The control of fire by early humans was a turning point in the technological evolution of human beings. Fire provided a source of warmth, protection from predators, a way to create more advanced hunting tools, and a method for cooking food. These cultural advances allowed human geographic dispersal, cultural innovations, and changes to diet and behavior. Additionally, creating fire allowed human activity to continue into the evening's dark and colder hours.

Claims for the earliest definitive evidence of fire control by a member of Homo range from 1.7 to 2.0 million years ago. Evidence for the “microscopic traces of wood ash” as the controlled use of fire by Homo erectus, beginning some 1,000,000 years ago, has wide scholarly support. Flint blades burned in fires roughly 300,000 years ago were found near fossils of early but not entirely modern Homo sapiens in Morocco.

The fire was used regularly and systematically by early modern humans to heat treat silcrete stone to increase its flake-ability for toolmaking approximately 164,000 years ago at the South African site of Pinnacle Point.[5] Evidence of widespread control of fire by anatomically modern humans dates to approximately 125,000 years ago.They also used fire for light.

Infrared Light from Fire

The burning of wood (or other organic materials) releases energy in the form of infrared light. When you take a photo of someone with an infrared camera, what do you see? A heat “signature” that correlates (approximately) to their metabolic activity.

What is infrared light? It is a spectrum of light that we can’t see but that powerfully shapes our biology. You sense infrared light as “heat.” The heat you feel from the sun — that’s the sensation of infrared light. The feeling of heat you get when you put your hand close to an oven, toaster, or fire — that is also infrared light. The heat of another person’s body — infrared light again. Hot springs transfer heat to your body in the form of infrared light stored in the water itself. When you take a hot shower or hot bath, the same principle is at work.

Infrared light has been used for decades as a heat source for saunas. Before IR saunas, we had sweat lodges and traditional stone saunas. In traditional saunas and sweat lodges, stones absorb energy from either an electronic heating unit (in the case of a sauna) or a fire. The light is stored in the stones and gradually released during the sweat lodge or the sauna. Both methods use light to heal the human body.

And infrared light doesn’t just transfer “heat” to your body — it turns the water in your cells into batteries. This is likely why ancient cultures recognize the importance of fire, sweat lodges, and saunas, especially in winter.

It is not a coincidence that sitting down next to a fire is so comfortable. Firelight is natural and helps to manage melatonin production as well as keeping our circadian rhythms under control.

A fireplace or fire-pit isn’t just an ornamental detail of your home, and it’s a tool you can use to live a healthier life.

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Researchers at NCI’s Center for Cancer Research have found that a technique called near-infrared immunotherapy for treating cancer has the potential to kill cancer cells in record time, essentially destroying them with the flick of a light switch. Scientists were not certain of the underlying mechanisms of this approach. Still, they succeeded in elucidating this technique in detail at the cellular and molecular level, gaining insights that could help scientists further boost the novel treatment's effectiveness. The laboratory and mouse findings, by Hisataka Kobayashi, M.D., Ph.D., Senior Investigator in the Molecular Imaging Program, and colleagues appeared November 6, 2018, in ACS Central Science.

Near-infrared immunology is an emerging technique for treating cancer that is already being studied in clinical trials. It involves identifying a protein called an antibody that recognizes and targets a specific type of cancer cell. The antibody is joined to a compound that’s sensitive to light and then administered to a patient. Within the body, the drug seeks out and attaches to only cancer cells, not healthy ones. Next, doctors apply a beam of infrared light to the cancer site, either externally or directly, using a fiber optic needle, which activates the drug and causes them to die. Research by Dr. Kobayashi and his colleagues reveals new details into how this cell death occurs.

To learn more about this phenomenon's molecular mechanisms, they studied the effects of a near-infrared immunotherapy agent called antibody-IR700 on a plate simulating human cancer cells in a petri dish using sophisticated microscopes. The researchers discovered that exposure to near-infrared light causes the immunotherapy agent to change its form from Y-shaped to globular dramatically. When it is embedded in a cancer cell's cell membrane, this warping causes scratches along the cell's protective casing. Once enough scratches occur, liquid bursts through the cell’s membrane, causing the cell to rupture in less than a minute following exposure to the light.

The researchers also studied this technique in a mouse with multiple tumors, applying different light intensity amounts to each tumor. They found that higher light intensity resulted in more cancer cells being eliminated. In mice, they detected the “leftovers” of the immunotherapy agent in the mouse’s urine just hours after near-infrared light was applied to the cancer site — a strong indication that the cancer cells were killed.

Dr. Kobayashi notes that this technique doesn’t just target cancer cells or boost the immune system to attack cancer cells — it does both. “All the cell’s proteins and even its DNA are exposed to the immune system. The immune system will recognize that [the proteins and DNA are] coming from the dying cell, and then the immune system will react only to the dying cancer cells,” he explains.

Near-infrared immunotherapy could be applied to any cancer if the right antibody is identified and used. In this study, the researchers analyzed the near-infrared immunotherapy agent IR-700, which is about to be tested in phase III clinical trials for head and neck cancer.

Although the concept of near-infrared immunotherapy is compelling, understanding why it works is critical for several reasons. Kobayashi explains, “Based on these new insights, we might be able to design a new, superior IR700 that would be improved in many respects, such as activation wavelength, stability, and cytotoxic efficacy.”

Immunological consequences after NIR

Destroying cancer cells without damaging normal cells nor compromising the host immune system is a significant benefit of NIR-PIT. Additionally, NIR-PIT induces ICD; that is, it initiates host immunity against targeted cancer cells. NIR-PIT-treated cancer cells release death signals, including calreticulin, ATP, and HMGB1, which can activate adjacent immature DCs even in tumor beds. These signals promote the maturation of immature DCs, which engulf cancer-specific antigens that are released from the ruptured tumor cell, and these mature DCs prime and educate naive T cells to become cancer-specific CD8+ T cells. Such newly primed cancer-specific CD8+ T cells proliferate and attack other cancer cells, resulting in an amplified host anti-tumor immune response. This consequential process could convert some non-immunogenic tumors into immunogenic tumors by recognizing massively released neo-antigens.

This anti-tumor immune activation occurs first in the treated tumor site. Eventually, it extends to other cancer sites because immune cells migrate throughout the body, resulting in a systemic immune response. Therefore, although NIR-PIT is a local therapy, the effect of NIR-PIT can be systemic and may affect distant metastatic sites. Indeed, some tumor-bearing mice and cancer patients achieve complete remission after a single therapy of cancer-cell-targeted NIR-PIT.

An important feature of host immune activation induced by NIR-PIT is that this therapy simultaneously activates the immune system against multiple antigens released from ruptured cancer cells. Most current targeted immunotherapies, including cancer vaccines or CAR-T therapies, identify a single target molecule to base the therapy. Having multiple clones of anti-tumor T cells, each responding to unique antigen, results in a more comprehensive response to tumors expressing a broad spectrum of cancer-specific neo-antigens.

NIR-PIT has demonstrated a profound immune response in humans. First-in-human Phase 1 and Phase 2 clinical trials of NIR-PIT with cetuximab–IR700 targeting EGFR in patients with recurrent and advanced head and neck squamous cell cancer were completed in 2016 and late 2017, respectively. Several complete remissions and multiple significant partial remissions were reported in these studies. The results far exceeded those of pre-clinical models in immune-deficient host xenograft models. Once the models were transferred to syngeneic models, a robust immune response was demonstrated. There is considerable evidence that this same response is seen in humans.

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In collaboration with the work of Jon Speer in July 19, 2020

Every industry in the world uses acronyms, and the overlap between multiple fields can be a source of confusion for professionals. There’s no room for confusion in the medical device industry, as a miscommunication could potentially lead to a product defect or adverse event with serious consequences.

Here the list:

21 CFR PART 11

Part 11 of Title 21 in the Code of Federal Regulations, commonly referred to as 21 CFR Part 11 or Part 11 for shorthand, establishes the acceptance criteria by FDA of electronic records, electronic signatures and handwritten signatures executed to electronic documents.

