Fitness, Mental Health & General Wellness.  As a Psychologist & Trainer, I have held licenses for over 10 years.

After working with countless clients there is one thing that is consistent: People doubt what their body and mind are capable of.  


The human body is resilient and strong, even in times of weakness.  Time and time again, I watched those struggling provide their body and mind with basic supports.  Soon, finding amazement in how they transformed.


Our mission here is for you to become one of those many people.  Infrared is a simple, work and stress free support.  You can give yourself better wellness and find longer, higher quality life.  Even if infrared is not for you, follow us for tips, information and motivation to find your full potential!

Founder & Team Member

Resource Cited:

Kıvrak EG, Yurt KK, Kaplan AA, Alkan I, Altun G. Effects of electromagnetic fields exposure on the antioxidant defense system. J Microsc Ultrastruct. 2017 Oct-Dec;5(4):167-176. doi: 10.1016/j.jmau.2017.07.003. Epub 2017 Aug 2. PMID: 30023251; PMCID: PMC6025786.

**HEALiX has not received brand specific FDA approval

Pulsed Electromagnetic Fields Increased the Anti-Inflammatory Effect of A2A and A3 Adenosine Receptors in Human T/C-28a2 Chondrocytes and hFOB 1.19 Osteoblasts

Abstract


Adenosine receptors (ARs) have an important role in the regulation of inflammation and their activation is involved in the inhibition of pro-inflammatory cytokine release. The effects of pulsed electromagnetic fields (PEMFs) on inflammation have been reported and we have demonstrated that PEMFs increased A2A and A3AR density and functionality in different cell lines. Chondrocytes and osteoblasts are two key cell types in the skeletal system that play important role in cartilage and bone metabolism representing an interesting target to study the effect of PEMFs. The primary aim of the present study was to evaluate if PEMF exposure potentiated the anti-inflammatory effect of A2A and/or A3ARs in T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. Immunofluorescence, mRNA analysis and saturation binding assays revealed that PEMF exposure up-regulated A2A and A3AR expression. A2A and A3ARs were able to modulate cAMP production and cell proliferation. The activation of A2A and A3ARs resulted in the decrease of some of the most relevant pro-inflammatory cytokine release such as interleukin (IL)-6 and IL-8, following the treatment with IL-1β as an inflammatory stimuli. In human chondrocyte and osteoblast cell lines, the inhibitory effect of A2A and A3AR stimulation on the release of prostaglandin E2 (PGE2), an important lipid inflammatory mediator, was observed. In addition, in T/C-28a2 cells, the activation of A2A or A3ARs elicited an inhibition of vascular endothelial growth factor (VEGF) secretion. In hFOB 1.19 osteoblasts, PEMF exposure determined an increase of osteoprotegerin (OPG) production. The effect of the A2A or A3AR agonists in the examined cells was enhanced in the presence of PEMFs and completely blocked by using well-known selective antagonists. These results demonstrated that PEMF exposure significantly increase the anti-inflammatory effect of A2A or A3ARs suggesting their potential therapeutic use in the therapy of inflammatory bone and joint disorders.

Cited:

Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, Cadossi R, Goldring MB, Borea PA, Varani K. Pulsed electromagnetic fields increased the anti-inflammatory effect of A₂A and A₃ adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One. 2013 May 31;8(5):e65561. doi: 10.1371/journal.pone.0065561. PMID: 23741498; PMCID: PMC3669296.

High-intensity laser therapy versus pulsed electromagnetic field in the treatment of primary dysmenorrhea

Abstract


[Purpose] To determine the efficacy of high intensity laser therapy (HILT) versus pulsed electromagnetic field (PEMF) in the treatment of primary dysmenorrhea. [Subjects and Methods] This was a randomized clinical trial that included 52 girls diagnosed with primary dysmenorrhea and who were assigned randomly into two groups of equal numbers. The treatment was three sessions every cycle for three consecutive cycles where group (A) included those participants treated with HILT 15 min/session and group (B) those who were treated with PEMF 30 min/session. All patients were evaluated before starting the treatment as well as after the end of treatment by present pain intensity scale and the prostaglandin level in blood and pain relief scale at the end of treatment for both groups. [Results] The results showed a significant decrease in the severity of pain, statistically significant decrease in prostaglandin level in blood, and a statistically significant pain alleviation in both groups. With comparison between both groups there was a statistically significant decrease in the severity of pain, significant decrease in the blood levels of PGF2α, in group (A) than group (B). [Conclusion] Both HILT and PEMF are effective in the treatment of primary dysmenorrhea with HILT being superior to PEMF.

