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**Edited to add that I was only 34 when this happened.**Refusing to go get checked for severe pain in my left ankle.I woke up twelve weeks later in ICU.I had been in a medically induced coma after being found face down in the middle of my living room, barely breathing and running an almost 105 degree fever.My pain had been caused by a blood clot lodged just above the ankle. By the time I was found, the bones in my ankle had developed osteomyelitis. A very rare infection of the bone which causes bone death and a lack of blood flow and oxygen to the affected area.I had been told that the only way to save my life was to amputate. In my sick and fevered delusional state, I had adamantly refused amputation. But the doctors knew it was the only option to save me as the bacteria forming in the dead bones’ marrow was being sent throughout my body, leading to full blown sepsis and my organs were already showing signs of shutting down and despite what measures they took, my fever refused to budge.Out of desperation, the hospital contacted my emergency medical contact -- my brother.Thankfully, several years before, I had had my brother designated as my legal medical power of attorney. I suffer from severe, often unmanageable seizures and often found myself in the hospital post seizure. In order to be properly taken care of, which I often refused in my confused postictal mind, I set my brother up to be able to make important medical decisions for me.My brother asked what options I had regarding salvaging my leg. The doctors told him the scary truth -- if my leg just above the infected bone was not removed asap, the bone death would spread, leaving me with just mere hours to live.Less than 30 minutes later I was in the operating room, having an emergency amputation. During the surgery I experienced Intraoperative cardiac arrest (IOCA). IOCA is a lethal combination of surgery and cardiovascular arrest. IOCA in patients undergoing noncardiac surgery is a rare, but potentially catastrophic event that is associated with high mortality. The immediate cause of most most cardiac arrests is an abnormal heart rhythm. The heart's electrical activity becomes chaotic, and it can't pump blood to the rest of the body. A Diffibulator was used. Diffibulation uses an electrical shock to reset the electrical state of the heart so that it may beat in a controlled rhythm. Surgeries are often ended early cardiac arrest is involved, but given that I would soon die if the surgery wasn't continued -- they powered on.As I suffered from severe, often life threatening, drawn out seizures -- I was placed in a medically induced coma to raise my seizure threshold and decrease or even stop my seizures. This works because most medically induced comas are “created” by giving patients very high doses of a barbiturate. Barbiturates were once the go to drug for seizures, but now as there are many different, less sedating drugs available -- the use of barbiturates in seizure cessation and prevention, has fallen to the wayside.I was also placed in cardiac ICU-- the place where only the most critically ill patients are treated. I was so sick my heart and lungs started to fail and I was placed on an Extracorporeal Membrane Oxygenation (ECMO) machine that took over my heart and lung functions, allowing my heart and lungs to rest. Only roughly 41 percent of people placed on ECMO will survive. It is a last ditch procedure that only the most severe patients are placed on. It is so touch and go from that point, that a nurse (and sometimes a respiratory therapist) who has been especially trained as an ECMO specialist is assigned to one ECMO patient, with their entire shift spent monitoring their patient every minute.The amputation area was refusing to heal properly as my immune system had been compromised. I soon found myself in the operating room again this time getting a Vacuum-assisted closure of a wound -- a type of therapy to help wounds heal. It's also known as wound VAC. During the treatment, the device decreases air pressure on the wound. This can help the wound heal more quickly as the continued vacuum draws out fluid from the wound and increases blood flow to the area.Unfortunately, the wound VAC failed. My family was called into conference with my many doctors and support staff. My wound wasn't healing. In fact, the bone infection had returned and had progressed to the middle of my shin. The vascular surgeon on my case now wanted to “jump" the infection and amputate above the knee. My family knew it was my only option, especially since everyday spent on the ECMO machine in a medically induced coma, my survival rate decreased. So later that same day, I became an above the knee amputee. Another wound VAC was used from the start this time.Also discussed and revealed in the meeting with my medical team and family, was that I had contracted MRSA. I now had three separate strains of staph threatening my survival.MRSA stands for Methicillin-resistant Staphylococcus aureus and refers to a group of bacteria that are genetically distinct from other strains of Staphylococcus aureus (“staph infection"). MRSA is a type of staph infection that has mutated into being extremely resistant to most antibiotics normally used to treat staph.The antibiotics used to treat MRSA are extremely tough on your organs, especially your kidneys, and often requires several weeks of IV antibiotics in the hospital. Now not only was my immune system compromised, most of my right leg amputated, my heart and lungs so weak I was placed on life support, my liver showing elevated enzymes, now my kidneys were being damaged and slowly started to shutdown. A special machine was be added to the ECMO machine to slowly remove fluid and clean the blood. This form of dialysis is referred to as continuous renal replacement therapy (CRRT).As I was unable to eat or drink, I was on continuous liquids with additions like iron and potassium. Due to being on dialysis, my body was being flushed of vital proteins, aminoacids, lipids (vital fats), and other essential nutrients. Even if I was capable of eating and drinking, a lot of dialysis