Compliance of quality systems with 21 CFR Part 11 requirements applies to the medical device industry, in addition to pharmaceutical, biotechnology, and other FDA-regulated industries.

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21 CFR PART 820

FDA maintains quality system regulations, or QSR, found in 21 CFR Part 820, which establishes the quality system requirements for all medical device manufacturers in the United States. Manufacturers are required to establish and maintain a quality system that is appropriate for the medical device to ensure both the safety and efficacy for its intended use, per the requirements of 21 CFR Part 820.

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483 OBSERVATION

A 483 observation, or “inspectional observation,” is a notice issued by an FDA inspector to flag potential regulatory violations found during a routine inspection. A Form 483 observation may be issued regarding any violation under FDA jurisdiction. Failure to demonstrate handling of the observed problems can be escalated to a warning letter.

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510(K) PREMARKET NOTIFICATION

A 510(k) is a regulatory premarket submission made to FDA for a Class I, II, or III medical device that doesn’t otherwise require premarket approval. The purpose of a 510(k) submission must demonstrate a safe and effective device that is substantial equivalent to an existing legally marketed device.

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APPLICATION LIFECYCLE MANAGEMENT (ALM)

Application Lifecycle Management, or ALM, involves the specification, design, development and testing of software tools. ALM systems are used to manage quality and demonstrate compliance during the software delivery process.

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AUDITING ORGANIZATION (AO)

An Auditing Organization, or AO, is responsible for auditing medical device manufacturers to evaluate conformity with quality management system requirements and other medical device regulatory requirements. An AO may be an independent organization or a Regulatory Authority (RA).

AOs participating in the Medical Device Single Audit Program (MDSAP) may conduct a single regulatory audit of a manufacturer which satisfies the relevant requirements of RAs participating in MDSAP.

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APPROVED SUPPLIER LIST (ASL)

An Approved Supplier List, or ASL, is an internal list kept by medical device manufacturers to record suppliers known to meet the quality and performance standards of the manufacturing organization.

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BILL OF MATERIALS (BOM)

A Bill of Materials, or BOM, is a complete list of raw materials, assemblies, and subassemblies required to produce a device, as well as the quantities required for each. A BOM is required to carry out change management processes for a medical device.

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COMPETENT AUTHORITY (CA)

A Competent Authority, or CA, is a body within the government of a Member State in the European Union. A CA transposes the requirements of Europe's medical device regulation (MDR) into the national law of each Member State. For example, the Federal Institute for Drugs and Medical Devices (BfArM) is the the CA for Germany.

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CONFORMITY ASSESSMENT (CA)

A Conformity Assessment, or CA, is carried out by an EU Notified Body to determine that a medical device is safe and performs as intended by the manufacturer. Medical devices must pass a conformity assessment in order to obtain CE Marking.

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COMPUTER-AIDED DESIGN (CAD)

Computer-Aided Design (CAD) software allows device manufacturers and designers to draft detailed designs, including precise specifications and measurements. CAD software files can be stored on a digital database for reference.

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CORRECTIVE AND PREVENTIVE ACTION (CAPA)

Corrective and Preventive Action, or CAPA, is a quality system process carried out by a medical device organization to reduce and/or eliminate potential sources of risk and regulatory non-conformance or noncompliance.

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CE MARKING (CE MARK)

A CE Marking, or CE Mark, certification must be obtained by medical device manufacturers for product distribution into the European Union (EU) marketplace. CE Marks are issued by third-party organizations, known as a Notified Bodies, and indicate compliance with the applicable EU medical device regulations (MDR).

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EUROPEAN COMMITTEE FOR STANDARDIZATION (CEN)

The European Committee for Standardization, or CEN, is a public standards organization that develops standards for medical devices for sale in the European Union (EU). CEN can be compared to the Food and Drug Administration (FDA), which maintains and enforces medical device regulations in the U.S. marketplace.

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CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH)

The Center for Devices and Radiological Health, or CDRH, is a branch of the U.S. Food and Drug Administration (FDA) responsible for overseeing the approval of medical devices for sale in the U.S. market and also monitors the manufacturing, performance, and safety of those medical devices.

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CLINICAL EVALUATION REPORT (CER)

A Clinical Evaluation Report, or CER, provides clinical evidence that a medical device will perform as expected, such that no safety issues occur while using it. European regulations require medical device manufacturers to perform a conformity assessment, of which include CER documentation, in order to legally market a product in the EU.

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COST OF QUALITY (COQ)

Cost of Quality, or CoQ, is a system for measuring the financial impact that a quality system and its processes has on a business. Medical device companies can use CoQ to calculate potential savings and weigh those against the costs associated with internal process improvements.

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COMPUTER SYSTEM VALIDATION (CSV)

Computer System Validation, or CSV, is a process used to demonstrate that computer systems, including hardware and software, used in medical device manufacture meet the regulations outlined in 21 CFR Part 11.

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CURRENT GOOD MANUFACTURING PRACTICES (CGMP)

Current Good Manufacturing Practices, or cGMP, are minimum standards provided by FDA for manufacturing processes and facilities. The FDA cGMP standards establish a framework for medical device manufacturers to follow and allow for greater flexibility in achieving various quality requirements.

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DOCUMENT CHANGE ORDER (DCO)

A Document Change Order, or DCO, is a formalized process in medical device change management. The DCO process involves change requests to be made within an organization to a document or system in a standardized, traceable manner.

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DE NOVO

The De Novo regulatory pathway is a classification process that uses a risk-based methodology for novel medical device to be granted market entry for sale in the U.S. For a de novo submission to be granted by FDA, general controls must indicate that the device is safe and effective for its intended use.

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DEMING CYCLE

The Deming Cycle is a methodology for monitoring quality efficacy and serves as a basis for traditional quality assurance. The Deming Cycle model is comprised of four parts: plan, do, study, and act. These parts are often summarized as PDSA.

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DESIGN CONTROLS (DC)

Design Controls or DC, as defined by FDA in 21 CFR 820.30, are a systematic process that ensures specific design requirements are met by documented procedures that control the design of the medical device. The purpose of DCs is to demonstrate that a medical device is safe, effective, and performs as expected.

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DESIGN DOSSIER (DD)

A Design Dossier, or DD, includes all contents of the technical file (TF), which describe a device’s design, manufacturing, and performance, as well as the documentation that demonstrates conformity with applicable regulatory requirements.

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DESIGN OF EXPERIMENT (DOE)

A Design of Experiment, or DoE, is a method for medical device manufacturers and engineers to validate internal processes and predict process variability in order to improve and maintain product quality.

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DESIGN FOR MANUFACTURE (DFM)

A Design for Manufacture, or DFM, is a process for optimizing the design of a medical device for manufacturing. A DFM takes into account the cost of manufacture, as well as regulatory compliance and product performance.

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DESIGN HISTORY FILE (DHF)

A Design History File, or DHF, contains all documentation related to the design and development of a medical device. Medical device manufacturers in the U.S. market are required by law under FDA 21 CFR Part 820 to maintain a DHF.

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DEVICE HISTORY RECORD (DHR)

The Device History Record, or DHR, acts as a record of production for a medical device and demonstrates it was manufactured according to information stored in the device master record (DMR). Manufacturers operating in the U.S. are required under CFR Part 820.184 to maintain a DHR, which contains information such as acceptance records for units or batches of products, unique product identifiers, and product counts.

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DEVICE MASTER RECORD (DMR)

A Device Master Record, or DMR, is a record of all the information and specifications required to produce a medical device. The DMR contains instructions for manufacturing, drawings and specifications for devices, and requirements for labeling and packaging. Manufacturers are required by FDA to maintain a DMR under CFR Part 820.181.

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DOCUMENT MANAGEMENT SYSTEM (DMS)

A Document Management System, or DMS, is a tool used to store and manage documents related to medical device development, as well as track any changes made to documents throughout the product lifecycle on an ongoing basis. A DMS is not synonymous with a Quality Management System, or QMS, which stores documents but also has a regulatory compliance focus.

