Silicone and rubber oxygen masks are heavier than plastic masks. They are designed to provide a good seal for long-duration use by  aviators , medical research subjects, and  hyperbaric chamber  and other patients who require administration of pure oxygen, such as  carbon monoxide poisoning  and  decompression sickness  victims. Dr.  Arthur H. Bulbulian  pioneered the first modern viable oxygen mask, worn by World War II pilots and used by hospitals. [ 2 ]   Valves  inside these tight-fitting masks control the flow of gases into and out of the masks, so that rebreathing of exhaled gas is minimised.


Hoses or tubing connect an oxygen mask to the oxygen supply. Hoses are larger in diameter than tubing and can allow greater oxygen flow. When a hose is used it may have a ribbed or corrugated design to allow bending of the hose while preventing twisting and cutting off the oxygen flow. The quantity of oxygen delivered from the storage tank to the oxygen mask is controlled by a valve called a  regulator . Some types of oxygen masks have a breathing bag made of plastic or rubber attached to the mask or oxygen supply hose to store a supply of oxygen to allow deep breathing without waste of oxygen with use of simple fixed flow regulators.


An early 1919 high-altitude oxygen system used a vacuum flask of liquid oxygen to supply two people for one hour at 15,000 ft (4,600 m). The liquid passed through several warming stages before use, as expansion when it evaporated, and absorbed  latent heat of vaporization , would make the gasified oxygen so cold that it could cause instant  frostbite  of the lungs. [ 3 ]


The first successful creation for the oxygen mask was by Armenian born  Dr. Arthur Bulbulian , in the field of facial prosthetics, in 1941. [ citation needed ]


Many designs of aviator's oxygen masks contain a microphone to transmit speech to other crew members and to the aircraft's radio. Military aviators' oxygen masks have face pieces that partially cover the sides of the face and protect the face against flash burns, flying particles, and effects of a high speed air stream hitting the face during emergency evacuation from the aircraft by  ejection seat  or  parachute . They are often part of a  pressure suit  or intended for use with a  flight helmet .


Three main kinds of oxygen masks are used by  pilots  and crews who fly at high altitudes: continuous flow, diluter demand, and pressure demand. [ 4 ]


In a  continuous-flow system , oxygen is provided to the user continuously. It does not matter if the user is exhaling or inhaling as oxygen is flowing from the time the system is activated. Below the oxygen mask is a rebreather bag that collects oxygen during exhalation and as a result allows a higher flow rate during the inhalation cycle. [ 5 ]


Diluter-demand  and  pressure-demand  masks supply oxygen only when the user inhales. [ 6 ]  They each require a good seal between the mask and the user's face.


In a  diluter-demand system,  as the altitude increases (ambient pressure, and therefore the partial pressure of ambient oxygen, decreases), the oxygen flow increases such that the partial pressure of oxygen is roughly constant. Diluter-demand oxygen systems can be used up to 40,000 ft (12,000 m). [ 5 ]


In a  pressure-demand system , oxygen in the mask is above ambient pressure, permitting breathing above 40,000 feet (12,000 m). [ 5 ]  Because the pressure inside the mask is greater than the pressure around the user's torso, inhalation is easy, but exhalation requires more effort. Aviators are trained in pressure-demand breathing in  altitude chambers . Because they seal tightly, pressure-demand-type oxygen masks are also used in hyperbaric oxygen chambers and for oxygen breathing research projects with standard oxygen regulators. [ 2 ]


Supplemental oxygen is needed for flying more than 30 minutes at cabin pressure altitudes of 12,500 feet (3,800 m) or higher, pilots must use oxygen at all times above 14,000 feet (4,300 m) and each occupant must be provided supplemental oxygen above 15,000 feet (4,600 m). [ 7 ]


Most  commercial aircraft  are fitted with oxygen masks for use when cabin pressurization fails. [ 8 ] [ 9 ]  In general, commercial aircraft are  pressurized  so that the cabin air is at a pressure equivalent to no more than 8,000 feet (2,400 m) altitude (usually somewhat lower altitude), where one can breathe normally without an oxygen mask. If the oxygen pressure in the cabin drops below a safe level, risking  hypoxia , compartments containing the oxygen masks will open automatically, either above or in front of the passenger and crew seats, and in the lavatories.


In the early years of commercial flight, before  pressurized cabins  were invented, airliner passengers sometimes had to wear oxygen masks during routine flights.


Firefighters  and  emergency service  workers use full face masks that provide breathing air as well as eye and face protection. [ 10 ]  These masks are typically attached to a tank carried upon the back of the wearer and are called  self-contained breathing apparatuses  (SCBA). [ 11 ]  Open circuit SCBAs do not normally supply oxygen, as it is not necessary and constitutes an easily avoidable fire hazard. Rebreather SCBAs usually supply oxygen as this is the lightest and most compact option, and uses a simpler mechanism than other types of rebreather.


Specialized full-face masks that supply oxygen or other  breathing gases  are used by  astronauts  to remove nitrogen from their blood before  space walks  (EVA). [ citation needed ]


Specialized snout masks which supply oxygen to revive family  pets  have been donated to  fire departments . [ 12 ] [ 13 ] [ 14 ]


Divers only use pure oxygen for  accelerated decompression , or from oxygen  rebreathers  at shallow depths where the risk of acute  oxygen toxicity  is acceptable. Oxygen supply during in-water decompression is via rebreather,  open circuit diving regulator ,  full-face mask  or  diving helmet  which has been prepared for  oxygen service . [ 15 ]


Oxygen supply to divers in  decompression chambers  is preferably through a built-in breathing system, which uses an oxygen mask plumbed into supply and exhaust hoses which supply oxygen from outside the chamber, and discharge the exhaled oxygen-rich gas outside the chamber, using a system equivalent to two  demand valves , one upstream of the diver, to supply oxygen on demand, and the other downstream, to exhaust exhaled gas on demand, so that the oxygen partial pressure in the chamber is limited to relatively safe levels. If oxygen masks are used that discharge into the chamber, the chamber air must be replaced frequently to keep the oxygen level within safe operating limits. [ 16 ]


Anesthesia masks are face masks that are designed to administer  anesthetic  gases to a patient through inhalation. Anesthesia masks are either made of anti-static silicone or rubber, as a static electricity spark may ignite some anesthetic gases. They are either black rubber or clear silicone. Anesthesia masks fit over the mouth and nose and have a double hose system. One hose carries inhaled anesthetic gas to the mask and the other brings exhaled anesthetic gas back to the machine. Anesthesia masks have 4 point head strap harnesses to securely fit on the head to hold the mask in place as the anaesthetist controls the gases and oxygen inhaled.


Oxygen masks are used by  climbers  of high peaks such as  Mount Everest . [ 17 ]  Because of the severe cold and harsh conditions oxygen masks for use at extreme altitude must be robust and effective. The oxygen storage tanks used with the masks (called oxygen bottles) are made of lightweight, high-strength metals and are covered in high-strength fiber such as  kevlar . These special oxygen bottles are filled with oxygen at a very high pressure which provides a longer time duration of oxygen for breathing than standard pressure oxygen bottles. These systems are generally only used above 7,000 metres (23,000 ft).


In recent years oxygen mask systems for high-altitude climbing which pump oxygen constantly have been increasingly replaced by systems supplying oxygen on demand via  nasal cannulas . [ citation needed ]


Oxygen helmets are used in  hyperbaric oxygen  chambers for oxygen administration. [ 2 ]  They are transparent, lightweight plastic helmets with a seal that goes around the wearer's neck that looks like a  space suit   helmet . They offer a good visual field. Light weight plastic hoses provide oxygen to the helmet and remove exhaled gas to the outside of the chamber. Oxygen helmets are often preferred for oxygen administration in hyperbaric oxygen chambers for children and patients that are uncomfortable wearing an oxygen mask. [ citation needed ]


Medical oxygen masks are held in place by medical personnel or the user by hand, or they may be fitted with a lightweight elastic headband so the mask can be removed quickly. Full-face masks are secured by several straps. Tightly fitting oxygen masks are secured at four points by two head straps. Aviators' masks are often equipped with "quick don" harnesses that allow those in pressurized aircraft to rapidly don the masks in emergencies. Military aviators' oxygen masks are secured to flight helmets with quick-release systems.


In  physics , a  paste  is a substance that behaves as a  solid  until a sufficiently large load or  stress  is applied, at which point it flows like a  fluid . In  rheological  terms, a paste is an example of a  Bingham plastic   fluid .


Pastes typically consist of a  suspension  of  granular material  in a background fluid.  The individual grains are jammed together like  sand  on a  beach , forming a disordered,  glassy  or  amorphous  structure, and giving pastes their solid-like character.  It is this "jamming together" that gives pastes some of their most unusual properties; this causes paste to demonstrate properties of  fragile matter .


Examples include  starch  pastes,  toothpaste ,  mustard , and  putty .


In pharmacology,  paste  is a basic  pharmaceutical form . It consists of a fatty base (e.g.,  petroleum jelly ) and at least 25% of a solid substance (e.g.,  zinc oxide ). Pharmaceutical pastes are typically intended for external application to the skin. They are usually thick and do not melt at physiologic temperatures. [ 1 ]


This  material -related article is a  stub . You can help Wikipedia by  expanding it .


A  pessary  is a prosthetic device inserted into the  vagina  for structural and pharmaceutical purposes. It is most commonly used to treat  stress urinary incontinence  to stop urinary leakage and to treat  pelvic organ prolapse  to maintain the location of organs in the pelvic region. [ 1 ]  It can also be used to administer medications locally in the vagina or as a method of  contraception .