Cited:

Thabet AAE, Elsodany AM, Battecha KH, Alshehri MA, Refaat B. High-intensity laser therapy versus pulsed electromagnetic field in the treatment of primary dysmenorrhea. J Phys Ther Sci. 2017 Oct;29(10):1742-1748. doi: 10.1589/jpts.29.1742. Epub 2017 Oct 21. PMID: 29184281; PMCID: PMC5684002.

Effect of extremely low frequency electromagnetic field parameters on the proliferation of human breast cancer

Abstract


Extremely low-frequency electromagnetic field (ELF-EMF) exposures influence many biological systems. These effects are mainly related to the intensity, duration, frequency, and pattern of the ELF-EMF. Our intent was to characterize the effect of specific pulsed electromagnetic fields on the in vitro proliferation of MCF-7 adenocarcinoma and MDA-MB-231 breast cancer cell lines and one non-cancerous M10 breast epithelial cell line. The following four important parameters of ELF-EMF were examined: frequencies (7.83 ± 0.3, 23.49 ± 0.3, and 39.15 ± 0.3 Hz), flux density (0.5 and 1 mT), exposure duration (12, 24, and 48 h), and the exposure methodology (continuous exposure versus switching exposure). The viability of MDA-MB-231 cells exposed to the optimized ELF-EMF pattern (7.83 ± 0.3 Hz, 1 mT, and 6 h switching exposure) was 40.1%. By contrast, the optimized ELF-EMF parameters that were most cytotoxic to breast cancer MDA-MB-231 cells were not damaging to normal M10 cells. In vitro studies also showed that exposure of MDA-MB-231 cells to the optimized ELF-EMF pattern promoted Ca2+ influx and resulted in apoptosis. These data confirm that exposure to this specific ELF-EMF pattern can influence cellular processes and inhibit cancer cell growth. The specific ELF-EMF pattern determined in this study may provide a potential anti-cancer treatment in the future.

Cited:

Wang MH, Chen KW, Ni DX, Fang HJ, Jang LS, Chen CH. Effect of extremely low frequency electromagnetic field parameters on the proliferation of human breast cancer. Electromagn Biol Med. 2021 Jul 3;40(3):384-392. doi: 10.1080/15368378.2021.1891093. Epub 2021 Feb 25. PMID: 33632057.

Low frequency pulsed electromagnetic field--a viable alternative therapy for arthritis

Abstract


Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts anti-inflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.

Cited:

Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R. Low frequency pulsed electromagnetic field--a viable alternative therapy for arthritis. Indian J Exp Biol. 2009 Dec;47(12):939-48. PMID: 20329696.

Effects of pulsed electromagnetic field therapy on delayed-onset muscle soreness in biceps brachii

Abstract


Objective: to compare the effects of pulsed electromagnetic field (PEMF) therapy and sham treatment on DOMS-related variables in elbow flexors at 24, 48 and 72 h after delayed onset muscle soreness (DOMS) induction exercise.


Design: randomized, double-blind, placebo-controlled study.

Setting: Yonsei University laboratory.


Participants: In total, 30 healthy male college students.

Main outcome measures: Muscle soreness, peak torque, median frequency (MDF) and electromechanical delay (EMD) during isometric contraction at 24, 48 and 72 h after DOMS induction exercise.


Results: Overall, the application of the PEMF was found to be effective in reducing the physiological deficits associated with DOMS, including improved recovery of perceived muscle soreness, MDF, and EMD during isometric contraction. Our results did not show that PEMF treatment was mechanically more effective for isometric peak torque generation compared to the sham group.


Conclusion: this study indicates that PEMF may be useful as a modality to reduce DOMS symptoms. However, further well-designed experiments are required to determine optimal treatment dosage and duration, and to investigate the physiological and clinical mechanisms of PEMF on DOMS.