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ENGINEERING CHANGE ORDER (ECO)

An Engineering Change Order, or ECO, is a process that is triggered when an issue is raised with a medical device in terms of performance, cost-effectiveness, or the process of manufacturing the device. An ECO is typically followed by an analysis to determine whether action should be taken. Depending on the nature of the change, an ECO may lead to a CAPA investigation.

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ESTABLISHMENT INSPECTION REPORT (EIR)

An Establishment Inspection Report, or EIR, is made by FDA in the event a Form 483 is issued following an inspection. The next steps after receiving an official EIR from FDA will be determined by the severity of the issues observed, as well as the 483 response. If significant deficiencies are observed, FDA may decide to issue a warning letter.

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ENTERPRISE RESOURCE PLANNING (ERP)

Enterprise Resource Planning, or ERP, refers to the management of business processes within the organization of a medical device organization. This is often carried out with the use of ERP tools that gather and organize business data and automate processes related to human resources and business practices.

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IN VITRO DIAGNOSTIC REGULATION (IVDR)

The European Commission's new IVDR 2017/746, which is shorthand for In Vitro Diagnostic Regulation, is Europe's new regulation for in vitro diagnostic devices that is scheduled to go into effect 26 May 2022. The IVDR requires all existing IVD devices being sold in the EU market to undergo recertification for compliance with the new requirements, which supersede the previously held directives for in-vitro diagnostic devices (IVDD).

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EU MEDICAL DEVICE DIRECTIVE (MDD)

MDD is the Medical Device Directive for medical devices sold in the European marketplace, which was replaced in 2017 by the medical device regulation (MDR. The purpose of the directive was to harmonize laws and standards around medical devices marketed in the European Union.

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EU MEDICAL DEVICE REGULATION (EU MDR)

EU MDR is a common abbreviation for the medical device Regulation (EU) 2017/745, which mandates the quality and safety requirements for medical devices produced and marketed in the European Union (EU). The EU medical device regulation supersedes the previously held medical device directives (MDD) that were in place up until 2017 and places strong emphasis on a total product lifecycle approach.

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EUROPEAN DATABASE ON MEDICAL DEVICES (EUDAMED)

The European Database on Medical Devices, or EUDAMED, is a database developed by the European Commission to facilitate compliance with European medical device regulations. It's intended to function as a multipurpose system for registration, collaboration, and communication for multiple stakeholders in the medical device industry.

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FOOD AND DRUG ADMINISTRATION (FDA)

The Food and Drug Administration, or FDA, is a federal agency of the U.S. Department of Health and Human Services. The FDA is responsible for approving medical devices for manufacture and distribution within the U.S. Medical device manufacturers operating within the U.S. market are subject to FDA inspections and compliance with the requirements outlined in Title 21 of the Code of Regulations.

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FAILURE MODES AND EFFECTS ANALYSIS (FMEA)

Failure Modes and Effects Analysis, or FMEA, is a method used to identify failures in a design or process associated with a medical device. FMEA is distinct from ISO 14971, the international standard for medical device risk management. The FMEA method can be broken into two parts: PFMEA for processes, and DFMEA for designs.

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FAULT TREE ANALYSIS (FTA)

Fault Tree Analysis, or FTA, is an analytical method aimed at identifying points of failure and risk within a quality system. In medical device manufacture, FTA can be applied throughout the course of risk management activities to identify possible sources of risk.

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FREEDOM TO OPERATE (FTO)

Freedom to Operate, or FTO, refers to product infringement on intellectual property. Device manufacturers typically declare whether they have FTO in each market in which they plan to sell a new product.

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GENERAL SAFETY AND PERFORMANCE REQUIREMENTS (GSPR)

Medical device manufacturers are required to comply with the General Safety and Performance Requirements (GSPRs) of the new EU MDR. The regulation splits GSPRs into three chapters, general requirements, requirements regarding design and manufacture, and requirements regarding the information supplied with the device.

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HAZARD IDENTIFICATION (HID)

Hazard Identification, or HID, is a risk management process in which device manufacturers determine whether situations, processes, or items associated with the production of their device may have the potential to cause harm.

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INVESTIGATIONAL DEVICE EXEMPTION (IDE)

An Investigational Device Exemption, or IDE, is an FDA exemption that allows an investigational device to be used for testing a device against premarket approval standards. An investigational device can be used to gather data on the safety and effectiveness of the device, and this data is submitted as an IDE for review by FDA.

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IEC 60601

IEC 60601 is a standard pertaining to electrical medical equipment. Any medical device containing electronics must pass the necessary requirements outlined in IEC 60601.

Programmable Electrical Medical Systems, or PEMS, is a key part of what's covered in IEC 60601. PEMS consists of software, firmware, and equipment that can be programmed to carry out functions that aid medical care or treatment. The standard also covers mechanical safety, labeling, and risk management.

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IEC 62304

IEC 62304 is a software framework that outlines software engineering and documentation practices. It is also recognized by FDA and provides a risk-based framework that can be used throughout entire medical device software lifecycle.

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INSTRUCTIONS FOR USE (IFU)

Instructions for Use, or IFU, are instructional materials used to convey relevant information to the end user. These materials must take into account the capabilities and limitations of the end user in order to communicate instructions as concisely and objectively as possible.

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INTERNATIONAL MEDICAL DEVICE REGULATORS FORUM (IMDRF)

The International Medical Device Regulators Forum, or IMDRF, is a voluntary working group of international medical device experts whose purpose is to harmonize medical device standards and regulations. The IMDRF supersedes the Global Harmonization Task Force.

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INSTALLATION QUALIFICATION (IQ), OPERATIONAL QUALIFICATION (OQ), AND PERFORMANCE QUALIFICATION (PQ)

Installation Qualification, Operational Qualification, and Performance Qualification are terms that pertain to medical device software and equipment validation. IQ relates to the proper installment of software or equipment, OQ concerns meeting the necessary regulatory requirements, and PQ has to do with compliance of the software or equipment performance.

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INSTITUTIONAL REVIEW BOARD (IRB)

An Institutional Review Board, or IRB, is a body that oversees human medical research in the U.S. and ensures that the human rights of all subjects are protected. An IRB has the authority to approve or disapprove research or to request modifications to research practices.

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INTERNATIONAL ORGANIZATION FOR STANDARDIZATION (ISO)

The International Organization for Standardization, or ISO, is a non-governmental organization of experts providing voluntary international standards, based on the subject matter expertise of members, to enable and promote innovative solutions to worldwide challenges.

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ISO 13485:2016

ISO 13485:2016 is the internationally harmonized standard for medical device quality management systems (QMS). To align with ISO 13485:2016, QMS contents should address the specific, applicable requirements outlined in the standard, in addition to the applicable regulatory requirements according to the markets where the medical device will be manufactured and marketed.

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ISO 14971:2019

ISO 14971:2019 is the latest version of the international standard for medical device risk management. The globally recognized standard offers best practices for using a proactive approach to risk management throughout the entire lifecycle of a medical device.

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ISO 9001

ISO 9001 is an international standard that specifies the requirements for a quality management system. Belonging under the umbrella of the ISO 9000 standard, 9001 is the only one that offers a certification pathway for manufacturers. This standard assumes a specialized focus on ensuring users receive good-quality products and services.

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IN VITRO DIAGNOSTIC (IVD) DEVICES

IVD refers to In Vitro Diagnostic devices. As defined in IVDR (EU) 2017/746, IVD can describe devices or equipment “intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body.”

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MANUFACTURER AND USER FACILITY DEVICE EXPERIENCE (MAUDE)

Manufacturer and User Facility Device Experience, or MAUDE, is a database for medical device electronic reporting (eMDR) submitted to the FDA by manufacturers, importers, device user facilities, health care professionals, patients, and consumers.

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MEDICAL DEVICE REPORTING (MDR)

Medical Device Reporting, or MDR, refers to a surveillance tool maintained by FDA that is used to monitor the performance and safety of medical devices after being placed on the market. MDR provides voluntary reporting capabilities to both medical device manufacturers and consumers for public-use.

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MEDICAL DEVICE SINGLE AUDIT PROGRAM (MDSAP)

The Medical Device Single Audit Program, or MDSAP, is a program allowing medical device manufacturers to gain access into multiple global markets through one audit event. There are currently five active participating regions of MDSAP, including Australia, Brazil, Canada, Japan, and the United States.