Pessaries come in different shapes and sizes, so it is important that individuals be fitted for them by health care professionals to avoid any complications. [ 1 ]  However, there are a few instances and circumstances that allow pessaries to be purchased without a prescription or without seeking help from a health care professional. [ 2 ]  Some side effects may occur if pessaries are not sized properly or regularly maintained, but with the appropriate care, pessaries are generally safe and well tolerated. [ 3 ]


Early use of pessaries dates back to the ancient Egyptians, as they described using pessaries to treat pelvic organ prolapse. [ 3 ]  The term 'pessary' itself, is derived from the Ancient Greek word 'pessós', meaning round stone used for games. [ 4 ] [ 5 ]  Pessaries are even mentioned in the oldest surviving copy of the Greek medical text,  Hippocratic Oath , as something that physicians should never administer for the purposes of an abortion: "Similarly I will not give to a woman a pessary to cause abortion." [ 6 ]  The earliest documented pessaries were natural products. For example, Greek physicians  Hippocrates  and  Soranus  described inserting half of a pomegranate into the vagina to treat prolapse. [ 3 ]  It was not until the 16th century that the first purpose-made pessaries were made. [ 5 ]  For instance, in the late 1500s,  Ambroise Paré  was described as making oval pessaries from hammered brass and waxed cork. Nowadays, pessaries are generally made from silicone and are well tolerated and effective among patients who need them. [ 3 ]


The most common use for pessaries is to treat pelvic organ prolapse. A pelvic organ prolapse can occur when the muscles and tissues surrounding the bladder, uterus, vagina, small bowel, and rectum stop working properly to hold the organs in place and the organs begin to drop outside the body. The most common cause of such prolapse is childbirth, usually multiple births.  Obesity , long-term respiratory problems,  constipation , pelvic organ cancers, and  hysterectomies  can all be causes for pelvic organ prolapses as well. [ 7 ]  Some signs and symptoms include feeling pressure in the pelvic area, lower back pain, painful intercourse, urinary incontinence, a feeling that something is out of place, constipation, or bleeding from the vagina. [ 7 ]  Pessaries are manual devices that are inserted into the vagina to help support and reposition descended pelvic organs, which helps to prevent the worsening of prolapse, helps with symptom relief, and can delay or prevent the need for surgery. [ 3 ] [ 5 ]  Further, pessaries can be used for surgery preparation as a way to maintain prolapse without progression. [ 3 ]  This is especially useful when a surgery may need to be delayed. [ 3 ]


Stress urinary incontinence is leakage of urine that is caused by sudden pressure on the bladder. It occurs during activities that increase the amount of pressure on the bladder such as coughing, sneezing, laughing, and exercising. [ 8 ]  The pressure causes opening of the  sphincter muscles  which usually help prevent urine leakage. Stress urinary incontinence is a common medical problem especially in women as about 1 in 3 women are affected by this condition at some point in their lives. [ 8 ]   Pessaries are considered a safe non-surgical treatment option for stress urinary incontinence as it can control the urine leakage by pushing the  urethra  closed. Pessaries can be removed any time. [ 8 ] [ 9 ]


Some additional uses for pessaries are for an  incarcerated uterus , prevention of  preterm birth  and an incompetent  cervix . [ 3 ] [ 10 ]  In early pregnancy the  uterus  can be displaced, which can lead to pain and rectal and urinary complications. [ 3 ]  A pessary can be used to treat this condition and support the uterus. [ 3 ]  Preterm birth is when babies are born prematurely, which puts the baby at increased risk for complications and even death. Currently, the use of pessaries to help prevent preterm birth is an ongoing area of research. [ 10 ]  The use of pessaries for an incompetent cervix is not commonly practiced today, but they have been used in the past. [ 3 ]  Specifically, an incompetent cervix is when the cervix begins to open up prematurely. [ 11 ]  This can lead to a preterm birth or even a miscarriage. Pessaries can be used to correctly position the cervix, increasing the success of pregnancy. [ 3 ]


A  therapeutic pessary  is a medical device similar to the outer ring of a  diaphragm . Therapeutic pessaries are used to support the  uterus ,  vagina ,  bladder , or  rectum . [ 12 ]  Pessaries are most commonly used for pelvic organ prolapse and considered a good treatment option for women who need or desire non-surgical management or future pregnancy. [ 12 ]  It is used to treat  prolapse of uterine , vaginal wall ( vaginal vault ), bladder ( cystocele ), rectum ( rectocele ), or small bowel ( enterocele ). It is also used to treat  stress urinary incontinence . [ 13 ]


There are different types of pessaries but most of them are made out of silicone—a harmless and durable material. [ 14 ]  Pessaries are mainly categorized into two types, supporting pessaries and space-occupying pessaries. [ 5 ]  Support pessaries function by supporting the prolapse and space-occupying pessaries by filling the vaginal space. [ 3 ]  There are also lever type pessaries. [ 15 ]


Ring with support pessaries  are the supporting type. [ 5 ]  These are often used as a first-line treatment and used for earlier stage prolapse since individuals can easily insert and remove them on their own without a doctor's help. These can be easily folded in half for insertion. [ 12 ] [ 14 ]


Gellhorn pessaries  are considered a type of supporting and space-occupying pessary. [ 5 ]  These resemble the shape of a mushroom and are used for more advanced pelvic organ prolapse. [ 5 ] [ 14 ]  These are less preferred than ring with support pessaries due to difficulty with self-removal and insertion. [ 14 ]


Marland pessaries  are another type of supporting pessary. [ 12 ]  These are used to treat pelvic organ prolapse as well as stress urinary incontinence. [ 12 ]  These pessaries have a ring at their base and a wedge-shaped ridge on one side. [ 14 ]  Although these pessaries are less likely to fall out than standard ring with support pessaries, individuals find it difficult to insert or remove them on their own. [ 14 ]


Donut pessaries  are considered space-occupying pessaries. [ 5 ]  These are used for more advanced pelvic organ prolapse including cystocele or rectocele as well as a second or third-degree uterine prolapse. [ 12 ]  Due to its shape and size, it is one of the hardest ones to insert and remove. [ 14 ]


Cube pessaries  are space-occupying pessaries in the shape of a cube that are available in 7 sizes. The pessary is inserted into the vagina and kept in place by the suction of its 6 surfaces to the vaginal wall. Cube pessaries must be removed before sexual intercourse and replaced daily. [ 5 ]  Cube pessaries are generally used as a last resort only if the individuals cannot retain any other pessaries. [ 3 ]  This is due to undesirable side effects such as vaginal discharge and erosion of the vaginal wall. [ 3 ] [ 5 ]  In order to remove the cube pessary, the suction must be broken by grasping the device. [ 3 ]


Gehrung pessaries  are space-occupying pessaries that are similar to the Gellhorn pessaries. [ 3 ]  They are silicone devices that are placed into the vagina and used for second or third degree (more severe) uterine prolapse. These contain metal and should be removed prior to any MRI, ultrasound or X-rays. They can also be used to help with stress urinary incontinence such as urine leaks during exercising or coughing. These types of pessaries need to be fitted by a health care professional to ensure proper size. Once placed it should not move when standing, sitting, or squatting. It should be cleaned with mild soap and warm water every day or two. [ 16 ]


Hodge pessaries  are a type of lever pessary. Although these can be used for mild  cystocele  and stress urinary incontinence, they are not commonly used. Smith, and Risser pessaries are other types of lever pessaries and they differ in shape. [ 14 ] [ 15 ]


Treating vaginal yeast infections is one of the most common uses of pharmaceutical pessaries. They are also known as vaginal  suppositories , which are  inserted into the vagina  and are designed to dissolve at body temperature. They usually contain a single use antifungal agent such as  clotrimazole . Oral antifungal agents are also available. [ 17 ]


Pessaries can also be used in a similar way to help induce labor for women who have overdue expected delivery dates or who experience premature rupture of membranes.  Prostaglandins  are usually the medication used in these kinds of pessaries in order to relax the cervix and promote contractions. [ 18 ]


According to  Pliny the Elder , pessaries were used as birth control in ancient times. [ 19 ]


Occlusive pessaries are most commonly used for contraception. Also known as a contraceptive cap, they work similar to a diaphragm as a barrier form of contraception. They are inserted into the vagina and block sperm from entering the uterus through the cervix. The cap must be used in conjunction with a spermicide in order to be effective in preventing pregnancy. When used correctly the cap is thought to be 92–96% effective. These caps are reusable but come in different sizes. It is recommended for anyone attempting this form of contraception to be fitted for the correct size by a trained health care professional. [ 20 ]


The stem pessary, a type of occlusive pessary, was an early form of the  cervical cap . Shaped like a dome, it covered the cervix, and a central rod or "stem" entered the uterus through the external orifice of the uterus, also known as the cervical canal or the  os , to hold it in place. [ 21 ]


When pessaries are used correctly, they are tolerated well for pelvic organ prolapse or stress urinary incontinence. [ 22 ]  However, pessaries are still a foreign device that is inserted into the vagina, so side effects can occur. [ 23 ]  Some more common side effects include vaginal discharge and odor. [ 12 ]  Vaginal discharge and odor may be associated with  bacterial vaginosis , characterized by an overgrowth of naturally occurring bacteria in the vagina. [ 24 ]  These symptoms can be treated with the appropriate medications.


More serious side effects include  fistula  formation between the vagina and rectum or the vagina and bladder, or erosion, or thinning, of the vaginal wall. [ 12 ]  Fistula formation is rare, but erosion of the vaginal wall occurs more frequently. Low estrogen production can also increase the risk of vaginal wall thinning. [ 25 ]  For individuals with pessaries that are not fitted for them,  herniations  of the cervix and uterus can occur through the opening of the pessary. This can lead to tissue necrosis in the cervix and uterus. [ 23 ]  To prevent these side effects, individuals can be fitted properly for their pessaries and undergo routine follow-up visits with their health care professionals to ensure the individual has the correct pessary size and no other complications. [ 12 ]  In addition, those with an increased risk of vaginal wall thinning can be prescribed estrogen to prevent erosion and prevent these complications. [ 3 ]


If pessaries are not used properly or not maintained periodically, more serious complications can occur. For example, the pessary can become embedded into the vagina, which makes it harder to remove. Estrogen can decrease the inflammation of the vaginal walls and promote skin cells in the vagina to mature, so use of estrogen cream can allow removal of the pessary more easily. [ 23 ]  In rare cases, pessaries would need to be removed through surgical procedures. [ 3 ]


To prevent complications, individuals should not use pessaries if they have characteristics that exclude them from this method of therapy.  Contraindications  to pessary use include current infections in the pelvis or vagina, or allergies to the material of the pessary (which can be silicone or latex). [ 13 ]  In addition, individuals should not be fitted for a pessary if they are less likely to properly maintain their pessary.


Gholam A. Peyman  (born 1 January 1937) is an  Iranian American   ophthalmologist ,  retina  surgeon, and inventor. He is best known for his invention of  LASIK  eye surgery, [ 2 ]  a vision correction procedure designed to allow people to see clearly without glasses. He was awarded the first US patent for the procedure in 1989.