Cited:

Jeon HS, Kang SY, Park JH, Lee HS. Effects of pulsed electromagnetic field therapy on delayed-onset muscle soreness in biceps brachii. Phys Ther Sport. 2015 Feb;16(1):34-9. doi: 10.1016/j.ptsp.2014.02.006. Epub 2014 Mar 7. PMID: 24906295.

Low-Frequency Pulsed Electromagnetic Field Is Able to Modulate miRNAs in an Experimental Cell Model of Alzheimer's Disease

Abstract


The aim of the present study was to investigate on the effects of a low-frequency pulsed electromagnetic field (LF-PEMF) in an experimental cell model of Alzheimer's disease (AD) to assess new therapies that counteract neurodegeneration. In recent scientific literature, it is documented that the deep brain stimulation via electromagnetic fields (EMFs) modulates the neurophysiological activity of the pathological circuits and produces clinical benefits in AD patients. EMFs are applied for tissue regeneration because of their ability to stimulate cell proliferation and immune functions via the HSP70 protein family. However, the effects of EMFs are still controversial and further investigations are required. Our results demonstrate the ability of our LF-PEMF to modulate gene expression in cell functions that are dysregulated in AD (i.e., BACE1) and that these effects can be modulated with different treatment conditions. Of relevance, we will focus on miRNAs regulating the pathways involved in brain degenerative disorders.

Cited:

Capelli E, Torrisi F, Venturini L, Granato M, Fassina L, Lupo GFD, Ricevuti G. Low-Frequency Pulsed Electromagnetic Field Is Able to Modulate miRNAs in an Experimental Cell Model of Alzheimer's Disease. J Healthc Eng. 2017;2017:2530270. doi: 10.1155/2017/2530270. Epub 2017 May 2. PMID: 29065581; PMCID: PMC5434238.

Bone density changes in osteoporosis-prone women exposed to pulsed electromagnetic fields (PEMFs)

Abstract


To determine the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of osteoporosis-prone women, the nondominant forearms of 20 subjects were exposed to PEMF 10 h daily for a period of 12 weeks. Bone density before, during, and after the exposure period was determined by use of a Norland-Cameron bone mineral analyzer. Bone mineral densities of the treated radii measured by single-photon densitometry increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. A similar but weaker response occurred in the opposite arm, suggesting a "cross-talk" effect on the nontreated radii, from either possible arm proximity during sleep or very weak general field effects. The data suggest that properly applied PEMFs, if scaled for whole-body use, may have clinical application in the prevention and treatment of osteoporosis.

Cited:

Tabrah F, Hoffmeier M, Gilbert F Jr, Batkin S, Bassett CA. Bone density changes in osteoporosis-prone women exposed to pulsed electromagnetic fields (PEMFs). J Bone Miner Res. 1990 May;5(5):437-42. doi: 10.1002/jbmr.5650050504. PMID: 2195843.

Pulsed electromagnetic field therapy of persistent rotator cuff tendinitis. A double-blind controlled assessment

Abstract


The value of pulsed electromagnetic fields (PEMF) for the treatment of persistent rotator cuff tendinitis was tested in a double-blind controlled study in 29 patients whose symptoms were refractory to steroid injection and other conventional conservative measures. The treated group (15 patients) had a significant benefit compared with the control group (14 patients) during the first 4 weeks of the study, when the control group received a placebo. In the second 4 weeks, when all patients were on active coils, no significant differences were noted between the groups. This lack of difference persisted over the third phase, when neither group received any treatment for 8 weeks. At the end of the study 19 (65%) of the 29 patients were symptomless and 5 others much improved. PEMF therapy may thus be useful in the treatment of severe and persistent rotator cuff and possibly other chronic tendon lesions.

Cited:

Binder A, Parr G, Hazleman B, Fitton-Jackson S. Pulsed electromagnetic field therapy of persistent rotator cuff tendinitis. A double-blind controlled assessment. Lancet. 1984 Mar 31;1(8379):695-8. doi: 10.1016/s0140-6736(84)92219-0. PMID: 6143039.