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MEDICAL DEVICE USER FEE AMENDMENTS (MDUFA)

Medical Device User Fee Amendments, or MDUFA, refers to changes made to the fee structure in which medical device companies are expected to pay to FDA in order to register their establishments and devices. These fees also apply to application or notification submissions made to the FDA.

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MEDICAL DEVICE QUALITY MANAGEMENT SYSTEM (MDQMS)

A Medical Device Quality Management System, or MDQMS, is a quality management system built from the ground up for the medical device industry. Unlike a legacy QMS or ad hoc system, a MDQMS typically includes templates and workflows that align with medical device industry requirements and best practices.

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MANUFACTURING RESOURCE PLANNING (MRP)

Manufacturing Resource Planning, or MRP, is a way of compiling, organizing, and planning various activities carried out by a medical device manufacturer (or with any business). The method involves simulating hypothetical scenarios to ensure resources are being used effectively. This term has fallen out of use in recent years and may also be referred to as ERP.

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NOTIFIED BODY (NB)

A Notified Body, or NB, is a third-party auditing organization that assesses the quality and conformity of medical device products seeking market entry into the European Union.

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NONCONFORMANCE REPORT (NCR)

A Nonconformance Report, or NCR, is used to document non-conforming material observed during quality control activities or inspection. A NCR details the identified issue(s) of nonconformance, the severity and impact of the non-conformance, how it occurred, and how nonconformance will be managed to prevent recurrence.

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NONSIGNIFICANT RISK (NSR)

Nonsignificant Risk, or NSR, is a measure of risk as outlined by ISO 14971. Determining whether a risk is significant or nonsignificant involves assessing the probability of direct harm, probability of harm from not using the device, and probability of harm from misinformation.

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OWN BRAND LABELING (OBL)

Own Brand Labeling, or OBL, occurs when a manufacturer sells a medical device in the EU that already has a CE Marking and does so under its own brand.

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ORIGINAL EQUIPMENT MANUFACTURER (OEM)

An Original Equipment Manufacturer, or OEM, is an organization that produces goods which are used as subparts in products of a third-party company, which then sells the end products to consumers.

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PERSONS RESPONSIBLE FOR REGULATORY COMPLIANCE (PRRC)

The European Commission requires manufacturers to designate at least one person with the requisite expertise in the field of medical devices from within their organization as the Person Responsible for Regulatory Compliance (PRRC).

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PRODUCT DEVELOPMENT (PD)

Product Development, or PD, is the pre-market process of building a medical device. In the medical device industry, this process encompasses the design and development of a product.

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PRODUCT DATA MANAGEMENT (PDM)

Product Data Management, or PDM, is the handling of data as it relates to a medical device within a software system. Modern medical device companies often use PDM tools to compile product data and automate management protocols.

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PRODUCT LIFECYCLE MANAGEMENT (PLM)

In the manufacturing sector, Product Lifecycle Management, or PLM, is a system for managing and overseeing the development and distribution of a product. This process applies to the inception, design, regulatory approval, manufacturing, marketing, and post-market phases of medical devices until the product is no longer on the market.

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PREMARKET APPROVAL (PMA)

Premarket Approval, or PMA, is the regulatory pathway to market required for Class III devices under FDA regulations. The PMA submission process typically involves clinical trials with human participants, as well as laboratory testing, to demonstrate the safety and efficacy of the device.

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POST-MARKET SURVEILLANCE (PMS)

Post-Market Surveillance, or PMS, is the process of monitoring a medical device after it has gained market entry for sale and distribution of use for use by patients within the marketplace. PMS involves gathering data and feedback on the performance of a device on the market, and it is a mandatory process for compliance with most regulations and standards, including 21 CFR Part 820, EU MDR, and ISO 13485:2016.

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PROOF OF PRINCIPLE (POP)

Proof of Principle, or POP and also known as Proof of Concept, is the demonstration that the initial concept behind a medical device is feasible. The POP typically includes criteria for success that must be met in order to proceed with product development.

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PRODUCTION PLANNING AND CONTROL (PPC)

Production Planning and Control, or PPC, is a process used to organize the production, including design and development activities, and the manufacture of a medical device. A PPC process is usually comprised of inputs, outputs, and control systems. Regulations for design and development planning are found under FDA CFR 21 Part 820.30.

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QUALITY ASSURANCE (QA)

Quality Assurance, or QA, is a method used to prevent defective, nonconforming products. QA professionals engage in activities intended to improve the product development and testing processes, as well as maintaining compliant marketing and distribution processes.

A quality management system can be considered as a QA tool itself, as it serves as a single source of truth for all quality policies and procedures for the final product.

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QUALITY CONTROL (QC)

While QA focuses on the process, Quality Control, or QC, focuses on the product. QC is system for identifying defects in a medical device during the post-production phase, prior to product distribution. The goal of quality control is to ensure the product conforms to specified requirements and will meet expected performance criteria upon end user interface. QC and QA are complementary aspects of a QMS.

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QUALITY MANAGEMENT SYSTEM (QMS)

A Quality Management System, or QMS, is an organizational tool for implementing and maintaining activities, documents, and tasks as it relates to responsibilities, procedures, processes, and resources. A QMS is instrumental in achieving regulatory compliance and in producing safe and effective medical devices. At minimum, a quality system should include design controls, risk management, document control and records management, and supplier management.

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QUALITY SYSTEM INSPECTION TECHNIQUE (QSIT)

The Quality System Inspection Technique, also known as the QSIT method, is a type of FDA inspection that uses a top-down approach to reviewing the four main subsystems within a company's QMS. The top-down approach used by the FDA inspector begins with reviewing the company's procedures before drilling down into the quality records for those processes. The quality records serve as proof the company is following its written procedures.

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QUALITY SYSTEM RECORD (QSR)

A Quality System Record, or QSR, is a record that acts as a source file for all documentation, procedures, and records that are located within a QMS. Medical device companies can use their QSR as a reference to navigate other aspects of their QMS. QSR can also refer to Quality System Regulation, shown below.

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QUALITY SYSTEM REGULATION (QSR)

The Quality System Regulation, or QSR, for medical devices in the U.S. is outlined in FDA 21 CFR Part 820. The QSR requirements are based on methods for facilities, and controls used for, carrying out all phases of processes throughout the lifecycle of a medical device. These aspects include design, manufacture, packaging, labeling, storing, installing, and servicing of medical devices intended for use by humans.

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REGULATORY AFFAIRS (RA)

Regulatory Affairs, or RA, professionals in the medical device industry play a strategic role throughout the product lifecycle, such as ownership of a company's go-to-market strategy for satisfying legal requirements of product commercialization, regulatory submission protocol, and postmarket surveillance methods. The RA role serves a critical function for effectively communicating and executing appropriate regulatory strategies to ensure compliance.

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RISK ANALYSIS (RA)

Risk Analysis, or RA, is a method used in risk management to identify specific risks associated with a design, procedure, or process used in the manufacture of a medical device. The RA process will include identifying the medical device, the persons involved, the scope of the risk analysis, and relevant date(s). Preliminary hazard analysis, FMEA, and fault tree analysis are all methods used to carry out risk analysis for a medical device.

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RISK MANAGEMENT (RM)

Risk Management, or RM, is a process used by medical device companies to identify, control, and prevent hazards and risks/sources of harm that might arise during the use of a medical device. The internationally recognized standard for medical device RM processes are outlined in ISO 14971:2019.

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RESEARCH USE ONLY (RUO)

Research Use Only, or RUO, is a term used to indicate that a medical device product or instrument does not have an intended medical purpose and instead is to be used for research purposes only. Devices used for research in IVD product development are often labeled RUO.

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SOFTWARE AS A MEDICAL DEVICE (SAMD)

Software as a Medical Device, or SaMD, is a class of software used for medical functions, without needing a hardware component to serve that function. An application or software that's used to diagnose, cure, prevent, or mitigate disease are all considered to be classes of SaMD.