Peyman was born in  Shiraz ,  Iran . At the age of 19, he moved to Germany to begin his medical studies. He received his MD at the  University of Freiburg  in 1962. [ citation needed ]  He completed his internship at St. Johannes Hospital in Duisburg, Germany in 1964 and at Passaic General Hospital in  Passaic, New Jersey  in 1965. [ citation needed ]  Peyman completed his residency in ophthalmology and a retina fellowship at the University of Essen, Essen Germany, in 1969 and an additional postdoctoral fellowship in retina at the  Jules Stein Eye Institute , UCLA School of Medicine in Los Angeles in 1971. Peyman held the position of assistant professor of ophthalmology at the  UCLA  School of Medicine from 1971 and served as associate professor and then professor of ophthalmology and ocular oncology at the  Illinois Eye and Ear Infirmary ,  University of Illinois at Chicago  during 1971–1987. [ citation needed ]


Peyman held a joint appointment at the School of Medicine and also at the Neuroscience Center of Excellence at the Louisiana State University Medical University Medical Center in New Orleans during 1987–2000. During 1998-2000 Peyman held the Prince Abdul Aziz Bin Ahmed Bin Abdul Aziz Al Saud Chair in Retinal Diseases. During 2000–2006, Peyman served as professor of ophthalmology, ocular oncology and co-director, Vitreo-Retinal Service,  Tulane University School of Medicine  in New Orleans. [ citation needed ]


During 2006–2007, he was professor of ophthalmology at the  University of Arizona, Tucson , with a cross appointment at  University of Arizona College of Optical Sciences . He has been emeritus professor of ophthalmology at Tulane University since 2009. [ citation needed ]


Peyman is currently professor of basic medical sciences at the  University of Arizona College of Medicine – Phoenix  & Optical engineering at the University of Arizona in Tucson.
Peyman was awarded in 2013 an honoree doctorate degree from the  National University of Cordoba  in  Argentina . [ 3 ]


At the  Illinois Eye and Ear Infirmary , Peyman, because of his interest in the effects of lasers on tissues in the eye, began evaluating the potential use of a CO 2  laser to modify corneal refraction in rabbits. No prior study had existed on this concept. The laser was applied to the surface of the cornea using different patterns. This laser created significant scarring. His conclusions at that time were: 1) one has to wait for the development of an ablative laser and 2) one should not ablate the surface of the cornea but, instead, the ablation should take place under a flap in order to prevent scarring, pain and other undesirable sequelae. Peyman published the first article on this subject in 1980. [ 4 ]


In late 1982, he read an article from IBM Laboratories, published in  Laser Focus , describing the photo-ablative properties of an excimer laser on organic material. This was very exciting information, but, unfortunately, Peyman did not have access to this laser, which at the time was new and very expensive. By 1985 and beyond, many investigators were interested in ablating the corneal surface. However, because of his previous experience with the CO 2  laser, Peyman wanted to avoid surface ablation in order to prevent potential corneal scarring and the pain associated with the removal of the corneal epithelium, necessary to expose the surface of the cornea. Therefore, in July 1985, he applied for a patent that described a method of modifying corneal refractive errors using laser ablation under a corneal flap. This US patent was accepted after two revisions and issued in June, 1989. Peyman performed a number of experimental studies evaluating the effect of various excimer lasers in collaboration with Physics Department of the University of Helsinki, Finland. Since he had purchased an Erb-Yag laser in the U.S., he evaluated the concept using this laser  in vivo  in rabbit and primate eyes and described the creation of a hinged corneal flap to enable the ablation to be performed on the exposed corneal bed, thus reducing the potential for postoperative scarring and pain. [ 5 ]


Always aware of the potential limitations of his invention, Peyman devoted considerable time and effort in subsequent years to ameliorating them. In order to improve the risk/benefit considerations of the LASIK procedure, he invented in 2004 and patented a broad range of ablative and non-ablative inlays to be placed under the surgically created corneal flap (US Patent 6,702,807). These inlays offered many potential advantages over the standard LASIK technique, the most significant of which is that the inlay procedure is reversible. [ 6 ]


However, their ablation was not predictable. In October 2009, Peyman invented and applied for a patent on a method of preventing corneal implant rejection, which was approved in 2017 (US Patent 9,681,942).  It consisted of forming a Lasik flap in the cornea, raising the flap, inserting a lamellar cornea under the flap so as to overlie the exposed stromal tissue. The inlay is ablated with wavefront guided excimer laser, to correct the refractive errors of the eye, applying a cross linking solution to the inlay and stromal tissue of the cornea, replacing the corneal flap and cross linking the inlay with UV radiation, killing the cellular elements in the inlay and its surrounding cornea, preventing cellular migration in the inlay and its rejection or encapsulation by the host corneal cells.  This new procedure is now called “Mesoick” (Meso means Inside, Implant, Crosslinking Keratomileusis (US Patent 9,037,033). This creates an immune privileged cell free space that does not initiate an immune response to an implant. A synthetic, crosslinked organic or polymeric lens can be implanted in the corneal pocket to compensate for the patient's refractive error. The implant can be exchanged as the eye grows or refractive need dictates. [ 7 ]


Peyman has been granted 200 US  Patents [ 8 ]  covering a broad range of novel medical devices, intra-ocular drug delivery, surgical techniques, as well as new methods of diagnosis and treatment.


Development of direct intraocular drug delivery and Vitrectomy


Surgical removal of intraocular tumors


This technology enables an ophthalmologist to treat a patient located in another location e.g. another city by a laser system controlled remotely, via the internet, using a sophisticated secure system in a non-contact fashion.


Development of precision thermotherapy in oncology
Therapy of malignant tumors in early-stage along with imaging and immune therapy and precision localized drug delivery:


Tele-laser system and tele- medicine with a novel Dynamic Identity recognition


Macular degeneration


Intravitreal slow-release Rock inhibitors alone or in combination with Anti-VEGF


Artificial Retina Stimulation


Quantum dots and Optogenetic for artificial retinal and brain stimulation and gene therapy


Gene therapy with non-viral nanoparticles and CRISPR


Adaptic optic phoropter for automated vision correction and Tunable light field camera in use for VR and AR technology


Among other awards and honors, Peyman has received the  National Medal of Technology and Innovation  (2012), [ 18 ]  the Waring Medal of the  Journal of Refractive Surgery  (2008), [ 19 ]  and the  American Academy of Ophthalmology 's Lifetime Achievement Award (2008) [ 20 ]  He was named a fellow of the  National Academy of Inventors  in 2013. [ 21 ]


Photosensitizers  are light absorbers that alter the course of a  photochemical reaction .  They usually are  catalysts . [ 1 ]   They can function by many mechanisms, sometimes they donate an electron to the substrate, sometimes they abstract a hydrogen atom from the substrate. At the end of this process, the photosensitizer returns to its  ground state , where it remains chemically intact, poised to absorb more light. [ 2 ] [ 3 ] [ 4 ]  One branch of chemistry which frequently utilizes photosensitizers is  polymer chemistry , using photosensitizers in reactions such as  photopolymerization , photocrosslinking, and  photodegradation . [ 5 ]  Photosensitizers are also used to generate prolonged excited electronic states in organic molecules with uses in  photocatalysis ,  photon upconversion  and  photodynamic therapy . Generally, photosensitizers absorb  electromagnetic radiation  consisting of  infrared radiation ,  visible light radiation , and  ultraviolet radiation  and transfer absorbed energy into neighboring molecules. This absorption of light is made possible by photosensitizers' large  de-localized π-systems , which lowers the energy of  HOMO and LUMO  orbitals to promote  photoexcitation . While many photosensitizers are organic or organometallic compounds, there are also examples of using semiconductor  quantum dots  as photosensitizers. [ 6 ]


Photosensitizers absorb light (hν) and transfer the energy from the  incident light  into another nearby molecule either directly or by a chemical reaction.  Upon absorbing  photons  of radiation from incident light, photosensitizers transform into an excited  singlet state . The single electron in the excited  singlet state  then flips in its intrinsic spin state via  Intersystem crossing  to become an excited  triplet state . Triplet states typically have longer lifetimes than excited singlets. The prolonged lifetime increases the probability of interacting with other molecules nearby. Photosensitizers experience varying levels of efficiency for intersystem crossing at different wavelengths of light based on the internal electronic structure of the molecule. [ 2 ] [ 7 ]


For a molecule to be considered a photosensitizer:


It is important to differentiate photosensitizers from other  photochemical  interactions including, but not limited to,  photoinitiators ,  photocatalysts ,  photoacids  and  photopolymerization . Photosensitizers utilize light to enact a chemical change in a substrate; after the chemical change, the photosensitizer returns to its initial state, remaining chemically unchanged from the process.  Photoinitiators  absorb light to become a reactive species, commonly a  radical  or an  ion , where it then reacts with another chemical species. These photoinitiators are often completely chemically changed after their reaction.  Photocatalysts  accelerate chemical reactions which rely upon light. While some photosensitizers may act as photocatalysts, not all photocatalysts may act as photosensitizers.  Photoacids  (or photobases) are molecules which become more acidic (or basic) upon the absorption of light. Photoacids increase in acidity upon absorbing light and thermally reassociate back into their original form upon relaxing.  Photoacid generators  undergo an irreversible change to become an acidic species upon light absorption.  Photopolymerization  can occur in two ways. Photopolymerization can occur directly wherein the monomers absorb the incident light and begin polymerizing, or it can occur through a photosensitizer-mediated process where the photosensitizer absorbs the light first before transferring energy into the monomer species. [ 8 ] [ 9 ]


Photosensitizers have existed within natural systems for as long as  chlorophyll  and other light sensitive molecules have been a part of plant life, but studies of photosensitizers began as early as the 1900s, where scientists observed photosensitization in biological substrates and in the treatment of cancer. Mechanistic studies related to photosensitizers began with scientists analyzing the results of chemical reactions where photosensitizers  photo-oxidized  molecular oxygen into peroxide species. The results were understood by calculating quantum efficiencies and fluorescent yields at varying wavelengths of light and comparing these results with the yield of  reactive oxygen species . However, it was not until the 1960s that the electron donating mechanism was confirmed through various  spectroscopic  methods including reaction-intermediate studies and  luminescence  studies. [ 8 ] [ 10 ] [ 11 ]


The term photosensitizer does not appear in scientific literature until the 1960s. Instead, scientists would refer to photosensitizers as sensitizers used in photo-oxidation or photo-oxygenation processes. Studies during this time period involving photosensitizers utilized organic photosensitizers,  consisting of  aromatic hydrocarbon  molecules, which could facilitate synthetic chemistry reactions. However, by the 1970s and 1980s, photosensitizers gained attraction in the scientific community for their role within biologic processes and enzymatic processes. [ 12 ] [ 13 ]  Currently, photosensitizers are studied for their contributions to fields such as energy harvesting,  photoredox catalysis  in synthetic chemistry, and cancer treatment. [ 11 ] [ 14 ]


There are two main pathways for photosensitized reactions. [ 15 ]


In Type I photosensitized reactions, the photosensitizer is excited by a light source into a triplet state. The excited, triplet state photosensitizer then reacts with a substrate molecule which is not molecular oxygen to both form a product and reform the photosensitizer. Type I photosensitized reactions result in the photosensitizer being quenched by a different chemical substrate than molecular oxygen. [ 2 ] [ 16 ]


In Type II photosensitized reactions, the photosensitizer is excited by a light source into a triplet state. The excited photosensitizer then reacts with a ground state,  triplet oxygen  molecule. This excites the oxygen molecule into the singlet state, making it a  reactive oxygen species . Upon excitation, the  singlet oxygen  molecule reacts with a substrate to form a product. Type II photosensitized reaction result in the photosensitizer being quenched by a ground state oxygen molecule which then goes on to react with a substrate to form a product. [ 2 ] [ 17 ] [ 18 ] [ 19 ]


Photosensitizers can be placed into 3 generalized domains based on their molecular structure. These three domains are organometallic photosensitizers, organic photosensitizers, and nanomaterial photosensitizers.