Regulation of skin collagen metabolism in vitro using a pulsed 660 nm LED light source: clinical correlation with a single-blinded study

Abstract


It has been reported that skin aging is associated with a downregulation in collagen synthesis and an elevation in matrix metalloproteinase (MMP) expression. This study investigated the potential of light-emitting diode (LED) treatments with a 660 nm sequentially pulsed illumination formula in the photobiomodulation of these molecules. Histological and biochemical changes were first evaluated in a tissue-engineered Human Reconstructed Skin (HRS) model after 11 sham or LED light treatments. LED effects were then assessed in aged/photoaged individuals in a split-face single-blinded study. Results yielded a mean percent difference between LED-treated and non-LED-treated HRS of 31% in levels of type-1 procollagen and of -18% in MMP-1. No histological changes were observed. Furthermore, profilometry quantification revealed that more than 90% of individuals showed a reduction in rhytid depth and surface roughness, and, via a blinded clinical assessment, that 87% experienced a reduction in the Fitzpatrick wrinkling severity score after 12 LED treatments. No adverse events or downtime were reported. Our study showed that LED therapy reversed collagen downregulation and MMP-1 upregulation. This could explain the improvements in skin appearance observed in LED-treated individuals. These findings suggest that LED at 660 nm is a safe and effective collagen-enhancement strategy.

Cited:

Barolet D, Roberge CJ, Auger FA, Boucher A, Germain L. Regulation of skin collagen metabolism in vitro using a pulsed 660 nm LED light source: clinical correlation with a single-blinded study. J Invest Dermatol. 2009 Dec;129(12):2751-9. doi: 10.1038/jid.2009.186. Epub 2009 Jul 9. PMID: 19587693.

The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial

Abstract


Introduction

Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model.


Methods

This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control.


Results

Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity.


Conclusions

Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects—especially in the absence of reported side effects—make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials.a

Cited:

Lang-Illievich K, Winter R, Rumpold-Seitlinger G, Schicho K, Dorn C, Klivinyi C, Bornemann-Cimenti H. The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial. Pain Ther. 2020 Dec;9(2):717-726. doi: 10.1007/s40122-020-00205-0. Epub 2020 Oct 10. PMID: 33040311; PMCID: PMC7547817.

Effect of red light and near infrared laser on the generation of reactive oxygen species in primary dermal fibroblasts

Abstract


Irradiation with red light or near-infrared (NIR) lasers can bio-modulate cellular processes or revitalize injured tissues and therefore, widely been used for therapeutic interventions. Mechanistically, this cellular or biological process, referred as Photobiomodulation (PBM), is achieved by the generation of oxide free radicals in cells and tissues. This explorative study using red light (636 nm) and Near Infra-Red (NIR, 825 nm) laser at various irradiation exposures reckons the level of oxidative stress induced by these free radicals in human primary fibroblasts. Freshly isolated dermal fibroblasts were irradiated with red light and NIR at power densities of 74 and 104 mV/cm2, respectively and, at varying fluences ranging from 5 to 25 J/cm2. Cellular oxidative stress, measured by Reactive Oxygen Species (ROS) upon quantifying fluorescently labelled oxide free radicals in cells, detected considerable variations between the irradiation exposures of red light and NIR laser. The NIR laser demonstrated high levels of ROS at all fluences, except 10 J/cm2 indicating its ability in generating of two types of oxide radicals in dermal fibroblasts, often illustrated as biphasic response. Further, the responses of these cells to variable fluences of red light and NIR laser were measured to evaluate the immediate effect of PBM on cellular activity. The production of cellular energy coincides with the amount of oxidative stress, which was two-fold higher in cells irradiated with the NIR laser, as compared with the red light. This outcome indicates that the ROS production within biological systems are more dependent on the wavelength of the laser rather than its fluences. Further studies are required to avoid ‘overdosing of PBM’ and to analyse ROS qualitatively for making the best use of the red light and NIR laser in clinics.

Cited:

Sajan George, Michael R. Hamblin, Heidi Abrahamse,

Effect of red light and near infrared laser on the generation of reactive oxygen species in primary dermal fibroblasts,

Journal of Photochemistry and Photobiology B: Biology,

Volume 188, 2018, Pages 60-68, ISSN 1011-1344, 

https://doi.org/10.1016/j.jphotobiol.2018.09.004.

Photobiomodulation in human muscle tissue: an advantage in sports performance?