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SUPPLIER CORRECTIVE ACTION REQUEST (SCAR)

A Supplier Corrective Action Request, or SCAR, is a formal notice sent to a supplier by a medical device company upon the observance of issues related to nonconforming products or materials. Such issues impact the quality of the provided goods, and the purpose of the SCAR is to solicit action from the supplier to identify and correct the issue(s) raised.

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SUBSTANTIAL EQUIVALENCE (SE)

Substantial Equivalence, or SE, is a regulatory requirement by FDA for market clearance of new products through a 510(k) premarket submission. To declare substantial equivalence, a company must prove their device is as safe and effective as a similar predicate device. SE is required for regulatory submissions for which a premarket approval (PMA) is not required.

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SAFE MEDICAL DEVICES ACT (SMDA)

The Safe Medical Devices Act, or SMDA, is a law which passed in 1990 establishing HHS as the governing authority over device user facilities to report incidents in which a medical device may have caused or contributed to the serious injury, illness, or death of a patient.

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STANDARD OPERATING PROCEDURE (SOP)

A Standard Operating Procedure, or SOP, is an internal procedure created by an organization to standardize a routine process for ease of repeatable. A SOP is typically a written document comprised of a series of prescriptive instructions to be followed by individuals and teams. Medical device companies are required to create and maintain SOPs for routine processes as part of their QMS.

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STATISTICAL PROCESS CONTROL (SPC)

Statistical Process Control, or SPC, is a method used to control a process through the use of statistical techniques. This involves compiling data from a process and building cause and effect models to predict and account for various outcomes.

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SIGNIFICANT RISK (SR)

Significant Risk, or SR, is a measure of risk as defined by ISO 14971. Any device that poses a serious risk to the health or safety of a human subject is categorized as SR.

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SINGLE-USE DEVICES (SUDS)

Single-Use Devices, or SUDs, are disposable devices intended to be used for a singular event or procedure for one patient only. These devices are to be disposed after use rather than sanitized and re-used.

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SUMMARY TECHNICAL DOCUMENTATION (STED)

Summary Technical Documentation, or STED, is format manufacturers can use to record required information about how a medical device was designed, developed, and manufactured for submission to a Regulatory Authority or Notified Body to demonstrate conformity. The STED format represents the documentation required for Technical Files.

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TECHNICAL FILE (TF)

A Technical File, or Design Dossier  for Class III devices, includes specific details about a medical device's design, composition, intended use, function, and clinical evaluation. TF are a key requirement of obtaining CE marking for a device.

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UNIQUE DEVICE IDENTIFICATION (UDI)

Unique Device Identification, or UDI, is a system established by the FDA to catalog and identify each individual device for sale in the U.S. market by assigning a custom identifier that can be read by both humans and machines. A UDI is distinct from a Universal Product Code (UPC), as the UDI is used to identify a medical device on the FDA website via the AccessGUDID portal.

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UNIVERSAL PRODUCT CODE (UPC)

A Universal Product Code, or UPC, is a code printed on retail packaging consisting of a barcode and a 12-digit number. The code can be used to track inventory for retailers and is considered to be an alternative tracking method to UDI, the official identification system used by FDA.

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VERIFICATION AND VALIDATION (V&V)

Verification and Validation, also known as V&V, are activities for testing and confirming whether a medical device meets the design procedures and is ready to be released for manufacture. Design verification ensures you designed the device correctly and design validation ensures you designed the correct device. These processes tend to involve careful tests, trials, and analyses.

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VOLUNTARY ACTION INDICATED (VAI)

Voluntary Action Indicated, or VAI, is a term used by the FDA in establishment inspection reports (EIR) to indicate regulatory action is not required, following the observance of objectionable conditions or practices during an inspection. On the contrary, Official Action Indicated (OAI) would indicate regulatory or administrative action is required by FDA to correct an issue found during an inspection.

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WARNING LETTER (WL)

A Warning Letter (WL) is an official notice made by FDA in response to regulatory violations that have been escalated from a 483 observation. Violations may include anything from wrongful claims about the device to missing design controls. A WL will provide a detailed explanation of the violation and what is required of companies for a corrective action plan.

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WORK IN PROGRESS (WIP)

Work in Progress, or WIP, is a term used to refer to partially finished goods in manufacturing or within a design history record (DHR). Inventory that has entered the manufacturing process and can no longer be classed as raw materials but is not yet a finished product is classed as WIP.

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The information provided in this article is for educational purposes only and is not intended to support the safety or effectiveness of any medical device, or diagnose, treat, cure, audit, procedure, quality standard or prevent any disease.

As humans, we are made of energy and fueled by light. While nutrition and exercise play a role in our well-being and health, light plays a crucial role in us functioning optimally. New and groundbreaking research is unearthing a new understanding of how our cells function and the evidence points to the power of light.

Through technological advancements in science, it’s discovered that our bodies operate similar to a battery. Wavelengths of light give us power, while our overall health determines our ability to receive and maintain the energy from light. And this is where light therapy comes into the equation.

What is Red Light Therapy

Science has proven that our bodies interact with specific wavelengths that benefit our bodies in various ways. 

Red light therapy devices, such as light therapy masks, shine red and near-infrared light onto the skin, stimulating the production of adenosine triphosphate (ATP) within the mitochondria. By stimulating ATP, damaged cells heal, and new cells are produced faster than normal. But we’ll talk more about that in-depth a little later.

Red light therapy comprises both red light and infrared wavelengths, penetrating through the skin’s layers, right into the cells. Red light wavelengths boost collagen and elastin and improve cell communication. It penetrates superficially and helps aid various skin conditions. 

Near-infrared wavelengths stimulate healing, increase mitochondrial function, and improve blood flow and tissue oxygenation. Near-infrared wavelengths penetrate deeply into the body. 

Recharging Your Body From Within

At the core of your body’s healing capabilities are the mitochondria. The mitochondria play a vital role in your internal organs and tissue, including the liver, skin, heart, and muscles. It’s in charge of the body’s energy supply via ATP (adenosine triphosphate).

With both working together, they provide energy to our body and maintain the cell cycle and growth. This is why you’ll often hear the mitochondria referred to as the “powerhouse of the cell.”

Here's how the mitochondria is affected by red light:

1. LED light wavelengths from 600-800nm(red) and between 810-850nm(infrared) penetrate through the skin into the cells via a red light therapy device.
2. Light enters the cell's mitochondria, absorbed by chromophores which include EZ water and protein cytochrome c oxidase (CCO), resulting in stimulating activity.
3. Subsequently, three molecules are affected: Adenosine Triphosphate (ATP), Reactive Oxygen Species (ROS), and Nitric Oxide (NO).

Interestingly, our body weight is made of 70% water, with 99% of our bodies' molecules also made of water, making it a powerful component in red light therapy treatment.

Research by Prof Gerald Pollock of the University of Washington proved that water adjacent to a cell is structured water, also known as EZ water. This specific water forms a separation of charge, functioning in the body as positive and negative poles - similar to a battery.

What Does “Red Light Therapy” Mean?

While we’ve been talking about red light therapy, what does it actually mean? Typically, “red light therapy” refers to natural light treatments which deliver red and near-infrared wavelengths as natural sunlight using LEDs or cold lasers. 

While you may think red light therapy includes all colors of light, it doesn’t. The term doesn’t include blue or white light, and it isn’t equivalent to full-spectrum light. Red light therapy doesn’t rely on heat, differentiating it from other light-based treatments such as infrared saunas and heat therapy. 

Red light therapy is also known as RLT, photobiomodulation (PBM), phototherapy, LED therapy, LED light therapy, infrared therapy, low-level laser therapy, or low-level light therapy (LLLT). 

Red Light Therapy: The Multilevel Treatment

As stated before, red light therapy works to heal the entire body and functions on multiple levels.