patients have to supplement their diets due to the intense filtering process.My body chemistry was analyzed and I was given TPN. Total parenteral nutrition (TPN) is a method of feeding that bypasses the gastrointestinal tract. Fluids are given into a vein to provide most of the nutrients the body needs. TPN is tailored specifically for each patient based on their chemical, caloric, and nutritional needs. No two persons' TPN will be the same “cocktail".Even with all these medical interventions, my odds of survival were quickly declining with every hour. At one point the doctors suggested to my family that they take this time to prepare themselves for the worst possible outcome. A chaplain and grief counselor were dispatched.Days went on and on. My family and medical team refused to give up on me.Then… ever so slowly, things began to turn around and I was improving!The wound VAC was working and the wound was finally healing. Scan after scan showed no signs of osteomyelitis. My white blood cell count was normalizing. My abnormal liver enzymes were adjusting. I started producing more urine. It was decided that the ECMO could be gradually decreased and the CRRT be removed. My medically induced coma was also decreased until I was no longer considered “in a coma", but rather was heavily sedated. The main reason for being placed in the medically induced coma was to manage my seizure activity so the process was carried out very cautiously.Five days later, I had what is called a “trial off". This means that the ECMO would be turned off and I was closely monitored and tons of labs and scans were done to ensure continued progress. And I passed! A few days later I was back in the operating room getting the huge ECMO tubes surgically placed in the large veins in my groin removed! After the surgery, I was moved from cardiac ICU to the “regular” ICU.For two more days, my sedation was gradually backed off until July 23rd 2018. The day I woke up in ICU. After twelve weeks!I remember being told that I needed to be still and that I wasn't allowed to get up. I was so very confused! I didnt remember the week before I ended up in the hospital until that day in July. I thought people were messing with me when I was told it was the end of July!! I thought it was still the end of April!!When I was told I had had an amputation… I laughed and said “No. I can still wiggle my toes!!”I didnt understand phantom pain and sensation.The nurses finally had to pull back the sheet and point it out.First thing I said?“No! My tattoo is gone!!”After that, I had problems processing all that had happened to me. I inappropriately found the whole situation unbelievable … and FUNNY!!I mean, who wakes up after 12 weeks without a leg all because your ankle hurt??Soon I was moved to a regular unit and started occupational and physical therapy as I was closely monitored for worsening infection or the return of osteomyelitis. I went from heavy IV antibiotics to oral. And soon I was well enough on August 28th 2018 to be moved to a rehab facility to continue my occupational and physical therapies. I finally returned home September 27th 2018.Over FIVE MONTHS since I had noticed pain in my left ankle. If I had only gone to the doctor when it didnt get better…Maybe I'd have all my limbs and an entire summer I'd actually remember…

How Do You Get Infected With HIV?The Human Immunodeficiency Virus (HIV) is not spread easily. You can only get HIV if you get infected blood or sexual fluids into your system. You can't get it from mosquito bites, coughing or sneezing, sharing household items, or swimming in the same pool as someone with HIV.Some people talk about "shared body fluids" being risky for HIV, but no documented cases of HIV have been caused by sweat, saliva or tears. However, even small amounts of blood in your mouth might transmit HIV during kissing or oral sex. Blood can come from flossing your teeth, or from sores caused by gum disease, or by eating very hot or sharp, pointed food.To infect someone, the virus has to get past the body's defenses. These include skin and saliva. If your skin is not broken or cut, it protects you against infection from blood or sexual fluids. Saliva can help kill HIV in your mouth.If HIV-infected blood or sexual fluid gets inside your body, you can get infected. This can happen through an open sore or wound, during sexual activity, or if you share equipment to inject drugs.HIV can also be spread from a mother to her child during pregnancy or delivery. This is called "vertical transmission." A baby can also be infected by drinking an infected woman's breast milk. Fact Sheet 611 has more information on pregnancy.Blood and any body fluid visibly contaminated with blood should be considered capable of transmitting hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Semen and vaginal secretions should also be considered potentially able to transmit these viruses. Similarly, cerebrospinal fluid, amniotic fluid, pleural fluid, synovial fluid, and peritoneal and pericardial fluids carry a significant risk of transmitting these viruses.In contrast, unless blood is visibly present, saliva, sputum, sweat, tears, feces, nasal secretions, urine, and vomitus carry a very low risk of transmission of HCV and HIV. It should be noted that saliva can also carry HBV.Occupational transmission of blood-borne infections may also occur through parenteral, mucous membrane, and non-intact skin exposure. The greatest risk for transdermal transmission is via a skin penetration injury that is fairly deep and sustained with a sharp hollow-bore needle that has visible blood on it that had recently been removed from a blood vessel of a patient with a high viral load.Although many infectious agents may be transmitted by such contact, the most consequential include HBV, HCV, and HIV. (See Pathophysiology and Prognosis.)In addition, skin and soft-tissue infection at the site of the inoculation, through introduction of staphylococcal species, is an issue of concern and must not be neglected. Tetanus prophylaxis is also an important issue of concern. Another important issue is the fact that many medical institutions adopt clinical pathways, algorithms, and