Introduction: Plasma medicine is a novel, exciting, young interdisciplinary scientific
field, emerging from the interaction of physicists, biologists, and medical doctors.
Plasma is the fourth matter, often defined as an ionized gas produced by the
disintegration of polyatomic gas molecules or the removal of electrons from monatomic gas
shells, with the following strict criteria: plasma must be a) macromolecularly neutral
(quasi-neutrality); b) Debye shielding; c) frequency. As a result, plasma can be defined
as "a quasi-neutral gas containing many interacting free electrons and ionized atoms and
molecules, which have collective behavior caused by long-range coulomb forces", and their
motion gives rise to electric fields and generates currents and magnetic fields. Plasma
is classified into high-temperature, thermal, and non-thermal categories. In high
temperature, all particles (both electrons and heavy particles) have the same
temperature, and are thus in thermal equilibrium. Non-thermal (non-equilibrium) plasma
engulfs particles that are not in thermal equilibrium. This plasma is termed "cold
plasma". Cold plasma discharge can be achieved at both low pressure and atmospheric
pressure. Low pressure cold plasma was first applied for surface decontamination in a
more effective manner than conventional sterilization in the 1960s; by contrast, Cold
Atmospheric Plasma (CAP) was applied in 1990s.

CAP is ideal for use in modern medicine because : a) it can be generated easily from a
portable device with easier direct access to affected cells and tissues, b) all animal
and human tissues contain water and its presence is undesirable in low pressure
conditions, c) its ability to reduce microbial load makes it a good option to combat
increasing antibiotic resistance, and d) CAP-generating devices have relatively low
manufacturing costs. As a result, accessible, efficient, and inexpensive CAP devices can
reduce the financial burden imposed on the health budget by conventional treatments.

All plasma devices used in clinical practice are intended to prevent harm to healthy
cells. They undergo multistep testing and are associated with no significant side
effects. Nevertheless, the proper CAP dosage must be continuously monitored, adjusted for
each treatment, with an important parameter to be the distance between the plasma jet
source and human skin. Hypothetically speaking, it could not be excluded that CAP does
not have some minimal negative effects at the molecular level; these are still subject to
ongoing analysis, but results so far suggest that hypothetically unproven adverse effects
are outweighed by the enormous benefits of CAP.

Current analyses of CAP effects have concentrated mostly on cells in culture and animal
models. Although these efforts are more accessible and easier to conduct, wider testing
of CAP effects in disease and regenerative medicine studies in human patients could only
be beneficial. Nowadays, CAP is mostly employed in aesthetic procedures; however, its use
in more serious medical conditions, such as acute and chronic wounds, oral bacterial
infections, and potentially in tumour therapy, is subject to ongoing research. The use of
CAP in routine clinical practice in medicine could advance the therapeutic process into a
less invasive and distressing process for patients, while also significantly reducing the
financial burden of existing treatments in Europe and worldwide.

Aim of the Study: This cross-over single-blinded study evaluates the effect of a novel
CAP jet-producing device, the Human Regenerator Power Jet (CE 2022), for individuals who
suffer from chronic stress, chronic pain, chronic fatigue, sleep disorders, and
Post-COVID/Long-COVID Syndrome, all conditions that affect the QoL among adults in Greece
and worldwide [HR-QoL].

Participants: The HR-QoL study has solicited 40 participants randomized into two groups
(A & B). Group A (20 adults) was treated at the HR under CAP conditions (CAP Effect) (10
sessions), followed by a 1-month wash-out period, before treatment at the HR under AIR
Conditions (Sham Device-Placebo Effect). Group B (20 adults) was treated at the HR under
AIR conditions (Sham Device-Placebo Effect) followed by a 1-month wash-out period, before
treatment at the HR under CAP Conditions (Cap Effect). The participants were not aware
whether they were subjected to CAP or AIR from the device. The HR-QoL study was conducted
among adult residents of Greece, according to the World Medical Association Declaration
of Helsinki (2013). In the HR-QoL study, "adults" are defined as individuals no younger
than 18 years old. The eligible list of participants has been evaluated by the Endocrine
Unit of the University of Athens (NKUA).