Organometallic photosensitizers contain a metal atom chelated to at least one organic  ligand . The photosensitizing capacities of these molecules result from electronic interactions between the metal and ligand(s).  Popular electron-rich metal centers for these complexes include  Iridium ,  Ruthenium , and  Rhodium . These metals, as well as others, are common metal centers for photosensitizers due to their highly filled  d-orbitals , or high  d-electron  counts, to promote  metal to ligand charge transfer  from pi-electron accepting ligands. This interaction between the metal center and the ligand leads to a large continuum of orbitals within both the  highest occupied molecular orbital  (HOMO) and the  lowest unoccupied molecular orbital  (LUMO) which allows for excited electrons to switch multiplicities via intersystem crossing. [ 20 ]


While many organometallic photosensitizer compounds are made synthetically, there also exists naturally occurring,  light-harvesting  organometallic photosensitizers as well. Some relevant naturally occurring examples of organometallic photosensitizers include  Chlorophyll A  and  Chlorophyll B . [ 20 ] [ 21 ]


Organic photosensitizers are carbon-based molecules which are capable of photosensitizing. The earliest studied photosensitizers were aromatic hydrocarbons which absorbed light in the presence of oxygen to produce reactive oxygen species. [ 22 ]  These organic photosensitizers are made up of highly  conjugated  systems which promote  electron delocalization . Due to their high conjugation, these systems have a smaller gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) as well as a continuum of orbitals within the HOMO and LUMO. The smaller  band gap  and the continuum of orbitals in both the  conduction band  and the  valence band  allow for these materials to enter their triplet state more efficiently, making them better photosensitizers. Some notable organic photosensitizers which have been studied extensively include benzophenones, methylene blue, rose Bengal, flavins, pterins [ 23 ]  and others. [ 24 ]


Colloidal  quantum dots  are nanoscale  semiconductor  materials with highly tunable optical and electronic properties. Quantum dots photosensitize via the same mechanism as organometallic photosensitizers and organic photosensitizers, but their nanoscale properties allow for greater control in distinctive aspects. Some key advantages to the use of quantum dots as photosensitizers includes their small, tunable  band gap  which allows for efficient transitions to the triplet state, and their insolubility in many solvents which allows for easy retrieval from a synthetic reaction mixture. [ 18 ]


Nanorods , similar in size to quantum dots, have tunable optical and electronic properties. Based on their size and material composition, it is possible to tune the maximum absorption peak for nanorods during their synthesis. This control has led to the creation of photosensitizing nanorods. [ 25 ]


Photodynamic therapy  utilizes Type II photosensitizers to harvest light to degrade  tumors  or cancerous masses. This discovery was first observed back in 1907 by  Hermann von Tappeiner  when he utilized  eosin  to treat skin tumors. [ 11 ]  The photodynamic process is predominantly a noninvasive technique wherein the photosensitizers are put inside a patient so that it may accumulate on the tumor or cancer. When the photosensitizer reaches the tumor or cancer, wavelength specific light is shined on the outside of the patient's affected area. This light (preferably  near infrared  frequency as this allows for the penetration of the skin without acute toxicity) excites the photosensitizer's electrons into the triplet state. Upon excitation, the photosensitizer begins transferring energy to neighboring ground state triplet oxygen to generate excited  singlet oxygen . The resulting excited oxygen species then selectively degrades the tumor or cancerous mass. [ 25 ] [ 26 ] [ 17 ]


In February 2019, medical scientists announced that  iridium  attached to  albumin , creating a photosensitized molecule, can penetrate  cancer cells  and, after being irradiated with light (a process called  photodynamic therapy ), destroy the cancer cells. [ 27 ] [ 28 ]


In 1972, scientists discovered that chlorophyll could absorb sunlight and transfer energy into electrochemical cells. [ 29 ]  This discovery eventually led to the use of photosensitizers as sunlight-harvesting materials in solar cells, mainly through the use of photosensitizer dyes.  Dye Sensitized Solar cells  utilize these photosensitizer dyes to absorb photons from  solar light  and transfer energy rich electrons to the neighboring  semiconductor  material to generate electric energy output. These dyes act as  dopants  to semiconductor surfaces which allows for the transfer of light energy from the photosensitizer to electronic energy within the semiconductor. These photosensitizers are not limited to dyes. They may take the form of any photosensitizing structure, dependent on the semiconductor material to which they are attached. [ 16 ] [ 14 ] [ 30 ] [ 31 ]


Via the absorption of light, photosensitizers can utilize triplet state transfer to reduce small molecules, such as water, to generate Hydrogen gas. As of right now, photosensitizers have generated hydrogen gas by splitting water molecules at a small, laboratory scale. [ 32 ] [ 33 ]


In the early 20th century, chemists observed that various aromatic hydrocarbons in the presence of oxygen could absorb wavelength specific light to generate a peroxide species. [ 12 ]  This discovery of oxygen's reduction by a photosensitizer led to chemists studying photosensitizers as  photoredox catalysts  for their roles in the catalysis of  pericyclic reactions  and other  reduction  and  oxidation  reactions. Photosensitizers in synthetic chemistry allow for the manipulation of electronic transitions within molecules through an externally applied light source. These photosensitizers used in redox chemistry may be organic, organometallic, or nanomaterials depending on the physical and spectral properties required for the reaction. [ 16 ] [ 24 ]


Photosensitizers that are readily incorporated into the external tissues can increase the rate at which reactive oxygen species are generated upon exposure to UV light (such as UV-containing sunlight). Some photosensitizing agents, such as St. John's Wort, appear to increase the incidence of inflammatory skin conditions in animals and have been observed to slightly reduce the minimum tanning dose in humans. [ 34 ] [ 35 ]


Some examples of photosensitizing medications (both investigatory and approved for human use) are:


A  Ramsden emulsion , sometimes named  Pickering emulsion , is an  emulsion  that is stabilized by solid particles (for example  colloidal   silica ) which adsorb onto the  interface  between the water and oil  phases . Typically, the emulsions are either water-in-oil or oil-in-water emulsions, but other more complex systems such as water-in-water, oil-in-oil, water-in-oil-in-water, and oil-in-water-in-oil also do exist. Pickering emulsions were named after  S.U. Pickering , who described the phenomenon in 1907, although the effect was first recognized by  Walter Ramsden  in 1903. [ 1 ] [ 2 ]


If oil and water are mixed and small oil droplets are formed and dispersed throughout the water (oil-in-water emulsion), eventually the droplets will  coalesce  to decrease the amount of energy in the system. However, if solid particles are added to the mixture, they will bind to the surface of the interface and prevent the droplets from coalescing, making the emulsion more stable.


Particle properties such as  hydrophobicity , shape, and size, as well as the  electrolyte  concentration of the continuous phase and the volume ratio of the two phases can have an effect on the stability of the emulsion. The particle’s  contact angle  to the surface of the droplet is a characteristic of the hydrophobicity of the particle. If the contact angle of the particle to the interface is low, the particle will be mostly  wetted  by the droplet and therefore will not be likely to prevent coalescence of the droplets. Particles that are partially hydrophobic are better stabilizers because they are partially wettable by both liquids and therefore bind better to the surface of the droplets. The optimal contact angle for a stable emulsion is achieved when the particle is equally wetted by the two phases (i.e. 90° contact angle). The stabilization energy is given by


where r is the particle radius,

 γ

 O
 W

 {\displaystyle \gamma _{OW}}

  is the interfacial tension, and

 θ

 O
 W

 {\displaystyle \theta _{OW}}

  is the contact angle of the particle with the interface.


When the contact angle is approximately 90°, the energy required to stabilize the system is at its minimum. [ 3 ]
Generally, the phase that preferentially wets the particle will be the continuous phase in the emulsion system. The most common type of Ramsden emulsions are oil-in-water emulsions due to the hydrophilicity of most organic particles.


One example of a Ramsden-stabilized emulsion is homogenized milk. The milk protein ( casein ) units are adsorbed at the surface of the milk fat globules and act as  surfactants . The casein replaces the milkfat globule membrane, which is damaged during homogenization. Other examples of emulsions where Ramsden particles may be the stabilizing species are for example detergents, low-fat chocolates, mayonnaises and margarines.


Ramsden emulsions have gained increased attention and research interest during the last 20 years when the use of traditional  surfactants  was questioned due to environmental, health and cost issues. Synthetic  nanoparticles  as Ramsden emulsion stabilizers with well-defined sizes and compositions have been the primarily particles of interest until recently when also natural organic particles have gained increased attention. They are believed to have advantages such as cost-efficiency and degradability, and are issued from renewable resources. [ 4 ]
Pickering emulsions find applications for  enhanced oil recovery [ 5 ]  or  water remediation . [ 6 ]  Certain Pickering emulsions remain stable even under gastric conditions and show an extraordinary resistance against gastric  lipolysis , [ 7 ]  facilitating their use for controlled lipid digestion and satiation [ 8 ]  or oral delivery systems. [ 9 ]


Additionally, it has been demonstrated that the stability of the Ramsden emulsions can be improved by the use of amphiphilic " Janus particles ", namely particles that have one hydrophobic and one hydrophilic side, due to the higher adsorption energy of the particles at the liquid-liquid interface. [ 10 ]  This is evident when observing  emulsion stabilization using polyelectrolytes .


It is also possible to use  latex  particles for Ramsden stabilization and then fuse these particles to form a permeable shell or capsule, called a colloidosome. [ 11 ]  Moreover, Ramsden emulsion droplets are also suitable templates for  micro-encapsulation  and the formation of closed, non-permeable capsules. [ 12 ]  This form of encapsulation can also be applied to water-in-water emulsions (dispersions of phase-separated aqueous polymer solutions), and can also be reversible. [ 13 ]
Pickering-stabilized microbubbles may have applications as ultrasound  contrast agents . [ 14 ] [ 15 ]


Pill-splitting  refers to the practice of splitting a  tablet  or  pill  to provide a lower dose of the active ingredient, or to obtain multiple smaller doses, either to reduce cost or because the pills available provide a larger dose than required. Many pills that are suitable for splitting ( aspirin  tablets for instance) come pre-scored so that they may easily be halved.


The practice is also referred to as tablet scoring. [ 1 ]


It is unsafe to split some  prescription medications . [ 2 ]


A pill-splitter is a simple and inexpensive device to split medicinal pills or  tablets , comprising some means of holding the tablet in place, a blade, and usually a compartment in which to store the unused part. The tablet is positioned, and the blade pressed down to split it. With care it is often possible to cut a tablet into  quarters . Also available as consumer items are  multiple pill splitters , which cut numerous round or oblong pills in one operation.


A  drug manufacturer  may score pills with a  groove  to both indicate that a pill may be split and to aid the practice of splitting pills. When manufacturers do create grooves in pills, the groove must be consistent for consumers to be able to use them effectively. Many manufacturers choose to not use grooves. The United States government  Center for Drug Evaluation and Research  makes the following recommendations for manufacturers when scoring pills with grooves: [ 3 ]


In the U.S. "uniformity of dosage units" is defined by the  United States Pharmacopeia  (USP), which describes itself as "the official public standards-setting authority for all prescription and over-the-counter medicines, dietary supplements, and other healthcare products manufactured and sold in the United States." [ 4 ]  More than 140 countries develop or rely upon US pharmaceutical standards according to the USP.