plans for management of their own health care personnel but are woefully lacking when faced with the outside individual at significant risk for these diseases from needlesticks, mucous membrane splashes, or sexual encounters. (See Treatment and Medication.)Health care personnel include employees, volunteers, attending clinicians, students, contractors, and any public safety workers whose activities involve contact with patients and their environment such that exposure to blood or other body fluids can occur. Nurses, trainees, and students are at especially high risk for significant morbidity from these exposures.Non–health care personnel may be exposed by way of social interaction, sexual encounters (including sexual assault), trauma scenarios, intentional inoculations consistent with contemporary terrorist activity, or drug abuse. A flow chart for the management of body fluid exposure is shown below.Flowsheet for management of blood/body fluid exposures.Infection riskBody fluid exposures carry a risk of transmitting HIV, HBV, and HCV. The risk of developing HIV after a needlestick injury involving an HIV-infected patient is around 0.3%. Factors that increase the odds of HIV transmission after percutaneous exposure include a deep injury, the presence of visible blood on the instrument causing the exposure, injury via a needle that was placed in a vein or artery of the source patient, and terminal illness in the source patient.Wearing gloves may reduce (>50%) the volume of blood introduced through an injury. (See Prognosis.)Note that the risk of HIV transmission in health care workers from exposure of the mucosa to HIV-infected fluids was extremely low (0.09%) and that no cases of HIV conversion after exposure of intact skin to HIV-contaminated fluids or from bites (unless visible blood was present) were reported.How Can You Protect Yourself and Others?Unless you are 100% sure that you and the people you are with do not have HIV infection, you should take steps to prevent getting infected. People recently infected (within the past 2 or 3 months) are most likely to transmit HIV to others. This is when their viral load is the highest. In general, the risk of transmission is higher with higher viral loads.This fact sheet provides an overview of HIV prevention, and refers you to other fact sheets for more details on specific topics.Sexual ActivityYou can avoid any risk of HIV if you practice abstinence (not having sex). You also won't get infected if your penis, mouth, vagina or rectum doesn't touch anyone else's penis, mouth, vagina, or rectum. Safe activities include kissing, erotic massage, masturbation or hand jobs (mutual masturbation). There are no documented cases of HIV transmission through wet clothing.Having sex in a monogamous (faithful) relationship is safe if:Both of you are uninfected (HIV-negative);You both have sex only with your partner; andNeither one of you gets exposed to HIV through drug use or other activities.Oral sex has a lower risk of infection than anal or vaginal sex, especially if there are no open sores or blood in the mouth. See Fact Sheet 152 for information on the risks of various behaviors.You can reduce the risk of infection with HIV and other sexually transmitted diseases by using barriers like condoms. Traditional condoms go on the penis. The "female" condom goes in the vagina or in the rectum of receptive women or men. For more information on condoms, see Fact Sheet 153.Some chemicals called spermicides can prevent pregnancy but they don't prevent HIV. They might even increase your risk of getting infected if they cause irritation or swelling.For more information on safer sex, see Fact Sheet 151.Drug UseIf you're high on drugs, you might forget to use protection during sex. If you use someone else's equipment (needles, syringes, cookers, cotton or rinse water) you can get infected by tiny amounts of blood. The best way to avoid infection is to not use drugs.If you use drugs, you can prevent infection by not injecting them. If you do inject, don't share equipment. If you must share, clean equipment with bleach and water before every use. Fact Sheet 154 has more details on drug use and HIV prevention.Some communities have started exchange programs that give free, clean syringes to people so they won't need to share.Vertical TransmissionWith no treatment, up to 35% of the babies of HIV-infected women would be born infected. The risk drops to about 4% if a woman takes AZT during pregnancy and delivery, and then her newborn is given AZT. The risk is 2% or less if the mother is taking combination antiretroviral therapy (ART). Caesarean section deliveries probably don't reduce transmission risk if the mother's viral load is below 1000.Babies can get infected if they drink breast milk from an HIV-infected woman. Women with HIV should use baby formulas or breast milk from a woman who is not infected to feed their babies. Fact Sheet 611 has more information on HIV and pregnancy.Contact With BloodHIV is one of many diseases that can be transmitted by blood. Be careful if you are helping someone who is bleeding. If your work exposes you to blood, be sure to protect any cuts or open sores on your skin, as well as your eyes and mouth. Your employer should provide gloves, facemasks and other protective equipment, plus training about how to avoid diseases that are spread by blood.What If I've Been Exposed?If you think you have been exposed to HIV, talk to your health care provider or the public health department, and get tested. For more information on HIV testing, see Fact Sheet 102.If you are sure that you have been exposed, call your health care provider immediately to discuss whether you should start taking antiretroviral drugs (ARVs). This is called "post exposure prophylaxis" or PEP. You would take two or three medications for several weeks. These drugs can decrease the risk of infection, but they have some serious side effects. Fact Sheet 156 has more information on PEP.Treatment as PreventionIn 2011 two large studies showed that the use of antiretroviral medications by people not yet infected with HIV led to significant protection against infection. This is