Abstract


Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to vstimulate, heal, and regenerate damaged tissue. Both pre-conditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n=1045 participants). Studies used single laser probes, cluster of laser-diodes, LED-clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities.

Cited:

Ferraresi C, Huang YY, Hamblin MR. Photobiomodulation in human muscle tissue: an advantage in sports performance? J Biophotonics. 2016 Dec;9(11-12):1273-1299. doi: 10.1002/jbio.201600176. Epub 2016 Nov 22. PMID: 27874264; PMCID: PMC5167494.

Red (660 nm) and infrared (830 nm) low-level laser therapy in skeletal muscle fatigue in humans: what is better?

Abstract


In animal and clinical trials low-level laser therapy (LLLT) using red, infrared and mixed wavelengths has been shown to delay the development of skeletal muscle fatigue. However, the parameters employed in these studies do not allow a conclusion as to which wavelength range is better in delaying the development of skeletal muscle fatigue. With this perspective in mind, we compared the effects of red and infrared LLLT on skeletal muscle fatigue. A randomized double-blind placebo-controlled crossover trial was performed in ten healthy male volunteers. They were treated with active red LLLT, active infrared LLLT (660 or 830 nm, 50 mW, 17.85 W/cm(2), 100 s irradiation per point, 5 J, 1,785 J/cm(2) at each point irradiated, total 20 J irradiated per muscle) or an identical placebo LLLT at four points of the biceps brachii muscle for 3 min before exercise (voluntary isometric elbow flexion for 60 s). The mean peak force was significantly greater (p < 0.05) following red (12.14%) and infrared LLLT (14.49%) than following placebo LLLT, and the mean average force was also significantly greater (p < 0.05) following red (13.09%) and infrared LLLT (13.24%) than following placebo LLLT. There were no significant differences in mean average force or mean peak force between red and infrared LLLT. We conclude that both red than infrared LLLT are effective in delaying the development skeletal muscle fatigue and in enhancement of skeletal muscle performance. Further studies are needed to identify the specific mechanisms through which each wavelength acts.

Cited:

de Almeida P, Lopes-Martins RA, De Marchi T, Tomazoni SS, Albertini R, Corrêa JC, Rossi RP, Machado GP, da Silva DP, Bjordal JM, Leal Junior EC. Red (660 nm) and infrared (830 nm) low-level laser therapy in skeletal muscle fatigue in humans: what is better? Lasers Med Sci. 2012 Mar;27(2):453-8. doi: 10.1007/s10103-011-0957-3. Epub 2011 Jul 22. PMID: 21814736; PMCID: PMC3282894.

The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity

Abstract


The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity was investigated using a new hyperthermia treatment system, nanomist sauna (NMS). Six healthy volunteers participated and the concentration of catecholamines and cortisol, and the frequency and function of leukocytes in the peripheral blood were investigated before and after successive 7 days of hyperthermia treatment (20 min/day, 40°C, 100% relative humidity). After treatment, the blood level of adrenaline and cortisol on the 7th day was decreased compared with the 1st day, indicating the suppression of the sympathetic nervous system activity. Moreover, the frequency of CD56(+)NK, CD56(+)NKT and B cells on the 7th day tended to be increased compared with the 1st day. The frequency of HLA-DR-positive NK and NKT cells and expression of HLA-DR on B and T cells increased. The cytotoxicity of NK cells and proliferative response of B cells were also elevated. The results indicate that repetitive mild hyperthermia treatment might suppress excessive sympathetic dominance and modify immunity. Additionally, because it can provide the same effects as conventional hyperthermia treatments with minimal burden to the body, NMS may be a novel patient- and elderly-friendly hyperthermia treatment for health promotion.

Cited:

Tomiyama C, Watanabe M, Honma T, Inada A, Hayakawa T, Ryufuku M, Abo T. The effect of repetitive mild hyperthermia on body temperature, the autonomic nervous system, and innate and adaptive immunity. Biomed Res. 2015;36(2):135-42. doi: 10.2220/biomedres.36.135. PMID: 25876664.

Far Infrared Therapy Inhibits Vascular Endothelial Inflammation via the Induction of Heme Oxygenase-1

Abstract


Objective— Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR) therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation.