The USP standard for dosage uniformity expresses statistical criteria in the complex language of  sampling protocols .  The pharmaceutical dosage literature sometimes boils this down as requiring a  standard deviation  in dosage weight of less than 6%, which roughly corresponds to the weaker rule-of-thumb offered for public consumption that the vast majority of dosage units should be within 15% of the dosage target.  "Dosage unit" is a technical term which covers oral medications (tablets, pills, capsules), as well as non-oral delivery methods. [ 5 ]


A 2002 study of pill-splitting as conducted in four American long-term care facilities determined that 15 of the 22 dispensed prescriptions evaluated (68%) had fragment weight variance in excess of USP standards. [ 6 ]


Pill-splitting can be used to save money on pharmaceutical costs, as many prescription pharmaceuticals are sold at prices less than proportional to the dose.  For example, a 10 mg tablet of a drug might be sold for the same or nearly the same price as a 5 mg tablet. Splitting 10 mg tablets allows the patient to purchase half the number of tablets at a lower price than the same weight of 5 mg tablets.


Both specialist and generalist physicians are not sufficiently aware of and do not communicate with patients about the cost to them of medication. [ 7 ]


Randall Stafford of the  Stanford School of Medicine  published a study in 2002 of common prescription medications in the United States in which he evaluates pill splitting for "potential cost savings and clinical appropriateness".  The study identifies eleven prescription medications that satisfied the study criteria, based on the American pharmaceutical cost structure, pill formulation, and dosages of the time. [ 8 ]   Most of the medications listed in the table from the psychiatric drug class are  antidepressants .


Not all tablets split equally well.  In a 2002 study,  Paxil ,  Zestril  and  Zoloft  split cleanly with 0% rejects.   Glucophage  was described as a hard tablet, requiring significant force, causing tablet halves to fly.   Glyburide  exhibited very poor splitting with many splitting into multiple pieces.   Hydrodiuril  and  Oretic  crumbled.   Lipitor  did not split cleanly, and the coating peeled.  The diamond shaped  Viagra  tablets made location of the midline difficult.  The worst result reported was Oretic 25 mg in which 60% of tablets failed to split to within 15% of target weight. [ 9 ] [ 10 ]


Some drugs have a few different uses, and are usually sold in different packages and different doses for different applications. The price for some applications may be very different from that for other purposes. [ citation needed ]  One example is  Minoxidil , which is well known as a hair-growth stimulant; the same drug under the name  Loniten  is used for blood pressure control in much larger doses at a much lower price per unit weight. [ citation needed ]


The  Food and Drug Administration  (FDA) has called pill splitting "risky". [ 11 ]  At the same time, the FDA approves the manufacture of pills which are intended to be split. [ 11 ]


Splitting pills may result in uneven splitting and creating pieces which will not deliver accurate dosage. [ 11 ]  Pills which are split might not be correctly halved, making the cut pieces unequal in size. [ 11 ]  Some pills are difficult to split. [ 11 ]  Some pills (particularly some  time release drugs ) [ 12 ]  are unsafe to split, and there could be mistakes in identifying when pills should not be split. [ 11 ]


In a  California  court filing dated April 2001,  Trial Lawyers for Public Justice  (TLPJ) brought a class-action lawsuit against  Kaiser Permanente  ( Timmis v. Kaiser Permanente ) on the grounds that "Kaiser's mandatory pill-splitting policy endangers patients' health solely to enhance the HMO's profits" in violation of the  California Unfair Competition Law  (UCL) and the  California Consumer Legal Remedies Act  (CLRA). [ 13 ] [ 14 ]  In December 2004, the  California Court of Appeal  affirmed the trial court ruling that Kaiser's policy did not violate UCL or CLRA, noting the suit had failed to present evidence that the policy was unsafe. [ 15 ]


Polystyrene  is a synthetic hydrocarbon polymer that is widely adaptive and can be used for a variety of purposes in drug delivery. These methods include  polystyrene  microspheres, nanoparticles, and solid foams. In the biomedical engineering field, these methods assist researchers in drug delivery, diagnostics, and imaging strategies. [ 1 ] [ 2 ]


A common group of medication that utilizes a combination of polystyrene and sulfonate functional groups are  polystyrene sulfonates . [ 3 ]  This medication is primarily used to treat  hyperkalemia , a condition that results from an increased blood potassium level. [ 3 ]   FDA  approved equivalents of polystyrene sulfonates are KIONEX, KALEXATE, and SPS. While these are the only current FDA approved drug that utilizes polystyrene, polystyrene sees a number of applications in other pharmacological contexts with nanoparticles and microspheres.


Polystyrene integrated solid foams are not commonly used in biomedical applications but have shown promise as a new drug delivery vehicle. The manipulation of the porous foam networks is a fundamental component in solid foam dosing – affecting variables such as dissolution,  adsorption , and drug diffusion. [ 4 ]  Solid foam structures are particularly attractive due to the predictability in drug release profiles through the highly tunable porosity and high surface area of these foams. [ 4 ]


The process of creating these structures is typically a hassle, requiring multiple step processes in order to synthesis a foam of desired properties. [ 4 ]  However, polystyrene solid foams have been created through simpler methods such as  extrusion  from a blowing agent or polystyrene bead expansion. [ 4 ]  While these methods are typically utilized for insulation or similar industry uses, this production method has also seen use in drug delivery applications [5]. Polystyrene solid foams can also be produced through emulsions. [ 4 ]  An  emulsion  can be created through the combination of two immiscible liquids. [ 4 ]  While many methods are used to create emulsion, Canal et al. used a unique method known as phase inversion temperature (PIT). [ 4 ]  PIT utilizes phase transitions to produce highly concentrated amounts of emulsion quickly. [ 4 ]  Through changes in temperature, solubility, and low interfacial tension, PIT is able to efficiently promote emulsion. [ 4 ]  The porosity of these solid foams is able to be fine-tuned, showing promise for osteogenic and therapeutic applications. [ 4 ]  For example, proposed osteogenic applications include the promotion of bone integration. [ 4 ]  The study conducted by Canal et al., utilized polystyrene solid foams as a drug delivery method to evaluate the drug release profile of  ketoprofen . [ 4 ]  Researchers have stated that understanding the release profile for various drugs with polystyrene solid foams could significantly improve treatment outcomes for many disease states.


Nanoparticles  have been used in drug delivery for applications such as diagnosis and treatment of diseases, with polymeric nanoparticles gaining significant traction as a carrier of drugs or  biomolecules  over the last few decades. [ 5 ] [ 6 ] [ 7 ]  These structures are extremely small, having a diameter < 100 nm. [ 6 ]  The high surface to volume ratio allows nanoparticles to display properties that are different than their bulk material in biological systems. [ 7 ]  These properties have been the sole reason of their use in physiological environments. [ 7 ]  While the structure of nanoparticles is straightforward, the efficacy of nanoparticles is affected by variables such as size and surface modifications which determines their overall biocompatibility and biological interaction. [ 7 ]


Polystyrene nanoparticles are the model nanoparticle used for drug delivery applications because they are easy to synthesize in varying sizes. Size is an important factor in cellular uptake rates, which is important for specific pathways such as the endocytic pathway. In a study conducted by Rejman et al., researchers were able to show that polystyrene nanoparticles with diameters of 50 nm and 100 nm were internalized faster than nanoparticles with diameters of 200 nm and 500 nm. [ 2 ] [ 8 ]  Internalization is vital in understanding the impact the designed nanoparticles are having on the target cells. [ 2 ]  Nanoparticle internalization depends on a couple of key factors such as nanoparticle size, cell type, and time. [ 2 ]  Nanoparticles of larger size are typically internalized through processes such as  phagocytosis  or  micropinocytosis . [ 2 ]  Smaller nanoparticles are typically internalized through processes such as macro-pinocytosis, phagocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin-and caveolae-independent pathways. [ 2 ]  The diversity in pathways is one of the greatest challenges with utilizing these nanoparticles since a case-by-case approach is typically required to maximize the entry pathways. [ 2 ]  To measure nanoparticle internalization, techniques such as fluorescence activated cell sorting/scanning (FACS), inductively coupled plasma (ICP) mass spectroscopy, confocal laser scanning microscopy (CLSM), and imaging flow cytometry (IFC) are utilized, each offering their own advantages and disadvantages. [ 2 ]


The main advantage of polystyrene nanoparticles is their biocompatibility, which allows them to be used broadly for biomedical devices and the study of bio-nano interactions. [ 6 ] [ 7 ]  Furthermore, their ability to not degrade in cellular environments proves to be an asset in biomedical applications. [ 7 ]  A unique property of polystyrene nanoparticles, like some other polymers, is their ability to fuse with proteins. [ 6 ]  When proteins bind to the surface of the nanoparticle, a protein corona is formed. [ 6 ]  A protein corona encapsulates the identity of the nanoparticle, and the properties of the corona can be manipulated based on the physical properties of the nanoparticle. [ 6 ]  The corona can be defined as “soft” or “hard” depending on bonding strength and surface-bound protein exchange rate. [ 6 ]  As such, a soft protein corona is defined by nanoparticles that are loosely bound and proteins that are easily exchangeable. [ 6 ]  In contrast, a hard protein corona has nanoparticles that are tightly bound and proteins that are not as easily exchangeable. [ 6 ]  These kinetics are vital in understanding how nanoparticles will respond in biological fluid. [ 6 ] [ 9 ]  The hardness of the protein corona plays a role in the Vroman effect, a principle that describes how proteins with higher affinities replace proteins of lower affinity [8], [11]. The Vroman effect is influenced by protein concentration relative to the surface area and diffusion coefficients. [ 6 ] [ 9 ]  Overall, this affects the protein surface binding affinity. For example, Ehrenburg et al. have shown that fibrinogen presence rapidly declines with polystyrene nanoparticles containing functional groups, such as COOH and CH 3 . [ 10 ]  This allows a protein such as albumin, with a lower affinity, to adsorb and become replaced by fibrinogen. [ 10 ]  Overall, polymeric nanoparticles that can fuse with proteins have a significant advantage over other polymeric nanoparticles due to this versatility in biological interaction.