called Pre-exposure Prophylaxis (PrEP, see Fact Sheet 160.) Discuss PrEP with your health care provider.The Bottom LineHIV does not spread easily from person to person. To get infected with HIV, infected blood, sexual fluid, or mother's milk has to get into your body. HIV-infected pregnant women can pass the infection to their new babies.To decrease the risk of spreading HIV:Use condoms during sexual activity;Do not share drug injection equipment;If you are HIV-infected and pregnant, talk with your health care provider about taking ARVs;If you are an HIV-infected woman, don't breast feed any baby; andProtect cuts, open sores, and your eyes and mouth from contact with blood.If you think you've been exposed to HIV, get tested and ask your health care provider about taking ARVs.here are some link’s for referencehttps://www.cdc.gov/hai/pdfs/bbp/exp_to_blood.pdfChapter 5: AIDS Facts and Myths - Questions People Ask - AIDS Videohttps://www.cdc.gov/hai/pdfs/bbp/exp_to_blood.pdf

PLoS ONEPublic Library of ScienceThirdhand Cigarette Smoke: Factors Affecting Exposure and RemediationVasundhra Bahl, Peyton Jacob, III, [...], and Prue TalbotAdditional article informationAssociated DataData Availability StatementAbstractThirdhand smoke (THS) refers to components of secondhand smoke that stick to indoor surfaces and persist in the environment. Little is known about exposure levels and possible remediation measures to reduce potential exposure in contaminated areas. This study deals with the effect of aging on THS components and evaluates possible exposure levels and remediation measures. We investigated the concentration of nicotine, five nicotine related alkaloids, and three tobacco specific nitrosamines (TSNAs) in smoke exposed fabrics. Two different extraction methods were used. Cotton terry cloth and polyester fleece were exposed to smoke in controlled laboratory conditions and aged before extraction. Liquid chromatography-tandem mass spectrometry was used for chemical analysis. Fabrics aged for 19 months after smoke exposure retained significant amounts of THS chemicals. During aqueous extraction, cotton cloth released about 41 times as much nicotine and about 78 times the amount of tobacco specific nitrosamines (TSNAs) as polyester after one hour of aqueous extraction. Concentrations of nicotine and TSNAs in extracts of terry cloth exposed to smoke were used to estimate infant/toddler oral exposure and adult dermal exposure to THS. Nicotine exposure from THS residue can be 6.8 times higher in toddlers and 24 times higher in adults and TSNA exposure can be 16 times higher in toddlers and 56 times higher in adults than what would be inhaled by a passive smoker. In addition to providing exposure estimates, our data could be useful in developing remediation strategies and in framing public health policies for indoor environments with THS.IntroductionThirdhand smoke (THS) consists of residual tobacco smoke that sorbs to indoor surfaces and remains after the majority of the airborne components of the smoke have cleared. THS raises the concentration of nicotine and other smoke constituents in indoor environments occupied by smokers [1], [2]. During aging, the chemicals in THS can desorb back into the air or react to form new chemicals. For example, nicotine reacts with ambient nitrous acid (HONO) to form tobacco specific nitrosamines (TSNAs) [3], [4]. Exposure to THS and remediation of buildings and vehicles contaminated with THS have received little attention in the past and are important, especially in light of recent health-related studies that indicate the potentially hazardous nature of THS [5]–[8]. Because THS affects individuals with unknown or unwanted exposure, it is an issue with public health implications [2].The negative health effects of active smoking and secondhand smoke exposure have been analyzed in vitro, in animals, and studies of human volunteers and populations [9]–[13]. Active smoking and secondhand smoke exposure adversely affect health across all age groups [9], [14], [15]. In contrast, little is known about the level of human exposure to THS and the resulting health effects. THS exposure can occur through the skin, by ingestion, and by inhalation. Infants and small children could be at greater risk than adults because their skin is thinner, their surface to volume ratio is higher, and because they spend more time in contact with THS-contaminated surfaces and where they can mouth THS-contaminated objects. If ingested, the fraction of THS that is soluble in saliva and digestive fluids will be available for intake (passage into the body but not across absorptive barriers) [16]. The extent of intake will depend on the concentration of THS chemicals, the fraction of THS that is in the air and on surfaces, and their solubility in saliva or sweat. The concentration of THS chemicals will vary with the number of cigarettes smoked in the room, the air exchange rate, and the time elapsed since smoking. Therefore, when evaluating exposure, it is important to consider that THS is dynamic and that aging can change the composition of THS over time.Remediation, which is the removal of THS residue from surfaces in indoor environments or the safe containment of THS, is another important aspect of THS contamination that needs study [2], [17]. Methods of remediation will depend upon the level of contamination as well as the type of material. The materials commonly found indoors, such as natural and synthetic fibers, carpets, paper and wall board, each differ in their capacities to adsorb, absorb, bind, and release THS chemicals (unpublished data).As a first step to understanding the persistence of THS in indoor environments, potential human exposures, and options for remediation, we repeatedly exposed cotton and polyester fabrics to cigarette smoke in an experimental chamber, stopped exposure and aged the fabrics for up to 19 months, then measured the concentrations of nicotine, nicotine-related alkaloids and tobacco-specific nitrosamines in extracts of fabrics. We tested chemical concentrations in both organic and aqueous solvent extracts, and then used the resulting data to model exposures that toddlers