Molecular

• Adenosine triphosphate (ATP)
• Retrograde mitochondrial signaling
• Reactive oxygen species
• Water, opsins, chromophores, cytochrome c oxidase
  

Calcium

• Melatonin
• Gene transcription factors
• Heat-shock proteins
• Akt/mTOR/CyclinD1 pathway
• Brain-derived neurotrophic factor
  

Cellular

• Inflammation, Cytoprotection, Proliferation
• Protein synthesis
• Stem cell production and migration
• Immune cell viability
• Retrograde mitochondrial signaling
• Transforming growth factor
• Pro-and anti-inflammatory cytokines
• Vascular endothelial
• Mitochondrial membrane potential

Tissue

• Muscles: Increase endurance, tone density
• Brain: Improves cognition and immune
• Nerves: Repair and pain relief
• Healing bones, tendons, and wounds
• Increases hair growth
• Improvement of the collagen network, anti-aging, skin disorders
• Fat re-absorption improved by enhanced micro-circulation
• Improved immunity and lymphatic system

Systemic Effects: Positive Affects on Bodily Systems

Red light therapy affects the body in multiple ways, including bodily systems:

Fascia

Fascia is the thin casing of connective tissue that surrounds virtually every organ, muscle, nerve fiber, blood vessel, and bone in place. While it performs as an internal structure for your body, the fascia also contains nerves, making it almost as sensitive as skin.

The fascia may look like a layer of tissue; however, it’s made up of interwoven layers of collagen and elastin fibers. The fascia is overlooked, yet over recent years, it has been the key to understanding how changes in one area of our body affect others. Red light therapy works to improve communication within the fascia network.

Gut-Brain Axis

The gut-brain axis connects the emotional and cognitive centers of the brain with peripheral intestinal functions. Recent research discovered the importance of gut microbiota concerning these interactions.

Red light therapy can positively influence mood and neuropsychological issues by the following:

• Reducing gut spasms and bowel inflammation.
• Increasing neurotransmitters, activating the brain’s immune system, thus increasing blood flow and eliminating toxins.
• Reduce blood pressure and increase circulation to eliminate brain fog and anxiety.
• Changes the vagus nerve, which connects the gut and brain. It plays a role in stress and social communication.
• Changes of the micro-biome.

Immune System

Red and near-infrared light penetrate through the skin into the cells, which results in low-dose metabolic stress that strengthens the cells’ anti-inflammatory and natural defense systems. In turn, the body becomes resilient to infections.

Safe and low exposure to red light therapy improves the body’s response to external viruses and bacteria. Red light therapy can influence the immune response in the following ways:

• Enhances proliferation, maturation, and motility of fibroblasts.
• Activates macrophages to behave as phagocytes.
• Increases production of fibroblast growth.
• Proliferation and activation of lymphocytes.
• Release of pro-inflammatory cytokines and mast cell degranulation.
• Activation of mast cells results in reduced inflammation.

Circulatory System

Red light therapy is scientifically proven to increase the micro-circulation of blood and support the circulatory system as a whole by stimulating the development of new capillaries which carry oxygen throughout the body.

Proper oxygen supply and flow are essential for the proliferation of cells, protein synthesis, tissue restoration, inflammatory response, and angiogenesis. In addition, circulation is also responsible for waste elimination, specifically degenerated cells.

Nervous System

The nervous system includes the brain, spinal cord, neurons, and neural support cells, which is your body’s command center. It controls your movements, automatic responses, and other body systems such as digestion and breathing.

Red light therapy affects the nervous system in the following ways:

• Releases growth factors.
• Increases the vascular network and collagen.
• Facilitates neural regeneration.
• Regenerates the nerve lesions and damaged nerves at a faster rate.
• Improves the electrophysiological function.
• Myelination of fibers.

For all forms of nerve damage, red light therapy offers non-pharmaceutical treatment options. 

Stem Cells

Red light therapy shows impressive results regarding stem cell growth, maximizing the potential of stem cell implantation for various medical needs. Therefore, red light therapy may show positive results after surgery to stimulate stem cells which repair tissues and organs.

In studies, red light therapy has proven to stimulate mesenchymal stem cells in bone marrow, enhancing their ability to reach the brain. This research shows the possibilities of using red light therapy to heal degenerative conditions, including Alzheimer’s, Parkinson’s disease, and dementia.

The Origins of Modern Red Light Therapy

It’s clear red light therapy provides multilevel treatment to the body, becoming a popular natural and holistic option for both professionals and consumers, but where did it come from? 

Light therapy technology isn’t new; it’s been around for decades as NASA experimented with red light therapy during the 1980s and 1990s. Over the past 10-20 years, red light therapy reached a breakthrough in LED lighting technology, allowing the production of safe and affordable clinical and at-home devices.

In 2016, Kaiyan Medical became the first leading manufacturer of red light therapy of affordable FDA-approved and MDASAP-approved light therapy devices.

What is Holistic Medicine?

We mentioned red light therapy being a holistic treatment option, but what does that mean. Holistic medicine is a full-body approach to healthcare. By focusing on the body, mind, and soul, the body receives the full support and care it needs to function optimally.

Principles of Holistic Medicine

Holistic medicine is based on the following principles:

• Optimal health is the combination of emotional, mental, spiritual, social and physical wellness.
• The focus is to prevent first, and treat second.
• The disease or illness is not caused by a single area, rather the whole body.

The purpose of treatment is to identify the underlying cause of the disease, rather than treating only the symptoms.

6 Main Benefits from Red Light Therapy

While there are endless benefits the body receives from red light therapy, here are the six main benefits.

Relieves Pain And Discomfort

Photobiomodulation, in other words, red light therapy, has proven effective against carpal tunnel syndrome, mucositis, neck pain, menstrual cramps, temporomandibular joint pain, and neuropathic pain from amputation. It also significantly reduces the pain of hypersensitivity while improving sensorimotor function.

These improvements come after anti-inflammatory cells populate the injured area, providing long-lasting pain relief. In addition, it’s also been shown to provide effective relief by affecting the following:

• Represses cyclooxygenase and prostaglandins.
• Activating peripheral opioid receptors.
• Increasing endorphins serotonin release.
• Stimulates the metabolism.
• Changes nerve transmission.

Repairs Skin

Red light therapy has proven to be highly effective in rapidly treating wounds from burns, scars, bedsores, ulcers, surgery incisions, and diabetic neuropathy.

NASA strongly supports this claim as this technology was used in treating wounds. Red and near-infrared light proves effective in all four phases of the wound-healing process:

• Coagulation
• Inflammation
• Migration
• Remodeling
  

These processes are regulated by various factors connected via nitric oxide (NO) signaling release, adjusted by light energy. 

An issue the body encounters when trying to heal a wound is low oxygen flow, and red light increases the flow of oxygen, speeding up the natural healing process. By reducing inflammation and increasing oxygenation of the wounded area, blood vessels can form, rapidly repairing the area, lessening pain and scarring. 

By reducing pain, red light therapy eliminates the reliant on pharmaceutical painkillers during the healing process.

Revives Immunity

The human body receives energy on the cellular level, maintaining communication between organs and ensuring disease resistance.

A strong immune system works to protect the body from harmful bacteria and viruses at all times. With red light therapy, the body receives a boost of support as it releases nitric oxide and melatonin, two components involved in DNA repair and antimicrobial.

This process is called hormesis. Red and near-infrared wavelengths penetrate through the skin into the cells, causing mild metabolic stress, which stimulates cells to activate their anti-inflammatory and antioxidant response.

With the support of red light therapy, the body is better prepared to fight infections. Numerous studies have proven red light therapy to have the following effects on the immune system:

• Improves melatonin production
• Increases NO levels
• Improves antioxidant production
• Improves thyroid function
• Stimulates T cells pre-operatively
• Increases flow of neurotransmitters
• Boosts collagen and elastin production
• Encourages lymph node activity
• Enables the transportation of immune cells
• Stimulates optimal function of cells and organelles

Reduces Inflammation

Inflammation in the body can be acute and topical (short-term, resulting from sprains, infections, and accidents) or chronic and general (long-term, caused by ongoing conditions).

Acute inflammation is a healthy bodily response; however, chronic and general inflammation can negatively impact long-term health.

As of today, the current treatment for inflammation is NSAID or steroid drugs, both having a detrimental effect on the healing process and long-term health. Red light therapy stimulates the body to activate its natural healing mechanism, reducing the health risks of long-term drug use.

