Vojna akademija Beograd

Suicide is the fourth leading cause of death in young adults worldwide. Given the vulnerability of this population, the aim of our retrospective cohort study was to examine the demographic and clinical profile of 193 young adult emergency ward patients at the Clinic for Emergency and Clinical Toxicology of the National Poison Control Centre (NPCC), Military Medical Academy (MMA) in Belgrade, Serbia who attempted suicide by poisoning in 2020–2023. More than half suffered from a mental disorder, and poisoning mainly involved marketed prescription drugs (most often benzodiazepines). Women attempted suicide by poisoning more often and had a history of previous attempts, while men had more ensuing complications and were older. Current mental disorders and current psychopharmacotherapy positively correlated with the number of suicide attempts by poisoning and with the history of previous poisoning with prescription drugs. The number of suicide attempts by poisoning also correlated positively with self-harm. Our results suggest that the experience of the pandemic has highlighted the need to strengthen mental healthcare. Developing the resilience of young people, establishing help centres, and improving public awareness of this important issue could help reduce the incidence of suicide attempts in young adult population.

The randomized controlled pivotal phase 3 study evaluated efficacy and safety of neoadjuvant complex biologic, Leukocyte Interleukin Injection (LI), administered for 3 consecutive weeks pre-surgery, in treatment naïve resectable locally advanced primary squamous cell carcinoma of oral cavity and soft palate. Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. LI-treated patients received 400 IU (as interleukin-2 equivalent; 200 IU peritumorally, 200 IU perilymphatically) sequentially, daily 5 days/week for 3 weeks before surgery. All subjects were to receive SOC. Post-surgery, patients with low risk for recurrence were to receive radiotherapy, while those with high risk received concurrent chemoradiotherapy. Median follow-up was 56 months. There were 923 ITT (Intent-to-Treat) subjects (380 ITT low-risk and 467 ITT high-risk). Pre-surgery objective early response (45 objective early responders; 5 complete responses [CRs], 40 partial responses [PRs], confirmed by pathology at surgery. LI (+/− CIZ) had 8.5% objective early responders (45/529 ITT) and 16% objective early responders (34/212 ITT low-risk) vs. no reported SOC objective early responders (0/394 ITT). Objective early responders significantly lowered death rate to 22.2% (ITT LI-treated), 12.5% (ITT low-risk LI + CIZ + SOC), while the ITT low-risk SOC death rate was 48.7%. Thus, objective early response impacted overall survival (OS); proportional hazard ratios were 0.348 (95% CI: 0.152–0.801) for ITT low-risk LI-treated, 0.246 (95% CI: 0.077–0.787) for ITT low-risk LI + CIZ + SOC. ITT low-risk LI + CIZ + SOC demonstrated significant OS advantage vs. ITT low-risk SOC (unstratified log-rank p = 0.048; Cox hazard ratio = 0.68; 95% CI: 0.48–0.95, Wald p = 0.024 [controlling for tumor stage, tumor location, and geographic region]). Absolute OS advantage increased over time for ITT low-risk (LI + CIZ + SOC)-treated vs. ITT low-risk SOC: reaching 14.1% (62.7% vs. 48.6%) at 60 months, with 46.5 months median OS advantage (101.7 months vs. 55.2 months), respectively. Quality of life benefit for complete responders sustained for >3 years post LI treatment. Percent treatment-emergent adverse events were comparable among all treated groups. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35.

In the general population, the causes of exposure to 4-aminobiphenyl are cigarette smoking and passive inhalation of tobacco. 4-Aminobiphenyl can occur as a contaminant in 2-aminobiphenyl, which is used in the manufacture of dyes. Other potential sources include aniline, drugs, cosmetics, color additives in food, clothes, and hair dyes. 4-Aminobiphenyl has also been found as a contaminant in diphenylamine, a fungicide used on apples, as well as in cooking oil fumes. Living near places contaminated with benzidine can lead to exposure, as certain bacteria can degrade benzidine in the environment to 4-aminobiphenyl. There are likely other sources of environmental exposure, as biomarkers derived from aromatic amines, such as hemoglobin adducts or metabolites in urine, have also been identified in nonsmokers not occupationally exposed to these chemicals. 4-Aminobiphenyl causes bladder cancer and is carcinogenic to humans. Its urinary metabolites are N-hydroxy-4-aminobiphenyl, N-glucuronides, and 4-aminobiphenyl-DNA adducts.