and adults could receive in environments containing THS.MethodsExposure of fabric to cigarette smoke100% cotton terry cloth, and 100% polyester fleece were purchased at retail and washed three times in a domestic washing machine using an unscented, enzyme-free laundry detergent (Country Save powdered laundry detergent, Arlington, WA) in hot water with two rinses/cycle, and washing again with no detergent. These fabrics were chosen as they are commonly used in household products and in clothing. After line drying, fabrics were hung in a 6 m3 stainless steel chamber at UCSF and exposed to cigarette smoke as described previously in detail [18]. Briefly, smoke generated by an automatic smoking machine (Model TE-10z, Teague Enterprises, Woodland, California, USA) was diluted into conditioned, filtered air, and conducted through a 6 m3 stainless steel smoke aging chamber. The aging chamber contained three vertically staggered baffles and two internal fans to promote mixing. The cloth samples were hung on the baffles. Marlboro Red cigarettes were smoked according to ISO protocol 3308: 2012. Marlboro Red was chosen as it is the best-selling cigarette in the United States and is popular worldwide. Particle concentration at the outlet of the smoke aging chamber was measured using a laser photometer calibrated gravimetrically (Dusttrak II, model 8530, TSI Inc., Shoreview MI). Aerosol flow rates through the chamber were measured using an air velocity transmitter (model 641-b Dwyer Instruments, Michigan City IN). After smoking, air flow was turned off, and the chamber was closed while it still contained detectable levels of smoke. Smoke was generated 0–8 times/month according to the needs of ongoing clinical research between experiments. The time that the cloth sample was in the chamber, the number of hours of smoke, the average particle concentration for each experiment and the air velocity through the chamber were logged. The total particle mass that the fabric was exposed to was calculated as An external file that holds a picture, illustration, etc.Object name is pone.0108258.e001.jpg where a = air velocity in liters/minute, b = hours of smoke, and c = average smoke particle concentration.A sheet of cotton terry cloth and a sheet of polyester fleece were exposed to smoke. The terry cloth was exposed to smoke containing 1329 mgs of particles for 114 hours over 1 year. The polyester fleece was exposed to 1846 mgs of smoke particles for 257 hours over 10 months. Both fabrics were folded and stored in separate polyethylene bags at room temperature in the dark. The terry cloth was stored 8 months and the polyester 1 month prior to shipment. Samples were wrapped in aluminum foil, placed in polyethylene bags and shipped at ambient temperature, overnight, to the Talbot Laboratory at UCR. Upon receipt, samples were transferred to amber glass bottles and stored at room temperature (RT) in the dark.Organic solvent extractionsSamples of fabric were incubated at RT overnight in 50% MeOH/1% HCl then vortexed for 3–5 minutes at RT. Solvent was removed by squeezing the fabric in the vial with a spatula, fibers and dust were removed by centrifugation, and the extract was analyzed as described below.Aqueous extractionsAqueous extracts of THS were prepared in Dulbecco's Modified Eagle Medium (DMEM). Terry cloth and polyester fleece were weighed and cut into very small pieces using scissors. Either 0.05 or 0.125 g of fabric/ml were extracted in DMEM in 15 ml conical tubes on a rotating shaker. The medium was recovered by placing the fabric in a syringe and centrifuging at 4,000 g for 5 minutes The recovered medium was passed through a 0.22 µm filter, aliquoted into 1.5 ml vials, and stored at −80°C.To examine the effect of repeated aqueous extraction on chemical yield, three samples of terry cloth and two samples of polyester were extracted five times, serially at RT with media being replaced every hour for 5 hours. To determine the effect of time and temperature, the terry cloth was extracted under four conditions: RT for 1 hour; RT for 2 hours; 4°C for 1 hour; and 4°C for 2 hours. For extraction at 4°C, tubes were placed in a beaker of ice on a rocker shaker. To examine the effect of aging, extraction was done after storing the terry cloth for 11, 16 and 19 months and the polyester for 11 and 19 months in amber glass jars at RT.Chemical Analysis of THS extracts1 mL extracts of THS were shipped to UCSF on dry ice where they were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) [19], [20]. The method was modified to include NNA in the analysis, by treating the extract with pentafluorophenylhydrazine (PFPH) to convert NNA to the pentafluorophenylhydrazone derivative which enhances sensitivity of detection [21].LC-MS/MSThe samples were analyzed on a Thermo Scientific Vantage LC-MS/MS with an Accela UPLC system using a 3×150 mm 2.6 micron Phenomenex Kinetex PFP column as detailed in [20].Limits of quantificationThe limits of quantitation for each of the chemicals analyzed are as follows: nicotine: 1.02 ng/ml; myosmine: 0.305 ng/ml; 2,3′-bipyridine: 0.914 ng/ml; cotinine: 0.914 ng/ml; N-formylnornicotine: 0.305 ng/ml; nicotelline: 0.030 ng/ml; NNN: 0.030 ng/ml; NNK; 0.0130 ng/ml; NNA 0.010 ng/ml.Statistical analysesThe concentrations of chemicals in aqueous extracts were converted to grams/gram of fabric. Averages of four samples in each group were then calculated using Microsoft Excel. ANOVA (one way analysis of variance) was performed using GraphPad Prism to determine if the chemical concentrations in extracts made under different conditions varied significantly. ANOVA was also used to analyze extracts made from terry cloth after 11, 16 and 19 months of aging. Groups differing significantly (p<0.05) from the 11 month samples were identified using Dunnett's posthoc test. Data were checked to determine if they satisfied the assumptions of ANOVA (normal distribution and homogeneity of variances). T-tests were used to determine if the chemical concentrations in aqueous extracts were different from those in methanol/HCL extracts.ResultsFabrics used for extractionTHS was extracted from 100% cotton terry cloth and 100% polyester