Red light therapy decreases the number of inflammatory cells, increases fibroblast proliferation (cells that synthesize collagen and other matrix macromolecules), stimulates angiogenesis (creation of new blood vessels), and activates the body’s anti-inflammatory, antioxidant response.

The following conditions are connected with chronic and acute inflammation, all proving promising results with red light therapy treatment:

• Arthritis
• Asthma
• Sinusitis
• Muscular sprains
• Fibro-myalgia
• Neuron inflammatory disorders such as Alzheimer’s
• Irritable bowel syndrome and colitis
• Rheumatic conditions

Regains Performance

Red light therapy is extremely popular in competitive sports and performance. It offers natural and non-pharmaceutical treatment, which applies to many areas of the body.

Aside from the overwhelming benefits on overall health, red light therapy encourages muscles growth and repair by stimulating the production of ATP, which aids in faster recovery and better performance.

Red light therapy used before training prepares and strengthens the body while aiding muscle recovery after training.

Here are the scientifically documented effects of red light therapy:

• Reducing DOMS (Delayed Onset Muscle Soreness)
• Enhanced endurance and performance
• Increasing sleep quality
• Improving sexual function and libido (including Testosterone)
• Aiding weight loss
• Boosting cognitive function
• Reversing skin aging
• Reducing cellulite ‍

Reduces symptoms of depression and seasonal affective disorder

Seasonal affective disorder (SAD) is a form of depressions, impacting 5% of Americans, specifically during the winter when there’s less natural sunlight. SAD is also known as seasonal depression or winter blues.

Many people treat SAD symptoms via bright white light treatment, mimicking the sun’s light daily. However, researchers recommend natural light treatment, like red light therapy, to help with light deficiency. Over recent years, physicians recommend red light therapy alongside psychotherapy and medication.

Who Can Use Red Light Therapy?

While many people are using red light therapy devices for at-home treatment, red light therapy systems are found in many clinical and professional settings:

Skincare Professionals: Red light therapy is a popular skincare treatment among Hollywood celebrities, including Kourtney Kardashian, Julia Roberts, and Emma Stone. Leading skincare professionals like dermatologists and aestheticians use red light therapy to help promote collagen production, reduce wrinkles, and treat skin conditions.

Health Practitioners: Health practitioners from all specialties are incorporating red light therapy into their practice. Dentists use it to reduce inflammation, physicians for mental health conditions, and oncologists for cancer side effects.

Natural Health Experts: Leading voices in the health and wellness industry such as Dr. Sarah Ballantyne, Ben Greenfield, and Dave Asprey strongly support the use of red light therapy. Paleo and Keto health experts like Robb Wolf, Mark Sisson, Luke Story, and Dr. Anthony Gustin also support red light therapy.

Sports Medicine Pros: The National Sports Association of Sports Medicine (NASM) adopted red light therapy to treat sports injuries. Top trainers and doctors, including Dr. Troy Van Biezen and Dr. Ara Suppiah, use red light therapy to heal their athletes.

Elite Pro Athletes: Professional athletes worldwide, including NFL stars like Patrick Peterson, UFC champion Anthony Pettis, and gold medal gymnast Sanne Weavers use red light therapy to enhance performance and quicken recovery.

Fitness & Training: World-renown fitness trainers, including Lacey Stone and Jorge Cruise, use red light therapy to enhance athletic performance and muscle recovery.

Supportive Cancer Care: The Multinational Association of Supportive Care in Cancer (MASCC) recommends the treatment of red light therapy for oral mucositis (OM), a common symptom of cancer treatment.

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Sources and References:

Klepeis N., Nelson W., Ott W., Robinson J., Tsang A., Switzer P., Behar J., Hern S., Engelmann W. “The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants”. Journal of Exposure Analysis and Environmental Epidemiology 2001.

Hamblin M. “Mechanisms and applications of the anti-inflammatory effects of photobiomodulation.” AIMS Biophys. 2017.

LED Lights Used in Plant Growth Experiments for Deep Space Missions. NASA.

Gál P,  Stausholm MB, et al. Should open excisions and sutured incisions be treated differently? A review and meta-analysis of animal wound models following low-level laser therapy. Lasers in Medical Science. 2018 Aug.

John Foley, David B Vasily, et al. 830 nm light-emitting diode (led) phototherapy significantly reduced return-to-play in injured university athletes: a pilot study. Laser Therapy. 2016 Mar.

Kim HK, Choi JH. Effects of radiofrequency, electroacupuncture, and low-level laser therapy on the wrinkles and moisture content of the forehead, eyes, and cheek. Journal of Physical Therapy Science. 2017 February.

Wunsch A and Matuschka K. A Controlled Trial to Determine the Efficacy of Red and Near-Infrared Light Treatment in Patient Satisfaction, Reduction of Fine Lines, Wrinkles, Skin Roughness, and Intradermal Collagen Density Increase. Photomedicine and Laser Surgery. Feb 2014.

Barolet D, Roberge CJ, et al. Regulation of skin collagen metabolism in vitro using a pulsed 660 nm LED light source: clinical correlation with a single-blinded study. Journal of Investigative Dermatology. 2009 December.

Morita T., Tokura H. “ Effects of lights of different color temperature on the nocturnal changes in core temperature and melatonin in humans” Journal of Physiological Anthropology. 1996, Sept.

Naeser M., Zafonte R, Krengel MH, Martin PI,  Frazier J, Hamblin MR, Knight JA, Meehan WP, Baker EH. “Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study”  Journal of Neurotrauma. 2014, June.

Liu KH, Liu D, et al. “Comparative effectiveness of low-level laser therapy for adult androgenic alopecia: a system review and meta-analysis of randomized controlled trials.” Lasers in Medical Science. 2019 Aug.

Gupta AK, Mays RR, et al. “Efficacy of non-surgical treatments for androgenetic alopecia: a systematic review and network meta-analysis.” JEADV. 2018 Dec.

Afifi L, Maranda EL, et al. “Low-level laser therapy as a treatment for androgenetic alopecia.” Lasers in Surgery and Medicine. 2017 Jan.

Hofling DB, Chavantes MC, et al. Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial. Lasers in Surgery and Medicine. May 2013.

Hofling DB, Chavantes MC, et al. Assessment of the effects of low-level laser therapy on the thyroid vascularization of patients with autoimmune hypothyroidism by color Doppler ultrasound. ISRN Endocrinology. 2012.

Hofling DB, Chavantes MC, et al. Low-level laser therapy in chronic autoimmune thyroiditis: a pilot study. Lasers in Surgery and Medicine. 2010 Aug.

Vladimirovich Moskvin S., Ivanovich Apolikhin O. Effectiveness of low level laser therapy for treating male infertility. Biomedicine (Taipei). 2018 June.

Ban Frangez H., Frangez I., Verdenik I., Jansa V., Virant Klun I. Photobiomodulation with light-emitting diodes improves sperm motility in men with asthenozoospermia. Laser in Medical Science, 2015 Jan.

Salman Yazdi, R., Bakhshi, S., Jannat Alipoor, F. et al. Effect of 830-nm diode laser irradiation on human sperm motility. Lasers Med Sci. 2014.

Chow KW, Preece D, Burns MW. Effect of red light on optically trapped spermatozoa. Biomedical Optics Express. 2017 Aug.

Preece D., Chow KW, Gomez-Godinez V., Gustafson K., et al. Red light improves spermatozoa motility and does not induce oxidative DNA damage. Scientific Reports. 2017 Apr.

American Psychiatric Association

Cassano P, Petrie SR, et al. Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial. Photomedicine and Laser Surgery. 2018 October.

Barrett DW, et al. Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. 2013 Jan.

Blanco NJ, Maddox WT, Gonzalez-Lima F. Improving executive function using transcranial infrared laser stimulation. Journal of Neuropsychology. 2017 Mar.

Paolillo FR, Borghi-Silva A, et al. New treatment of cellulite with infrared-LED illumination applied during high-intensity treadmill training. J Cosmet Laser Ther. 2011 Aug;13(4):166-71.