Certain properties of polystyrene nanoparticles can be modified depending on the scenario. For instance, the surface of polystyrene nanoparticles can be manipulated by surface oxidation, which creates a surface that is highly receptive with cell cultures. These surface-level modifications also express a lower polydispersity index and can create stable colloids in biological liquid. [ 11 ]  Similarly, the surface of these nanoparticles can be treated with  ethylene oxide  or  UV irradiation  for sterilization purposes. [ 7 ]  Due to the emphasis on biocompatibility, Loos et al. have utilized polystyrene nanoparticles as a model to analyze how different surface properties affect biomedical variables. [ 7 ]  Overall, it was determined that a strong understanding of surface properties is vital to manipulate parameters such as  pharmacokinetics , biocompatibility, and tissue and cell affinity. [ 7 ]   In a study conducted by Lundqvist et al., the protein corona was studied with three surface modified polystyrene (plain, carboxyl-modified, and amine-modified) nanoparticles of two different sizes (50 nm and 100 nm). [ 12 ]  This study ultimately showed that surface corona properties are also affected by size and surface composition. [ 12 ]


Polystyrene nanoparticles have been used in various applications such as cancer treatment. [ 1 ]  The primary issue associated with treating cancer is that many chemotherapies suffer from poor penetration into tumor cells. [ 1 ]  In a study conducted by Larina et al., researchers utilized polystyrene nanoparticles in conjunction with ultrasound radiation to influence tumor regression. [ 1 ]  They proposed a method of utilizing ultrasound-induced cavitation to enhance drug delivery to cancer cells. [ 1 ]  Nanoparticles have typically been used in these applications because they are able to accumulate in these tumor sites actively or passively. [ 1 ]  For this application, since cavitation is an important factor, polystyrene nanoparticles were used since their presence allows cavitation to occur at lower pressure intensities. [ 1 ]  Within mice models, their study found that ultrasound irradiation and polystyrene nanoparticles with a combination of 5-FU injections showed strong levels of tumor inhibition and total tumor regression. [ 1 ]


The effect of polystyrene nanoparticles on various cell lines have also been researched. [ 13 ]  Application with human gastric adenocarcinoma cell (AGS) lines has been studied due to these cells being the first line of contact with nanoparticles from ingestion. [ 13 ]  The goal of the study by Forte et al. was a further understanding of nanoparticle interaction with biological systems by studying the kinetic uptake of polystyrene nanoparticle uptake by AGS cells. [ 13 ]  Just as previous studies have shown, it was concluded that the primary factors that influence drug delivery strategies are the size and concentration of these nanoparticles. [ 13 ]


Polystyrene nanoparticle composites have also been the focus of literature due to their adaptability. Composites are useful since the properties for the constituent materials can be combined in a way that is unlike the original components. [ 14 ]  This is extremely relevant in drug delivery applications to fine tune specific parameters case-by-case. In a study conducted by Lim et al., a composite of mono-disperse Fe 3 O 4  and polystyrene nanoparticles were utilized for cardiac myocyte treatment via magnetic targeting. [ 14 ]  Other polystyrene composites have been created with silica nanoparticles. [ citation needed ]  These materials are attractive for a number of reasons such as having low toxicity, being able to control its particle size, strong chemical and thermal stability, biocompatibility, and degradability in physiological environments. [ citation needed ]  Since many of these properties are already present in polystyrene nanoparticles (i.e.,  biocompatibility  and particle size), these structures only enhance its effect in biological environments. [ citation needed ]  As a result, composites such as these have seen increased use a mode of drug delivery.


Microspheres  (or microparticles) are a group of small spherical particles that typically have a diameter ranging from 1 μm to 1000 μm. [ citation needed ]  While microspheres can be created through natural or synthetic purposes, synthetic polymer microspheres offer useful advantages over other options. [ citation needed ]  The most common types of polymeric microspheres are  polyethylene  and polystyrene; however, polystyrene microspheres are especially useful in biomedical applications because they are able to actively facilitate cell sorting and  immunoprecipitation . [ citation needed ]  This results in proteins and ligands adsorbing readily, similar to polystyrene nanoparticles. Polystyrene microparticles are also  hydrophobic  meaning that they will not swell when exposed to a biological environment. [ citation needed ]  Microspheres are applicable with a myriad of drug delivery applications (e.g.,  ophthalmic , gene, intra-tumoral, local, oral, nasal, gastrointestinal, peroral, vaginal, transdermal, and colonic drug delivery). [ citation needed ]  Polystyrene microspheres have also seen use in magnetic and radiolabeled microspheres. [ 15 ]  Similarly, model microspheres such as carboxylated polystyrene microspheres have been used for many studies due to high ligand conjugation through carbodiimide chemistry. [ 15 ]


The way that microspheres are prepared can influence their physical properties. Preparation methods such as  precipitation polymerization , seed polymerization, microemulsion, and dispersion polymerization have been used in the past to create polystyrene microspheres. [ 16 ]  Precipitation polymerization is a robust method of polymer synthesis where a monomer and initiator are dissolved in a solvent. [ 16 ]  This method is advantageous due to low viscosities, clean surfaces, low solid content, and irregular geometries, factors which are beneficial in physiological environments. [ 16 ]  Seed polymerization is a preparation method used to create core-shell emulsions. [ 16 ]  These structures have good stability and narrow particle size distribution, however, due to a long and complex preparation process there is a high likelihood of monomers becoming embedded inside the particles. [ 16 ]  Microemulsions are a method of creating emulsions through an emulsifier. [ 16 ]  By creating particles with microbubbles, this method can create particles that have similar particle size and stability. [ 16 ]  Dispersion polymerization is a method of creating particles with similar size with the advantage of being easy to perform and operate. [ 16 ]  With this method, particle size can easily be modified by manipulating the concentrations of stabilizer, co-monomer, and water. [ 16 ] [ 17 ]  Due to these reasons, dispersion polymerization has become one of the primary methods of polystyrene microsphere synthesis. [ 16 ]  Each of these methods offer their own advantages and disadvantages and are chosen for microsphere synthesis accordingly.


Polystyrene microspheres have previously been used for  serological tests  (i.e.,  rheumatoid arthritis ,  disseminated lupus erythematous , and  pregnancy tests ). [ 18 ]  Saravanan et al. have shown that polystyrene microspheres can be used for controlled drug delivery applications with  ibuprofen . [ 18 ]  One of the biggest limitations associated with drug delivery is that intravenously injected drug carriers (e.g., microspheres and  liposomes ) become trapped by mononuclear phagocyte system (MGS) cells. [ 19 ]  This limitation is important to overcome for the progression of treatment outcomes for diseases such as  AIDS  and  tuberculosis  which primarily rely on the macrophage response system. [ 19 ]  A study by Makino et al. delved into the required size and surface modifications required for alveolar macrophages to uptake polystyrene microspheres. [ 19 ]  It was shown that microspheres with a softer surface were more accessible to alveolar macrophages. [ 19 ]  Moreover, primary amine groups were also shown to be more effective over carboxyl groups. [ 19 ]  As a result, polystyrene microspheres have seen increased use a mode of drug delivery.


One of the most important factors to consider is the toxicity of the polystyrene particles. Many  in vitro  studies have been conducted to understand how these structures can affect reactive oxygen species generation and cell viability. [ 6 ] [ 20 ]  Overall, these studies showed that polystyrene nanoparticles did not affect cell viability. [ 6 ] [ 20 ]


Similarly, it is important to consider polystyrene toxicity in human models. The use of polystyrene has been under scrutiny by various international and local agencies due to the effects of polystyrene on the environment. As a result, there has always been a cause for concern for how polystyrene can affect human health. The  Environmental Protection Agency (EPA)  and studies conducted by Mutti et al. claim that the chronic toxicity of styrene is 300ppm (1,000 μg/m 3 ). [ 6 ] [ 21 ]  Within the polymer industry, these levels typically don't go over 20ppm. [ 6 ] [ 21 ]  Furthermore, the FDA reports that the admissible daily intake (ADI) is 90,000 μg/person/day. [ 6 ]


Reduction-sensitive nanoparticles  (RSNP) consist of  nanocarriers  that are chemically responsive to  reduction . Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment, such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.


Nanoparticles  are small in size with maximized surface area and have an enhanced level of solubility; these elements result in an improved bioavailability. [ 1 ] [ 2 ]  Reduction-Sensitive Nanoparticles are nanoparticles that are responsive to reduction signaling environments. Redox-Sensitive Nanoparticles can be responsive to signaling through a reduction activation or an oxidative activation. Therefore, degradation of chemical bonds can be either activated through  oxidants  or  reductants  in the localized area. The cleavage/degradation of chemical bonds will enable the drugs loaded within the nanoparticle to be released into the body. Depending on the activation mechanism, Redox-Sensitive Nanoparticles can be associated with Reduction-Sensitive Nanoparticles if the chemical activation method is through reduction.


Nanoparticle Drug Loading is dependent on the mass ratio of the drug being loaded and the drug-loaded nanoparticle. [ 3 ]  Variations necessary to consider are the pore volume size, the surface, shape, and charge of the nanoparticle. The mode of drug loading will depend on the type of drug being administered, which will vary depending on the illness that is treated.


One of the limitations of nanoparticles for drug delivery is the insufficient or slow release of drugs. The rate of release is a critical element to identify how slowed drug release could limit the proper concentration of treatment. If the drug is not administered in concentrations high enough it could result in undertreatment of tumor cells with little to no effect. Concentration thresholds must be met to initiate cell death amongst tumor cells. However, the uncontrolled release of treatment could also permit adverse side effects. RSNPs have improved rates of drug release which improves the medication concentrations that can be administered to a specific area.


RSNPs consist of reduction or redox-sensitive bonds. After administration in the body, the RSNP will eventually come into contact with the  tumor microenvironment  (TME). Nanoparticles can be synthesized to activate when exposed to selective characteristics of the tumor microenvironments. TMEs depict unique characteristics that create a differing microenvironment in comparison to healthy tissue. Thus, nanoparticles can be designed to react to the unique elements of TMEs such as the formation of a reducing environment. The reducing abilities of the TMEs are due to the expression of reducing agents. [ 4 ]  RSNPs are formulated to express reduction-sensitive bonds that are cleaved when exposed to reducing agents. After the reduction occurs the degradation of the nanoparticles commences and the loaded drugs begin to release.