Methods and Results— Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-α–mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis.


Conclusions— These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients.


Far infrared (FIR) therapy improves survival of arteriovenous fistulas in hemodialysis patients, but the underlying mechanism is unknown. We now report that FIR radiation stimulates heme oxygenase-1 (HO-1) expression in endothelial cell and that the induction of HO-1 confers antiinflammatory actions that may underlie the beneficial effects of FIR therapy.

Cited:

Lin CC, Liu XM, Peyton K, Wang H, Yang WC, Lin SJ, Durante W. Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):739-45. doi: 10.1161/ATVBAHA.107.160085. Epub 2008 Jan 17. PMID: 18202320; PMCID: PMC2748062.

Far-infrared radiation acutely increases nitric oxide production by increasing Ca(2+) mobilization and Ca(2+)/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

Abstract


Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser(1179)) in a time-dependent manner (up to 40min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca(2+) levels. Treatment with KN-93, a selective inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser(1179) phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser(1179) phosphorylation. This study suggests that FIR radiation increases NO production via increasing CaMKII-mediated eNOS-Ser(1179) phosphorylation but TRPV channels may not be involved in this pathway. Our results may provide the molecular mechanism by which FIR radiation improves endothelial function.

Cited:

Park JH, Lee S, Cho DH, Park YM, Kang DH, Jo I. Far-infrared radiation acutely increases nitric oxide production by increasing Ca(2+) mobilization and Ca(2+)/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179. Biochem Biophys Res Commun. 2013 Jul 12;436(4):601-6. doi: 10.1016/j.bbrc.2013.06.003. Epub 2013 Jun 10. PMID: 23756809.

Far infrared wavelength treatment for low back pain: Evaluation of a non-invasive device

Abstract


Background: Low back pain is a significant cause of lost workplace productivity. Identification of simple, safe, and effective treatment strategies that can be used in the workplace are needed.


Objective: To assess whether far-infrared therapy (FIR) can ameliorate chronic back pain in office workers with the hypothesis that back pain could be effectively treated while at work with minimal interruption to the normal working day.


Methods: In a cohort study, 50 subjects with low back pain of at least six months duration were recruited from a Florida corporation. The subjects were instructed to use a FIR pad placed in their chairs in contact with the affected area while on the job over a 4 week period for at least 45 minutes a day during workdays. The FIR device used for the study was the Thermotex TTS Platinum Pad, a widely available FDA-registered medical device with preclinical data on its deep heating effects. The outcomes were assessed using subscales of the SF-36v2.


Results: Results showed statistically significant changes in 9 of 10 SF-36 subscales including both physical and mental components with a near significant improvement to General Health. There was progressive improvement each week in physical component and bodily pain scales. There were no reported adverse events.


Conclusions: Use of site-specific FIR therapy over a four-week period in the workplace was associated with significant clinical improvements in pain and quality of life for office workers with previously refractory low back pain.

Cited:

Ervolino F, Gazze R. Far infrared wavelength treatment for low back pain: Evaluation of a non-invasive device. Work. 2015;53(1):157-62. doi: 10.3233/WOR-152152. PMID: 26409395.

Efficacy and safety of far infrared radiation in lymphedema treatment: clinical evaluation and laboratory analysis

Abstract


Swelling is the most common symptom of extremities lymphedema. Clinical evaluation and laboratory analysis were conducted after far infrared radiation (FIR) treatment on the main four components of lymphedema: fluid, fat, protein, and hyaluronan. Far infrared radiation is a kind of hyperthermia therapy with several and additional benefits as well as promoting microcirculation flow and improving collateral lymph circumfluence. Although FIR therapy has been applied for several years on thousands of lymphedema patients, there are still few studies that have reported the biological effects of FIR on lymphatic tissue. In this research, we investigate the effects of far infrared rays on the major components of lymphatic tissue. Then, we explore the effectiveness and safety of FIR as a promising treatment modality of lymphedema. A total of 32 patients affected by lymphedema in stage II and III were treated between January 2015 and January 2016 at our department. After therapy, a significant decrease of limb circumference measurements was noted and improving of quality of life was registered. Laboratory examination showed the treatment can also decrease the deposition of fluid, fat, hyaluronan, and protein, improving the swelling condition. We believe FIR treatment could be considered as both an alternative monotherapy and a useful adjunctive to the conservative or surgical lymphedema procedures. Furthermore, the real and significant biological effects of FIR represent possible future applications in wide range of the medical field.