fleece. Terry cloth is a loosely knit natural fabric with many thin fibers that provide a large surface area for absorption of chemicals. One surface of polyester has numerous short highly packed fibers while the other is comprised of a large tightly woven mesh of fibers (Fig. 1).Figure 1Figure 1Micrographs of fabrics used for THS extraction.Aqueous and methanol∶HCl solvents extracted THS chemicals from cotton fabricThe concentrations of nicotine and related chemicals in the aqueous extracts of THS from cotton terry cloth after 31 months of aging were similar to those in methanol∶HCl extracts (Figs. 2A, B). Negligible amounts of nicotine and related chemicals were recovered when aqueous extraction was followed by methanol∶HCl extraction. Nicotine (50–60 µg/gram of fabric) was the most abundant of the chemicals analyzed. Myosmine, bipyridine, formylnornicotine and cotinine were present in 1–2 µg/gm of fabric quantities, while the TSNAs and nicotelline were the least abundant (nanogram/gram of fabric) of the chemicals analyzed in THS extracts from terry cloth.Figure 2Figure 2Comparison of chemical concentrations in aqueous and methanol∶HCl extracts of terry cloth and polyester exposed to THS.Extraction of polyester fabric yielded lower concentrations of THS chemicalsThe concentrations of all chemicals tested were lower in extracts of polyester fleece than in extracts of cotton terry cloth (Fig. 2C, D). As an example, in aqueous extracts approximately 40 times less nicotine was extracted from polyester than from terry cloth. For polyester fleece, methanol∶HCl and aqueous extracts had similar concentrations of nicotine and other chemicals. However, when aqueous extraction was followed by methanol∶HCl extraction, higher concentrations of myosmine and 2,3′-bipyridine were obtained than with aqueous extractions alone. All other chemicals were retrieved at lower concentrations in the methanol∶HCl extract that followed the aqueous extraction. This suggests two possibilities: that polyester binds less nicotine, nicotine- related alkaloids and TSNAs than cotton or that these compounds are harder to extract from polyester than from cotton.Serial aqueous extractions from terry cloth and polyesterTo determine if all nine chemicals were removed from terry cloth and polyester during 1 hour of aqueous extraction, the same fabric samples were extracted five times. Each extraction lasted one hour (Fig. 3). All of the chemicals extractable by water were successfully removed from cotton terry cloth during the first hour of extraction. Concentrations of some chemicals (e.g., nicotine, myosmine and nicotelline) were very similar from batch to batch, while others, such as cotinine, NNA, and NNN, varied somewhat in concentration among batches. For polyester, cotinine was found only in the first hour extracts. Nicotine and N-formylnornicotine were found in the first and the second hour extracts.Figure 3Figure 3Iterative aqueous extractions from terry cloth and polyester.One hour of aqueous extraction at RT removes THS chemicals from cotton terry clothThe effects of temperature and time on the concentration of chemicals recovered by aqueous extraction was tested (Fig. 4). Extracts were made at RT and at 4°C for 1 or 2 hours. Chemical concentrations appeared to be similar for each extract. When tested by ANOVA, no significant differences in chemical concentrations were found between extraction conditions. Data for each chemical were therefore combined in Table 1, which also includes the combined data for polyester. These data confirm that 1 hour at RT is sufficient time to achieve the maximum yield of each chemical from cotton terry cloth using aqueous medium and that changing the time or temperature does not improve extraction efficiency. All chemicals were more abundant in extracts of terry cloth than in polyester, and NNN and NNA were not detected in the extracts of polyester.Figure 4Figure 4Concentration of chemicals in aqueous extracts of THS from terry cloth when temperature and time of extraction were varied.Table 1Table 1Chemicals identified in aqueous THS extracts.Effect of aging on the concentrations of THS chemicals in extracts from terry cloth and polyesterIn extracts of terry cloth, nicotine concentrations (105.8, 112.9, and 69.6 µg/gram of fabric) at 11, 16, and 19 months of aging (Fig. 5) were not significantly different when evaluated by ANOVA (p = 0.0595). Extracts of polyester made after 11 and 19 months of aging had very low amounts of nicotine (557 ng/g fabric and 168.8 ng/g fabric) in contrast to terry cloth that aged for similar times (Fig. 5A).Figure 5Figure 5Effect of aging on the concentration of nicotine and its derivatives in aqueous extracts of terry cloth and polyester exposed to THS.Myosmine, N-formylnornicotine, 2,3′-bipyridine, and cotinine were present in extracts of terry cloth at µg/gram of fabric concentrations (Fig. 5B). The concentrations of extractable myosmine (p<0.0001), 2,3′-bipyridine (p<0.0001) and cotinine (p = 0.0001) decreased significantly after 19 months of aging (January 2013). The concentration of N-formylnornicotine decreased significantly (p<0.0001) after 16 months of aging, but did not decrease further by 19 months. For this group of chemicals, the extract of polyester which aged 11 months contained only N-formylnornicotine and cotinine, and these were present in low concentrations compared to the corresponding terry cloth sample (11 months) (Fig. 3B). Extracts of polyester made after 19 months of aging had very low levels of myosmine, 2,3′-bypiridne, N-formylnornicotine and cotinine. All the chemicals in extracts of polyester were present at concentrations less than 1 µg/gram of fabric (Fig. 5B).In extracts of terry cloth, concentrations of nicotelline, NNA, NNK and NNN were in the ng/gram of fabric range (Fig. 5C). Of these chemicals, only nicotelline did not decrease in concentration with aging, supporting its use as a tracer for tobacco smoke particulate matter [19]. The concentration of NNA decreased significantly by 19 months of aging (p = 0.0108). For both NNN and NNK, there was a slight but significant increase in concentration at 16 months of aging (p = 0.0020 and 0.0004 respectively), followed by a significant decrease in NNK (p = 0.0421) at 19 months.In extracts of polyester made after 11 months of aging, nicotelline was detected in very small amounts, but the three TSNAs were absent. After 19 months of aging, very small amounts of NNK were also detected (Fig. 5C). Statistical analysis was not performed for extracts of polyester since the extract prepared after 19 months of aging had only two experiments.DiscussionWhile the concentrations of some extractable THS chemicals in cotton terry cloth and polyester fleece changed during aging, in general THS chemicals remained on these fabrics for over 1.5 years after the last exposure to smoke. Nicotine and its derivatives, including NNK, a known carcinogen, were rapidly extracted from cotton fabric in an aqueous medium that is similar in composition to saliva and sweat and has a physiological pH. This implies that an infant who mouths cloth that has been exposed to cigarette smoke will be exposed to significant amounts of cigarette smoke toxicants. There was a large difference in the quantity of chemicals extracted from cotton cloth and polyester cloth, showing that natural and synthetic fibers have different abilities to bind and release THS chemicals. These observations are important in understanding human exposure to THS, devising strategies for remediation of contaminated environments, and in developing regulatory policies for indoor use of tobacco products.Changes in the concentration of an individual THS chemicals of on a surface depend on multiple processes including sorbtion, desorbtion and chemical reactions. Whether a chemical remains on a surface or rapidly desorbs and is removed by ventilation depends on its volatility and chemical properties. Whether a chemical reacts or remains intact depends on its chemical properties and the availability of other chemicals in the environment. With the exception of nicotelline, the chemicals we analyzed are semivolatile organic compounds, which means they will be present in both the gas phase and solid phase at normal indoor temperatures. For terry cloth, myosmine, 2′,3′;-bipyridine, N-formylnornicotine and cotinine decreased significantly during aging, possibly due to breakdown into other chemicals, volatilization, or conversion reactions with the ambient environment.The increased concentrations of both NNN and NNK at 16 months of aging followed by a decrease at 19 months could be due to formation of fresh TSNAs from settled nicotine before reaching a threshold and starting to decrease due to further conversions. Although NNA concentrations did not change in our extracts, the formation of NNA may have occurred prior to our first extraction, after 11 months of aging. Also, NNA, being an aldehyde, is more reactive than NNN and NNK and could have combined with other chemicals during aging. For polyester, the concentrations of all chemicals in aqueous extracts were very low. The increase in the number of chemicals that were present in the polyester sample that aged 19 months vs. 11 months may be an artifact caused by analyzing chemicals close to their lower limit of quantification (0.01 ng/ml to 1 ng/ml for different chemicals).The difference in the concentrations of chemicals extracted from cotton terry cloth and polyester fleece may be due to their surface chemistry. Our data are in agreement with prior studies showing that polar substances like nicotine and dyes do not bind well to polyester [22], [23]. Cotton, which is made of cellulose, has three free hydroxyl groups/glucose monomer that can form hydrogen bonds with the polar groups on nicotine and its derivatives (Fig. 6) [22], [24], [25]. In contrast, polyester which is a polymer of terepthalic acid and ethylene glycol, is highly oleophilic [26], and its hydrophobicity tends to repel polar compounds. However, it is possible that these THS compounds adsorb more strongly to polyester than to cotton and the DMEM or methanol∶HCl extractions we used are not rigorous enough to fully extract them from polyester. THS contains thousands more chemicals than we analyzed, including many non-polar, non-water soluble chemicals. The interactions of other classes of chemicals with indoor surface materials will need to be characterized in future studies.Figure 6Figure 6Chemical interactions of nicotine and its derivatives with terry cloth through hydrogen bonds.Our data clearly show that fabrics found in indoor environments act as reservoirs for THS smoke chemicals. Although the samples used in this study received relatively light exposure to cigarette smoke, significant amounts of nicotine and related chemicals were extractable from cotton cloth 19 months after smoke exposure had stopped. In studies where smoke is released into a large chamber and allowed to mix with the air, age and interact with surfaces before particle concentrations are measured, the mass of particles emitted by a single cigarette ranges from 7–22 mg, with averages between 8 and 14 mg [27]–[30]. Using an average emission factor of 10 mg per cigarette, the cotton cloth was exposed to the equivalent of 133 cigarettes and the polyester was exposed to the equivalent of 185 cigarettes. These exposures translate to 7–9 days of exposure in a room where 20 cigarettes are smoked per day or 27–37 days of exposure in a room where 5 cigarettes are smoked per day. Exposure in our study occurred in a steel chamber and therefore THS chemicals did not have an opportunity to be removed by ventilation, open doors or open windows. Therefore while our experiment was done under controlled laboratory conditions, it does not exactly duplicate a real world situation. However, the fact we used a low number of cigarettes (approximately 133 for terry cloth) supports the idea that in a real world situation the concentrations of the chemicals studied could be much higher than reported here. For example in a home where one individual smokes a pack a day for one year, the total number of cigarettes consumed would be 7,280 in contrast to approximately 133 used in our study. While the health effects of these chemicals in THS residue are not yet known, it may become