The general population may be exposed to benzidine through contact with leather products, clothing, and toys containing benzidine or benzidine-based paints. The food dyes tartrazine and sunset yellow contain trace amounts of benzidine (within nanograms per gram of food). The production and use of benzidine in the production of paints has been recorded in some developing countries. Exposure to benzidine through ingestion is unlikely, but other impurities in synthetic dyes may be metabolized to benzidine after ingestion. Benzidine causes bladder cancer. Its urinary metabolites are benzidine and benzidine conjugates (monoacetylbenzidine).

Air contamination with lindane is the result of pesticide application and dust emissions from production facilities. Lindane enters water through agricultural and forestry use, precipitation, and to a lesser extent occasional pollution of wastewater from manufacturing plants. Lindane can be released into the soil by direct pesticide application. Lindane is mobile, and as a result of atmospheric transport over long distances, it is deposited worldwide. Current exposure of the general population occurs mainly through diet. The largest number of data refer to non-Hodgkin’s lymphoma (NHL). Its urinary metabolites are chlorophenols.

The highest concentrations of arsenic were found in seafood, meat, cereals, vegetables, fruit, and dairy products. Inorganic arsenic is the dominant form and is found in meat, poultry, dairy products, and grains. Uses of arsenic today include pharmaceuticals, wood preservatives, agricultural chemicals, mining, metallurgical, glass, and semiconductor applications. The primary route of exposure of the general population to arsenic is through consumption of contaminated food or water. Inorganic arsenic compounds cause lung, bladder, and skin cancer. Also, a positive association was observed between exposure to arsenic and inorganic arsenic compounds and cancer of the kidney, liver, and prostate. Chronic exposure of humans to inorganic arsenic has been associated with increased risk of disorders of the peripheral vasculature, diseases of the cardiovascular and cerebrovascular systems, hypertension, diabetes, and reproductive failure. Urinary arsenic metabolites commonly used as indicators of recent exposure are total inorganic arsenic, arsenobetaine, methylarsonic acid (MAA), and dimethylarsinic acid (DMAA).

Beryllium is used in aerospace (altimeters, braking systems, engines, precision tools, solid propellant additives, satellite optical system mirror components, gyroscopes), automotive (air bag sensors, antilock systems, steering linkage springs), biomedicine (dental crowns, medical laser components, X-ray tube windows), defense (heat shields, missile guidance systems, nuclear reactor components, advanced surveillance satellites, and radar systems), energy and electronics (heat exchanger tubes, microwave devices, relays and switches), fire prevention (non-sparking tools in oil exploration equipment, sprinkler system springs), consumer products (camera shutters, computer disks, pencil clips), production of plastics (plastic injection molds), sporting goods (golf clubs, fishing rods, natural and artificial precious stones), and telecommunications (components for mobile phones, electronic and electrical connectors, housings for underwater repeaters). Beryllium oxide is suitable for the production or protection of materials used at high temperatures in corrosive environments (it has ceramic properties). Beryllium and beryllium compounds cause cancerous diseases. Beryllium was detected in granulomas associated with chronic beryllium disease in exposed workers for several years. This indicates that beryllium is retained in granulomatous lesions for a long period of time in exposed humans. Inflammatory processes associated with the development of acute or chronic beryllium disease contribute to the development of lung cancer. In analytical papers, no one mentions metabolites, but they are determined as elements after destroying samples and releasing them from complexes with proteins where they are bound.

Aristolochia acids (AAs) are found in the Aristolochiaceae family, which includes about 500 species, spread all around the world, with most of the taxa in the tropical region and are widely used as herbal remedies. In the 1990s, their use for weight loss in developed countries was prohibited or strictly limited. Since then, AAs have been produced commercially only as a reference standard and as research chemicals. The occurrence of AAs in either the above- or underground parts of vegetables is attributed to a specific passage route that could explain how AAs are transported within the environment. Some results show that AAs’ presence is attributed to the growing of A. clematitis in the area, and in general, the highest concentrations are found in the soil samples, and the lowest concentrations in cucumber and fruit, but without a direct correlation to the distance (or 50 cm) from the Aristolochia plants. Aristolochic acid adducts and DNA were found in urothelial tissue samples from all urothelial cancer patients with Chinese herbal nephropathy. Their urinary metabolites are aristolactam I (a metabolite of aristolochic acid I) and aristolactam II (a metabolite of aristolochic acid II). Apart from aristolactam, DNA adducts are also their urinary metabolites.