The physicochemical characteristics of nanoparticles are inclusive of the size, shape, chemical composition, stability, topography, surface charge, and surface area. [ 5 ]  Deviations of these characteristics can be impacted by the classification of the nanoparticle. For example, the RSNP can be classified as a polymeric, micelle, or lipid-polymeric hybrid. [ 6 ] [ 7 ]  The reduction sensitivity of nanoparticles is reliant on the reduction-responsive chemical structures infused into the nanoparticle. Reduction occurs when the number of electrons increases in a chemical species. Reduction sensitive nanoparticles depict high plasma stability and quick responsiveness/activation. [ 2 ]  The reducing environment of tumor cells is greatly impacted by the oxidation and reduction states of  NADPH /NADP+ and  Glutathione . [ 8 ] [ 9 ]


For the effective application of RSNPs, the physicochemical characteristics of the tumor microenvironment must also be considered. The characteristics depicted by the TME are  tumor hypoxia ,  angiogenesis ,  metabolism ,  acidosis ,  reactive oxygen species  (ROS), etc. [ 4 ]  The elements of the tumor microenvironment can affect the reduction-inducing environment. Tumor cells abnormally regulate  redox  homeostasis leading to differences in the redox balance and increases in ROS levels. Research trends have shown that increased levels of ROS are correlated with high levels of antioxidant activity, such as intracellular GSH. [ 4 ]


Glutathione (GSH) or γ-glutamyl-cysteinyl-glycine is a critical biological reducing agent for drug delivery applications; it creates an effective reducing environment in the  cytosol  and  nucleus  of a cell. [ 8 ] [ 9 ]  Glutathione is an  antioxidant  that is naturally produced in the liver and takes part in tissue building, tissue repair, immune responses, chemical production, and protein production. GSH is also a significant signaler of cell differentiation, proliferation, apoptosis, and ferroptosis. [ 9 ]  Furthermore, the glutathione concentration in the tumor microenvironment is reportedly at least four times higher compared to regular tissue. This is due to the high metabolic needs of tumor cells; for example, the rapid proliferation rates of tumor cells. [ 8 ]


The over-expression of nicotinamide adenine dinucleotide phosphate NADPH can lead to higher ROS levels. NADPH has a lower concentration than GSH in the reducing environment. [ 9 ]  NADPH is an electron donor that exists among all organisms; additionally, the NADPH is used as a source of reduction to drive anabolic reactions and redox balances. The reduction and oxidation states of NADPH/NADP+ will influence the reduced responsiveness of the environment. Cancer cells express a unique NADPH homeostasis due to the adaptive alterations of signaling pathways and metabolic enzymes. [ 10 ]


Redox-Sensitive Nanoparticles with  Disulfide bonds  are commonly observed in medical research. RSNP can consist of disulfide bonds that are cleaved and introduced to a reduction condition. Additionally, the reduction of glutathione results in the formation of sulfhydryl groups. [ 8 ] [ 9 ]  In large concentrations of GSH, the disulfide bonds are capable of being cleaved. Following the activation process, the degradation of the drug carrier results in the drug release. These linkages are commonly used between hydrophilic and hydrophobic segments in copolymers. Moreover, RSNP's hydrophilic shells will degrade in response to the reducing environment. The disulfide bonds are used as linkers and cross-linking agents. Disulfide bonds can be expressed attached to the side chains, the backbone, on the surface, and as linkages between moieties. [ 9 ] [ 11 ]


Disulfide bonds can also act as cross-linking agents in micelles nanoparticles. Micelles lack the structural stability as a nanocarrier for drug delivery. The lack of stability can result in the loss of drugs after administration and before reaching the infected area. This occurrence can potentially cause adverse side effects from the improper release of medication. Disulfide bonds can be used as crosslinked structures to increase the structural stability of micelle nanocarriers. In general, these crosslinks are located in the shell or the core of micelles nanoparticles. [ 9 ] [ 12 ] [ 13 ]


Redox-Sensitive Nanoparticles with  Diselenide  bonds share comparable reduction responsiveness to disulfide bonds. Diselenide consists of two selenium atoms along with an additional element or radical. Diselenide bonds are dynamic covalent bonds that can be exchange between molecules. Diselenide bonds have an estimated bond energy of 172 kJ/mol, and disulfide bonds have estimated bond energy of 268 kJ/mol; the lower bond energy holds a higher potential to design an increased sensitive redox-responsive delivery. [ 9 ]  Diselenide bonds have been observed to be attached to hydrophobic parts of amphiphilic triblocks or hyperbranched copolymers to create micelles. [ 8 ]


Succinimide-thioether linkages express sensitivity to reducing environments and can be cleaved as a result. Succinimide-thioether bonds show slower rates of release in comparison to disulfide bonds; however, succinimide-thioether nanoparticles are still sensitive to the reducing environment and are cleaved by GSH for fast intracellular release. [ 9 ]


Nanoparticles with Trimethyl Benzoquinone have demonstrated responsiveness to reduced environments. The experiments that have been conducted testing TMBQ are limited in observing the full scope of TMBQ nanoparticles in delivery systems. [ 9 ]


The synthesis of reduction sensitive nanoparticles is dependent on the mechanism subtype of the nanoparticle. Additionally, the synthesis can vary within subtype classes depending on how the different reduction sensitive bonds are expressed. The deviations of RSNPs can range from attachments to the backbone, side chains, on the surface, etc. Research has been conducted with reduction sensitivity mechanisms using polymeric, lipid-polymer hybrids, and micelles nanoparticles. The production methods would be dependent on the delivery method design for the nanoparticle. Polymeric nanoparticle synthesis occurs from the addition of electrolyte-saturated or a nonelectrolyte-saturated solution with a water-miscible solvent; additionally, the mixture should be constantly stirred. Lipid micelles are formed by amphiphilic molecules through self-assembly. Lipid-polymer hybrids have multiple synthesis methods which consist of the single-step method, the two-step method, nanoprecipitation, emulsification-solvent evaporation, and a non-conventional two-step method. [ 6 ] [ 7 ] [ 14 ] [ 15 ]


Reduction Sensitive Nanoparticles provide a mode of localized drug delivery by targeting elements of the tumor microenvironment. RSNP has the advantages of high stability when adhering to hydraulic degradation, fast responsiveness to the intracellular reducing environment, and drug release occurs in the cytosol and cell nucleus. Furthermore, drug release in the cytosol and cell nucleus has shown the potential to effectively administer treatment of more potent and poorly soluble anticancer drugs. [ 16 ]  The quick-release of RSNPs has the potential to offer an effective treatment for multidrug-resistant tumors. This addresses an important limitation of nanoparticles. Nanoparticle drug delivery often exhibits slow drug release. The slow release can lead the nanomedicine to be released at low concentrations; moreover, these limited concentrations inhibit the cell death of the tumor cells. Polymeric RSNPs have shown improved solubility, stability, biocompatibility, and decreased drug toxicity; for example, carbohydrate polymers. [ 17 ]


The effectiveness of reduction-sensitive nanoparticles is dependent on the responsiveness of the RSNP throughout the body. The microtumor and inflammatory environments contain higher concentrations of reducing agents in contrast to healthy cells; however, healthy cells still express GSH and NADPH. RSNPs are designed to be receptive to higher concentrations of reducing agents for the ability to distinguish between cancer cells and healthy cells. Furthermore, the other limitations are dependent on other characterizations, such as the type of nanoparticle; For example, micelles nanoparticles' lower levels of physical stability which can lead to drug loss and release in unwanted locations. Additionally, polymeric nanoparticles cannot effectively target the tumor and often undergo drug release too early. [ 8 ]


Reduction Sensitive Nanoparticles are used as nanomedicines for drug delivery. As nanocarriers, RSNP can be loaded with drugs for disease therapeutics. [ 18 ]  This is commonly observed in the use of tumor and cancer treatments. Cancer cells create reducing environments that are used for RSNP activation. RSNPS can also increase the penetration of cancer treatment to the cancer cells. Specific applications include, but are not limited to Breast Cancer, Liver Cancer (hepatoma), Melanoma, Lung Cancer, Malignant Glioma, Ovarian Cancer, Cervical Cancer, Subcutaneous EAT, Pancreatic Cancer, Colon Cancer, Prostate Cancer, etc. [ 2 ] [ 8 ] [ 19 ] [ 20 ] [ 21 ]


The development of RSNP for inflammatory diseases has been explored to a lesser extent. Regardless, in more recent years reduction-sensitive and redox-sensitive nanoparticles have gained more momentum in the realm of inflammatory diseases. Further advances have demonstrated Research has been conducted to evaluate the potential of RSNP as a therapeutic for inflammatory bowel disease. The activation mechanism consisted of pH and redox sensitivity. The outcomes of the experiment demonstrated higher selectivity to the reducing potential; therefore establishing the promising potential of RSNPs for the treatment of inflammatory bowel disease. [ 22 ]  Other studies have demonstrated potential applications as activatable magnetic resonance  contrast agents . These proposed agents would help detect and monitor the treatment of inflammatory diseases by applying redox dysregulation. [ 23 ] [ 24 ] [ 25 ]


A  relative analgesia machine  is used by  dentists  to induce inhalation  sedation  in their patients. It delivers a mixture of  nitrous oxide  ("laughing gas") and  oxygen . A relative analgesia machine is simpler than an  anaesthetic machine , as it does not feature the additional  medical ventilator  and  anaesthetic vaporiser , which are only needed for administration of  general anesthetics . Instead the relative analgesia machine is designed for the light form of  anaesthesia  with nitrous oxide, where the patient is less sensitive to pain but remains fully conscious. [ 1 ]


Reverse smoking  is a kind of  smoking  where the burnt end of a hand rolled tobacco leaf is put in the mouth rather than the unlit end of the cigar. [ 1 ]  It is practiced in some parts of  Andhra Pradesh, India ,  Lusaka, Zambia  and the  Philippines . While conventional smoking is more prevalent among men, [ 2 ]  studies suggest that reverse smoking is a more common among women than men. [ 3 ] [ 4 ]  Reverse smoking is considered to be a risk factor for  oral cancer . [ 5 ]


Reverse smoking may cause a pre-malignant version of  Stomatitis nicotina , [ 6 ]  also called "smoker's palate", characterized by melanin depigmentation and epithelial thinning. [ 7 ] [ 8 ]


This  health -related article is a  stub . You can help Wikipedia by  expanding it .


A  safety syringe  is a  syringe  with a built-in safety mechanism to reduce the risk of  needlestick injuries  to healthcare workers and others. The  needle  on a safety syringe can be detachable or permanently attached. On some models, a  sheath  is placed over the needle, whereas in others the needle retracts into the barrel.  Safety needles [ 1 ]  serve the same functions as safety syringes, but the protective mechanism is a part of the needle rather than the syringe. Legislation requiring safety syringes or equivalents has been introduced in many nations since needlestick injuries and re-use prevention became the focus of governments and safety bodies.


There are many types of safety syringes available on the market. [ 2 ]  Auto Disable (AD) syringes are designed as a single use syringe, with an internal mechanism blocking the barrel once depressed so it cannot be depressed again.  The other type of syringe with a re-use prevention feature is the breaking plunger syringe. An internal mechanism cracks the syringe when the plunger is fully depressed to prevent further use. These syringes are only effectively disabled with a full depression of the plunger; users can avoid activating the re-use prevention feature and re-use the syringe.


The more effective safety syringes have reuse and needlestick prevention features.  A sheath or hood slides over the needle after the injection is completed with a Needlestick Prevention Syringe, which also has a re-use prevention feature (either an auto disable mechanism or breaking plunger).  Retractable syringes use either manual or spring-loaded retraction to withdraw the needle into the barrel of the syringe.  Some brands of spring-loaded syringes can have a splatter effect, where blood and fluids are sprayed off the  cannula  from the force of the retraction.  Manual retraction syringes are generally easier to depress because there is no resistance from a spring.


Traditional glass syringes can be re-used once  disinfected . Plastic body syringes have become more popular in recent years because they are disposable. Unfortunately, improper disposal methods and re-use are responsible for transferring  blood borne diseases .