desirable or even necessary in the future to remediate property with THS residue before it is rented or sold [2]. Our data demonstrate that nicotine and related compounds, including two carcinogens, can easily be removed from cotton fabrics by standard washing methods.Since indoor surfaces act as reservoirs of THS, toddlers and infants could be exposed to THS chemicals by sucking on household fabrics, and all age groups could be exposed dermally by touching contaminated surfaces. To evaluate the exposure that could be received from cotton fabric containing THS residue, we examined a hypothetical scenario for dermal exposure to an adult. An adult wearing a 500 g cotton outfit containing THS residue from 20 cigarettes will be exposed to about 7,894 µg of nicotine/day and 32.7 µg of TSNAs/day, with a small fraction of this contributing to intake, assuming that the outfit would be washed frequently and could reasonably contain THS from 20 cigarettes before being washed.A more accurate scenario can be developed for ingestion exposure to a toddler, where the intake will be roughly equal to the exposure. The main source of THS exposure to a toddler would be through mouthing fabrics used in toys, drapes and upholstery that are not frequently washed and have long-term accumulation of THS. For terry cloth containing THS from about 133 cigarettes (as used in this study), a 12 kg toddler mouthing and sucking 5 grams of cloth for 1 hour would be exposed to 529 µg of nicotine/day and 2.2 µg of TSNAs/day. Since the exposure and intake are equal, the toddler would receive 44 µg/kg body weight of nicotine and 0.183 µg/kg body weight of TSNAs per day. These intake values for the toddler would be less than those received by an active smoker but higher than respiratory exposure in passive smokers (6.8× higher for nicotine and 16× higher for TSNAs) (Table 2). While information on the effects of pre and postnatal nicotine exposure comes largely from animal models and women on nicotine replacement therapy, data consistently show links between nicotine exposure early in life and subsequent cognitive impairment, attention deficit disorders as well as obesity, hypertension, type-2 diabetes, respiratory dysfunction and impaired fertility [31]–[33]. Although the intake value for TSNAs is much less than doses known to cause tumors in rodent models [34], the above scenarios may underestimate exposure if significant levels of chemicals were lost during the first 11 months of aging or if THS accumulates from more than 133 cigarettes. TSNAs contribute to pancreatic cancer [35]. It will be interesting to determine in future studies if there is a correlation between TSNA exposure during infancy and the recent increase in pancreatic or other types of cancer in adults. Exposure of toddlers to nicotine and TSNAs in THS is therefore a matter of concern and may need regulation.Table 2Table 2Estimated nicotine and TSNAs exposure to a toddler.ConclusionsOur data show that under controlled laboratory conditions fabrics exposed to cigarette smoke retain significant concentrations of THS chemicals long after smoking has ceased. Estimated exposure to and uptake of nicotine and TSNAs from residual THS are above what toddlers would receive by inhaling environmental tobacco smoke. These observations coupled with recent reports linking THS exposure to adverse health effects support the idea that THS residues on indoor surfaces are a public health concern. Since THS chemicals do not spontaneously disappear from indoor surfaces, it may be important to actively remove them to reduce risk from THS exposure. Our data show that nicotine, nicotine-related alkaloids and TSNAs could be readily removed from cotton fabrics by washing, which could become a simple remediation procedure.This study focused on THS that had aged in fabrics that are often used in homes and clothing. Studies are in progress to determine the levels of chemicals in freshly exposed household fabrics, such as carpets, drapes and upholstery, as well as the actual intake and uptake levels of THS chemicals in humans and if these concentrations are high enough to produce harm.AcknowledgmentsWe thank Pura Tech for her help handling the samples.Funding StatementThis work was supported by the California Consortium on Thirdhand Smoke, California Tobacco-Related Disease Research Program (Home | TRDRP) grant 20PT-0184 and California Tobacco-Related Disease Research Program grant 21 ST-011, the National Institute on Drug Abuse P30 DA012393, the National Center for Research Resources S10 RR026437, the National Center for Advancing Translational Sciences, National Institutes of Health (National Institutes of Health (NIH)), through UCSF-CTSI Grant Number UL1 TR000004. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies. VB was supported on a Deans Pre-doctoral Fellowship and a California Tobacco-Related Disease Research Program pre-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Data AvailabilityThe authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.Article informationPLoS One. 2014; 9(10): e108258.Published online 2014 Oct 6. doi: 10.1371/journal.pone.0108258PMCID: PMC4186756PMID: 25286392Vasundhra Bahl, 1 , 2 Peyton Jacob, III, 3 Christopher Havel, 3 Suzaynn F. Schick, 4 and Prue Talbot 1 , *Ruby John Anto, Editor1 Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America,2 Environmental Toxicology Graduate Program, University of California Riverside, Riverside, California, United States of America,3 Department of Clinical Pharmacology, University of California San Francisco, San Francisco, California, United States of America,4 Department of Medicine, Division of Occupational and Environmental Medicine, University of California San Francisco, San Francisco, California, United States of America,Rajiv Gandhi Centre for Biotechnology, India,* E-mail: ude.rcu@toblatCompeting Interests: The authors have declared that no competing interests exist.Conceived and designed the experiments: VB PJ SS PT. Performed the experiments: VB CH SS. Analyzed the data: VB PJ CH SS PT. Contributed reagents/materials/analysis tools: VB PJ SS PT. 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