Ethylene oxide is a raw material used as a base substance for the production of important derivatives, including di-, tri-, and poly(ethylene) glycols, cellulose and poly(propylene) glycol, ethylene glycol ethers, ethanol-amines, fatty alcohol products and fatty amines, and alkyl phenols. A very small part of the production of ethylene oxide is used directly in gaseous form as a sterilization agent, fumigant, and insecticide (alone or in a mixture with nitrogen, carbon dioxide, or dichlorofluoromethane). Ethylene oxide is used to sterilize drugs, hospital equipment, disposable and reusable medical items, packaging materials, food, books, museum objects, scientific equipment, clothing, furs, wagons, airplanes, and beehives. Additional nonoccupational sources of ethylene oxide exposure are tobacco, residues in spices, and skin care products, in very small amounts. Ethylene oxide is produced during the burning of fossil fuel. There is a causal relationship between exposure to ethylene oxide and the occurrence of lymphatic and hematopoietic cancers (non-Hodgkin’s lymphoma, multiple myeloma, and chronic lymphocytic leukemia) and breast cancer. Its urinary carcinogen indicators are S-(2-hydroxyethyl)glutathione and N-acetyl-S-(2-hydroxyethyl)-L-cysteine (hydroxyethyl mercapturic acid [HEMA])—conjugates with glutathione, as well as ethylene glycol.

The products of coal tar distillation consist of a complex mixture of mono- and polycyclic aromatic hydrocarbons and resin (Betts WD, Tar and pitch. In: Kirk-Othmer encyclopedia of chemical technology, 5th edn. Wiley, New York, 1997). By the 1990s, coal tar became the main source of anticorrosive coatings and wood preservatives. Some authors reported very high death rates from scrotal cancer among coal tar distillers, and a French study showed a significant increase in the incidence of oral cavity and pharyngeal cancer. Epidemiological studies are consistent that occupational exposure during tar distillation is carcinogenic to humans and causes lung cancer. Its most representative urinary metabolite is 1-hydroxypyrene.

Oil shale is found in many parts of the world, and the world’s total recoverable resources are estimated at 2.6 trillion barrels. They have been used in the production of fuel oil for gas turbines, automobile gasoline, and additives for petroleum fuel oil with a high sulfur content. In the People’s Republic of China, shale oil has been used as raw material for refineries and for electricity generation. They can also be used to produce gasoline, kerosene, diesel fuel, and coke. Oil shale industries operate in Europe (Estonia), South America (Brazil), and Asia (China). The largest use is in Estonia—in northeastern Estonia, about 85% of this material is burned as fuel in electric power plants, and the rest is returned for shale oil and used for the production of fuel and petrochemical products. Exposure to shale oil causally linked to skin cancer, especially scrotal cancer. 1-Hydroxypyrene is the most representative urinary metabolite from shale oils.

Approximately, yearly and globally, almost 20 million people get sick and almost 10 million people die from all cancers. This book elaborates the chemical elements and chemical compounds that very probably contribute to both cancer occurrence in over 13.5 million people and death from cancer in over seven million people. Moreover, chemical elements and chemical compounds very probably contribute to cancer occurrence in about 68% of all cancer cases and very probably significantly contribute to cancer death in about 72% of all cancer deaths. Carcinogenesis may last decades, and before malignant disease occurs, many other nonmalignant diseases (the most frequent are cardiovascular diseases, endocrinological diseases, neurological diseases, hematological diseases, and dermatological diseases) appear caused or supported by chemical carcinogens (Table 1). Because of growing of world population and unproportional growing of the elderly population, consequently, by 2050, the number of cancer cases is predicted to reach 35 million. This publication offers to the user a highly effective, affordable, applicable, noninvasive, quick, and cheap method to avoid or reduce one’s exposure to the most dangerous chemical carcinogens.

Consumer products that contain trichlorethylene are automotive products, highly processed wood, cleaning and polishing agents, chemicals in the leather industry, adhesives, paint-related products, and lubricants. The main use of trichlorethylene is in metal degreasing in all metalworking and maintenance operations to remove oil, grease, waxes, tars, and moisture prior to final surface treatments such as galvanizing, painting, anodizing, and conversion coating applications. Trichlorethylene is used in degreasing in five major industrial groups: furniture and fixtures, finished metal products, electrical and electronic equipment, transportation equipment, and various manufacturing industries. It is also used in the production of plastics, appliances, jewelry, automobiles, plumbing, textiles, paper, glass, and printing. Trichloroethylene is rapidly and extensively absorbed following all routes of exposure and is primarily found in adipose tissue, the brain, muscle, heart, kidney, and liver. Human and animal studies have identified numerous noncancer adverse effects of TCE, including immune dysfunction and nervous system, renal, and liver toxicity. Trichlorethylene causes kidney cancer, liver cancer, and non-Hodgkin’s lymphoma. Increased risks at other sites are also suspected, including cancers of the liver, prostate, bladder, and esophagus. Some findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks. Its urinary metabolites are trichloroethanol (THE) and trichloroacetic acid (THAA).