Cited:

Li K, Zhang Z, Liu NF, Feng SQ, Tong Y, Zhang JF, Constantinides J, Lazzeri D, Grassetti L, Nicoli F, Zhang YX. Efficacy and safety of far infrared radiation in lymphedema treatment: clinical evaluation and laboratory analysis. Lasers Med Sci. 2017 Apr;32(3):485-494. doi: 10.1007/s10103-016-2135-0. Epub 2017 Jan 26. PMID: 28127644.

The effect on serotonin and MDA levels in depressed patients with insomnia when far-infrared rays are applied to acupoints

Abstract


Little is known about the effect of far-infrared rays (FIR) on serotonin and malondialdehyde levels in depressed patients with insomnia. The purpose of this study is to assess the effect of far-infrared rays on depressed people with insomnia. A randomized design was used to determine this effect. A total of 70 inpatients were recruited with the clinical diagnosis of depression with sleep disturbance. In the experimental group, FIR was applied to three chosen acupuncture points by a patch-like sticker for a period of 15 minutes twice a week. The three acupuncture points are Nei-Kuan (PC6), Shenmen (HT7) and Sanyinjiao (SP6). The total duration of experiment was four weeks. For both experimental and control groups, serum levels of serotonin (5HT) and malondialdehyde (MDA) were examined before and after the introduction of FIR. The experimental group revealed disparate changes over different dependent variables, in which serotonin increased but MDA decreased after the introduction of FIR. These observations indicate that the serotonin pathway is involved in the pathophysiological mechanism responsible for the damaging effects of MDA on depressed patients with insomnia.

Cited:

Chang Y, Liu YP, Liu CF. The effect on serotonin and MDA levels in depressed patients with insomnia when far-infrared rays are applied to acupoints. Am J Chin Med. 2009;37(5):837-42. doi: 10.1142/S0192415X09007272. PMID: 19885944.

Effects of Pulsed Electromagnetic Field Therapy on Pain, Stiffness, Physical Function, and Quality of Life in Patients With Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Abstract


Objective: Pulsed electromagnetic field (PEMF) therapy is a potentially useful treatment for osteoarthritis (OA), but its effectiveness is still controversial. This study aimed to examine the effects of PEMF therapy and PEMF parameters on symptoms and quality of life (QOL) in patients with OA.


Methods: Cochrane Central Register of Controlled Trials, PubMed, CINAHL, EMBASE, PEDro, clinical trial registers, and reference lists were searched until April 2019. This study examined randomized, placebo-controlled trials, patients with OA, symptom and/or QOL related outcomes, and articles published in English. Two authors extracted data and completed quality assessment.


Results: Sixteen studies were included in our systematic review, while 15 studies with complete data were included in the meta-analysis. Our primary outcome was the standardized mean difference, which was equal to the treatment effect in the PEMF group minus the treatment effect in the placebo group divided by the pooled standard deviation. For pain, the standardized mean difference was 1.06 (95% CI = 0.61 to 1.51), for stiffness 0.37 (95% CI = 0.07 to 0.67), for function 0.46 (95% CI = 0.14 to 0.78), and for QOL 1.49 (95% CI = -0.06 to 3.04). PEMF parameters did not influence symptoms.


Conclusions: Compared with placebo, there was a beneficial effect of PEMF therapy on pain, stiffness, and physical function in patients with OA. Duration of treatment may not be a critical factor in pain management. Further studies are required to confirm the effects of PEMF therapy on QOL.


Impact: Our study suggests that PEMF therapy has clinically significant effects on pain in patients with OA. The current evidence was limited to the short-term effects of PEMF therapy.

Cited:

Yang X, He H, Ye W, Perry TA, He C. Effects of Pulsed Electromagnetic Field Therapy on Pain, Stiffness, Physical Function, and Quality of Life in Patients With Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Phys Ther. 2020 Jul 19;100(7):1118-1131. doi: 10.1093/ptj/pzaa054. PMID: 32251502.