Caruso-Davis MK, Guillot TS, Podichetty VK, Mashtalir N, Dhurandhar NV, Dubuisson O, Yu Y. Efficacy of low-level laser therapy for body contouring and spot fat reduction. Obes Surg. 2011. Jun;21(6):722-9.

Jackson RF, Dedo DD, Roche GC, et al. Low-level laser therapy as a non-invasive approach for body contouring: a randomized, controlled study. Lasers in Surgery and Medicine. Dec 2009;41(10):99-809.

McRae E and Boris J. Independent evaluation of low-level laser therapy at 635 nm for non-invasive body contouring of the waist, hips, and thighs. Lasers in Surgery and Medicine. Jan 2013.

Avci P, Gupta A, et al. Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Seminars in Cutaneous Medicine and Surgery. Mar 2013; 32(1): 41-52.

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The first formal description of Seasonal Affective Disorder (SAD), the most well-known psychiatric condition associated with seasonality in humans, was introduced in the mid-1980s by Rosenthal, who described a group of 29 patients living in a temperate climate who experienced depressive episodes characterized by hypersomnia, hyperphagia, and weight gain in the fall or winter, and whose symptoms remitted by the next spring or summer.

SAD was incorporated into the Diagnostic and Statistical Manual (DSM) of Mental Disorders III-R when “seasonal pattern” was introduced as a specifier for Major Depression and Bipolar Disorders. Subsequent revision in DSM-IV described SAD as “a regular temporal relationship between the onset of Major Depressive Episodes in Bipolar I (BPI) or Bipolar II (BPII) Disorder or Major Depressive Disorder (MDD), recurrent, and a particular time of the year.”

Today, SAD, or MDD with seasonal pattern, is defined as recurrent episodes of major depression that meet the following criteria: at least two consecutive years where the onset and offset of depressive symptoms occur at characteristic times with no non-seasonal episodes, a temporal relationship between onset of symptoms and time of year, a temporal relationship between remission of symptoms and time of year, and an outnumbering of seasonal compared to non-seasonal episodes throughout the lifetime of the patient.

Pathophysiology of SAD

To date, the pathophysiology of SAD is unclear. Early research into the mechanism of SAD focused on day length or photoperiod. This hypothesis posited that shorter days in winter, possibly mediated by a longer duration of nocturnal melatonin secretion, leads to depressed mood in susceptible individuals. To date, there is little data to support this hypothesis. Furthermore, given that bright light in the evening has not been as effective as that given in the morning, it now seems unlikely that the photoperiod is the underlying pathological mechanism of SAD.

Although some animal studies have implicated a direct effect of light on the midbrain (Miller, Miller, Obermeyer, Behan, & Benca, 1999; Miller, Obermeyer, Behan, & Benca, 1998), the most prominent hypothesis driving human studies involves disruption of circadian rhythms. Research on the role of serotonin is also active.

Circadian Rhythm

A circadian rhythm refers to the approximately 24-hour cycle of physiological processes present in humans and other animals. This cycle is governed via clock gene expression by the suprachiasmatic nucleus (SCN), the master pacemaker located within the anterior hypothalamus. Though the SCN endogenously generates circadian oscillations, SCN endogenously generates circadian oscillations, and they need to be entrained to the 24-hour day by external cues. Light exposure is the most important synchronizing agent of endogenous circadian rhythms.

Downstream of the SCN, a collection of systemically active neurohumoral networks transduce circadian information to the rest of the body. For instance, via projections to the hypothalamus's paraventricular nucleus, the activation of the SCN leads to autonomic changes, including cardiovascular modulation, and together the central, peripheral, and autonomic nervous systems collaborate to affect systemic changes. Thus, the SCN receives information about the external day-night cycle directly through retinofugal pathways and indirectly through neuromodulatory signaling. Circadian information is then relayed systemically through neurohumoral networks.

The current primary hypothesis for the pathophysiology of SAD, known as the “phase-shift hypothesis,” posits that there is an optimal relationship in the alignment of the sleep-wake cycle and the endogenous circadian rhythm. During the fall and winter, as day length shortens, the circadian rhythm begins to drift later concerning clock time and the sleep-wake cycle. This phase delay is hypothesized to bring about mood symptoms. A pulse of morning bright light generates a circadian phase advance, which is thought to correct the discordance between sleep and circadian phase, thereby ameliorating depressive symptoms. However, the phase-shift hypothesis would predict that the amount of phase correction required for each patient would depend on an individual’s PAD, which has not yet been proven.

Serotonin

Several studies have also proposed that serotonin is implicated in the pathophysiology of SAD, as selective serotonin reuptake inhibitors (SSRIs) appear to be effective in the treatment of SAD. Supporting this hypothesis, one study used Positron Emission Tomography (PET) imaging to look at binding probability at synaptic serotonin transporters in 88 normal individuals living in the temperate climate of Toronto, Canada (Praschak-Rieder, Willeit, Wilson, Houle, & Meyer, 2008). The binding probability was increased during fall and winter compared to warmer months, thus eliciting an inverse correlation between binding potential and sunlight durationsunlight duration. Of note, the largest difference in transporter binding was found in the mesencephalon, a finding consistent with animal studies demonstrating the importance of direct effects of light to the midbrain on behavior. If increased transporter activity indicated greater reuptake of serotonin during the fall/winter, and if this resulted in a lower density of cleft serotonin, then the seasonal variation in transporter activity (i.e., higher transporter efficiency in the winter) would seem to leave susceptible individuals particularly prone to mood symptoms during the darker seasons. Moreover, following BLT and during periods of remission in the summer months, the synaptic transporter activity was shown to be reduced to control levels in these patients.

Eating Disorders

BLT has also been investigated to a lesser extent in eating disorders. Because binge eating episodes have been observed to increase in fall and winter in some patients, BLT has been examined as a treatment modality for anorexia nervosa (AN) and bulimia nervosa (BN). Thus, BLT's effects on patients with eating disorders remain enigmatic. Additional studies, including larger, randomized, blinded, and controlled trials, are needed to elucidate further the role of BLT in treating this patient population. Further research might also determine whether BLT would be a useful treatment in Binge-Eating Disorder, a diagnosis new to DSM-5.

Adult ADHD

Additionally, BLT has been studied in the context of adult Attention-Deficit/Hyperactivity Disorder (ADHD), where, in addition to normal ADHD symptoms, patients often have depressed mood and difficulties falling asleep, awakening on time, and maintaining arousal (Brown & McMullen, 2001). These symptoms are indicative of a possible delay in the circadian rhythm. A case report of symptom improvement following BLT in a child with ADHD who displayed signs of delayed sleep phase also supports the idea that BLT may be useful in treating symptoms of ADHD (Gruber, Grizenko, & Joober, 2007). Whether the pathways that subserve the improvement of mood symptoms in response to BLT are the same pathways that underlie the seemingly beneficial effects of BLT in ADHD remains to be studied. While these results are promising, further studies, preferably in randomized, blinded, and controlled studies will need to be performed.

Finally

A significant immediate reduction of depression scores with light treatment can be identified after 20 minutes and reaches the maximum at 40 minutes, with no additional benefit at 60 minutes. The rate of change is steepest during the first 20 minutes of light as compared with longer intervals. Comparing the clinical impact of these durations of administration may yield different results when measured after several daily sessions. The overnight effect on circadian rhythms and sleep was not assessed in our study and is thought to impact mood regulation in SAD. Larger, prospective, controlled, and hypothesis-driven studies in more naturalistic conditions would be desirable to replicate our study results and our study results and analyze the temporal dynamic of the persistence of the immediate mood-improvement effects. Besides, in larger samples, one could define early responders and nonresponders, analyze genetic (e.g., melanopsin related genes), demographic (children, adolescents, adults, elderly, gender), physiological (e.g., pupillary responses), and clinical (e.g., abundant atypical symptoms) predictors for early response. If proven effective and efficacious, shorter exposures to bright light could become a feasible and broadly employed intervention for immediate mood improvement as an early step on the road toward full antidepressant response and remission.