Of the 55 cases documented by the  CDC  of (non- sex work ) occupational transmission of  HIV , 90% were from contaminated needles that pierced the skin. [ 3 ]  The direct cost of needlestick injuries was calculated in a recent study to be between $539 and $672 million US dollars. [ clarification needed ] [ 4 ]  That includes only lab tests, treatment, service and "other"; [ clarification needed ]  it does not take into account lost time and wages for employers and individuals.


Two lawyers,  Mike Weiss  and Paul Danzinger, were approached in 1998 by an inventor, Thomas Shaw, who was having trouble selling a safety syringe developed to protect health care workers from accidentally being infected by dirty needles. The problems were due to  monopolistic  actions of a major industry needle maker and hospital group purchasing organizations. The case was settled before trial for $150 million. [ 6 ]  This was portrayed by the 2011 movie  Puncture . [ 7 ]  Shaw's attempts to get his retractable needle accepted by health care facilities were covered in a 2010  Washington Monthly  article. [ 8 ]


• Washington Monthly, Jul/Aug 2010,   "Dirty Medicine"


A  self-microemulsifying drug delivery system  ( SMEDDS ) is a  drug delivery  system that uses a  microemulsion  achieved by chemical rather than mechanical means.  That is, by an intrinsic property of the drug formulation, rather than by special mixing and handling.  It employs the familiar  ouzo effect  displayed by  anethole  in many  anise -flavored  liquors .  Microemulsions have significant potential for use in drug delivery, and SMEDDS (including so-called "U-type" microemulsions) are the best of these systems identified to date. [ 1 ]   SMEDDS are of particular value in increasing the absorption of  lipophilic  drugs taken by mouth.


SMEDDS in research or development include formulations of the drugs  anethole trithione , [ 2 ]   oridonin , [ 3 ] [ 4 ] [ 5 ]   curcumin , [ 6 ]   vinpocetine , [ 7 ] [ 8 ]   tacrolimus , [ 9 ] [ 10 ] [ 11 ]   mitotane ,  berberine hydrochloride , [ 12 ]   nobiletin , [ 13 ]   piroxicam , [ 14 ] [ 15 ]  anti- malaria  drugs  beta-artemether [ 16 ]  and  halofantrine , [ 17 ] [ 18 ]  anti- HIV  drug  UC 781 , [ 19 ] [ 20 ]   nimodipine , [ 21 ] [ 22 ]   exemestane , [ 23 ]  anti- cancer  drugs  9-nitrocamptothecin  (9-NC) [ 24 ]   paclitaxel , [ 25 ] [ 26 ]  and  seocalcitol , [ 27 ] [ 28 ]   alprostadil  ( intraurethral  use), [ 29 ]   probucol , [ 18 ] [ 30 ]   itraconazole , [ 31 ]   fenofibrate , [ 32 ]   acyclovir , [ 33 ]   simvastatin , [ 34 ] [ 35 ]   xibornol , [ 36 ]   silymarin , [ 37 ] [ 38 ]   alpha-asarone , [ 39 ]   enilconazole , [ 19 ]   puerarin  (an  isoflavone  found in  Pueraria lobata ), [ 40 ] [ 41 ] [ 42 ] [ 43 ]   atorvastatin , [ 44 ] [ 45 ] [ 46 ]   heparin , [ 47 ]   carvedilol , [ 48 ]   ketoconazole , [ 49 ]   gentamicin , [ 50 ]   labrasol , [ 51 ]   flurbiprofen , [ 52 ]   celecoxib , [ 53 ]   danazol , [ 54 ]   cyclosporine , [ 55 ]  and  idebenone . [ 56 ]


Actual applications of  Self-microemulsifying drug delivery system'  (SMEDDS) remain rare. The first drug marketed as a SMEDDS was  cyclosporin , and it had significantly improved bioavailability compared with the conventional solution. In the last decade, several SMEDDS loaded with antiviral drugs ( ritonavir ,  saquinavir ) were tested for treatment of HIV infection, but the relative improvement in clinical benefit was not significant. The SMEDDS formulation of  ritonavir  (soft capsules) has been withdrawn in some countries. [ 57 ]


Within the last years SMEDDS were also utilized for the oral administration of biologics. Due to ion pairing with appropriate surfactants  [ 58 ]  these mainly hydrophilic macromolecular drugs can be incorporated in the lipophilic phase of SMEDDS. Provided that the oily droplets being formed in the gut are sufficiently stable towards lipases, [ 59 ]  can permeate the mucus gel layer in sufficient quantities  [ 60 ]  and exhibit permeation enhancing properties  [ 61 ]  the oral bioavailability of various biologics can be strongly improved  [ 62 ]


SMEDDS offer numerous advantages: spontaneous formation, ease of manufacture, thermodynamic stability, and improved solubilization of bioactive materials. [ 1 ]   Improved solubility contributes to faster release rates and greater bioavailability.  For many drugs taken by mouth, faster release rates improve the drug acceptance by consumers. Greater bioavailability means that less drug need be used; this may lower cost, and does lower the stomach irritation and toxicity of drugs taken by mouth.


For oral use, SMEDDS may be formulated as liquids or solids, the solids packaged in capsules or tablets. Limited studies comparing these report that in terms of bioavailability liquid SMEDDS are superior to solid SMEDDS, [ 21 ]  which are superior to conventional tablets. [ 21 ] [ 42 ] [ 47 ]   Liquid SMEDDS have also shown value in injectable (IV and urethral) formulations and in a topical (oral) spray. [ 36 ]


Shampoo  ( / ʃ æ m ˈ p uː / ) is a  hair care  product, typically in the form of a  viscous  liquid, that is formulated to be used for cleaning (scalp)  hair . Less commonly, it is available in solid bar format. (" Dry shampoo " is a separate product.) Shampoo is used by applying it to wet hair, massaging the product in the hair, roots and scalp, and then rinsing it out. Some users may follow a shampooing with the use of  hair conditioner .


Shampoo is typically used to remove the unwanted build-up of  sebum  (natural oils) in the hair without stripping out so much as to make hair unmanageable. Shampoo is generally made by combining a  surfactant , most often  sodium lauryl sulfate  or  sodium laureth sulfate , with a co-surfactant, most often  cocamidopropyl betaine  in water. The  sulfate  ingredient acts as a  surfactant , trapping oils and other contaminants, similarly to  soap .


Shampoos are marketed to people with hair. There are also shampoos intended for animals that may contain  insecticides  or other  medications  to treat skin conditions or  parasite  infestations such as  fleas .


In the  Indian subcontinent , a variety of herbs and their extracts have been used as shampoos since ancient times. The first origin of shampoo came from the  Indus Valley Civilization . A very effective early shampoo was made by boiling  Sapindus  with dried  Indian gooseberry  (amla) and a selection of other herbs, using the strained extract. [ citation needed ]   Sapindus , also known as soapberries or soapnuts, a tropical tree widespread in India, is called  ksuna  (Sanskrit: क्षुण) [ 1 ]  in ancient Indian texts and its fruit pulp contains  saponins  which are a natural surfactant. The extract of soapberries creates a lather which Indian texts called  phenaka  (Sanskrit: फेनक). [ 2 ]  It leaves the hair soft, shiny and manageable. Other products used for hair cleansing were shikakai ( Acacia concinna ),  hibiscus  flowers, [ 3 ] [ 4 ]  ritha ( Sapindus mukorossi ) and arappu ( Albizzia amara ). [ 5 ]   Guru Nanak , the founder and the first  Guru  of  Sikhism , made references to soapberry tree and soap in the 16th century. [ 6 ]


Cleansing the hair and body massage (champu) during one's daily bath was an indulgence of early colonial traders in India. When they returned to Europe, they introduced the newly learned habits, including the hair treatment they called shampoo. [ 7 ]   The word  shampoo  entered the English language from the  Indian subcontinent  during the  colonial era . [ 8 ]  It dated to 1762 and was derived from the  Hindi  word  cā̃pō  ( चाँपो ,  pronounced   [tʃãːpoː] ), [ 9 ] [ 10 ]  itself derived from the  Sanskrit  root  chapati  ( चपति ), which means 'to press, knead, or soothe'. [ 11 ] [ 12 ]


Sake Dean Mahomed , an Indian traveller, surgeon, and entrepreneur, is credited with introducing the practice of  shampoo  or "shampooing" to Britain. In 1814, Mahomed, with his Irish wife Jane Daly, opened the first commercial "shampooing" vapour masseur bath in England, in  Brighton . He described the treatment in a local paper as "The Indian Medicated Vapour Bath (type of Turkish bath), a cure to many diseases and giving full relief when everything fails; particularly Rheumatic and paralytic, gout, stiff joints, old sprains, lame legs, aches and pains in the joints". [ 13 ]  This medical work featured testimonies from his patients, as well as the details of the treatment made him famous. The book acted as a marketing tool for his unique baths in Brighton and capitalised on the early 19th-century trend for seaside spa treatments. [ 14 ]


During the early stages of shampoo in  Europe , English  hair stylists  boiled shaved  soap  in  water  and added  herbs  to give the hair shine and  fragrance . Commercially made shampoo was available from the turn of the 20th century. A 1914 advertisement for Canthrox Shampoo in  American Magazine  showed young women at camp washing their hair with Canthrox in a lake; magazine advertisements in 1914 by  Rexall  featured Harmony Hair Beautifier and Shampoo. [ 15 ]


In 1900, German perfumer and hair-stylist Josef Wilhelm Rausch developed the first liquid hair washing soap and named it "Champooing" in Emmishofen, Switzerland. Later, in 1919, J.W. Rausch developed an antiseptic chamomile shampooing with a pH of 8.5. [ 16 ]


In 1927, liquid shampoo was improved for mass production by German inventor  Hans Schwarzkopf  in Berlin; his name became a shampoo brand sold in Europe.


Originally,  soap  and shampoo were very similar products; both containing the same naturally derived  surfactants , a type of  detergent . Modern shampoo as it is known today was first introduced in the 1930s with  Drene , the first shampoo using synthetic surfactants instead of soap.


Early shampoos used in  Indonesia  were made from the  husk  and  straw  ( merang ) of  rice . The husks and straws were burned into ash, and the ashes (which have  alkaline  properties) are mixed with water to form  lather . The ashes and lather were scrubbed into the hair and rinsed out, leaving the hair clean, but very dry. Afterwards,  coconut oil  was applied to the hair in order to moisturize it. [ 17 ]


Filipinos  have been traditionally using  gugo  before commercial shampoos were sold in stores. The shampoo is obtained by soaking and rubbing the bark of the vine  Gugo  ( Entada phaseoloides ), [ 18 ] [ 19 ]  producing a lather that cleanses the scalp effectively.  Gugo  is also used as an ingredient in  hair tonics . [ 20 ]


Certain  Native American  tribes used extracts from North American plants as hair shampoo; for example the  Costanoans  of present-day coastal  California  used extracts from the  coastal woodfern ,  Dryopteris expansa . [ 21 ]


Before  quinoa  can be eaten the  saponin  must be washed out from the grain prior to cooking. Pre-Columbian  Andean  civilizations used this soapy by-product as a shampoo. [ 22 ]