BHME and HMME are primarily used as chemical intermediates and alkylating agents. BHME is used as a laboratory reagent in the production of plastics, ion exchange resins, and polymers. Uses of BHME include the cross-linking of cellulose, the preparation of styrene and other polymers, the surface treatment of vulcanized rubber to increase adhesion, and the production of flame-resistant fabrics. HMME is used as an alkylating agent and industrial solvent for the production of dodecylbenzyl chloride, water repellents, ion exchange resins and polymers, and a chloromethylation reagent. The most likely source of exposure to BHME is during the production or use of chemicals, where it may be present as a contaminant or formed unintentionally. Bis(chloromethyl)ether and chloromethyl methyl ether (technical grade) cause lung cancer. BHME and HMME are subject to rapid hydrolysis to formaldehyde and hydrochloric acid. A specific, persistent, and reliable urinary metabolite is not known.

4,4′-Methylenebis(2-chloroaniline) abbreviated MOCA is used for coatings and cast polyurethanes. The general population can be exposed to MOCA if they live or spend time on land contaminated with it. Drinking water or eating certain types of plants (root crops) grown in an area contaminated with MOCA can significantly expose the population. Even immediate family members of MOCA-exposed workers may be affected by MOCA concentrations in urine of up to 15 μg/l. It is used as a curing agent for isocyanate-containing polymers, and only about 1% is used in epoxy/epoxy-urethane resin blends, for curing castable liquid polyurethane elastomers. MBOCA-cured polyurethanes have been used to produce shoe soles, rolls for postage stamp machines, cutting bars in plywood manufacturing, rolls and belt drives in cameras, computers, wheels and pulleys for escalators and elevators, in the manufacture of gun mounts, jet engine turbine blades, radar systems, components in home appliances, as a wiring patting, ball seals on nuclear submarines, positioning strips in “Poseidon” missiles, and castable urethane rubber products, such as absorption pads, conveyor belts, and encapsulation of electric components. MOCA causes an increased incidence of bladder tumors in exposed workers. MOCA and conjugates are urinary carcinogen indicators for 4,4′-methylenebis(2-chloroaniline).

PHBs are found worldwide in all parts of the environment (soil, water, air), in wildlife, and in the human body (at measurable levels). Humans are mainly exposed to PHBs through contaminated food and to a lesser extent through inhalation and dermal absorption. The main sources of PHBs indoors are sealants, paints, floor sealants, ballasts in lighting fixtures, and contaminated dust. PHBs can migrate into surrounding materials, such as concrete or wood, and into indoor air. In the USA, indoor air concentrations of PHBs have been reported to be from five to 300 times higher than those in outdoor air, and that concentrations are higher in older buildings. In Europe, the highest indoor concentrations are found in buildings built between 1960 and 1975, sealed with elastic materials containing PHB. Mortality from cancer of the digestive tract has statistically significantly increased. Deaths from lymphoma cancer were on the rise, especially from Hodgkin’s disease in women. Men were at increased risk of mortality from biliary tract cancer and prostate cancer. Urinary metabolites for 2,3,4,7,8-pentachlorodibenzofuran are methoxy-pentaHDF and dimethoxy-pentachlorobiphenyl.

Orthotoluidine is used as an intermediate in the synthesis of herbicides, more than 90 colors and pigments, for synthetic rubber, pharmaceutical products, pesticides, and in the clinical laboratory as an ingredient in reagents for glucose analysis and tissue staining. Significant nonoccupational exposure to orthotoluidine may result from the use of some hair dyes, the local anesthetic prilocaine, or tobacco smoke. Orthotoluidine causes bladder cancer. Its urinary metabolites are orthotoluidine and its conjugates and N-acetyl-ortho-toluidine.

According to FAO data, aflatoxins contaminate a quarter of the world’s crops annually. The temperature at which most aflatoxins are produced is 33 °C. Due to the movement of agricultural products around the world, no region is free of aflatoxin. Aflatoxins B1, B2, G1, and G2 can be collected in dust in food processing plants (cocoa, coffee, and spices). The risk of hepatocellular carcinoma (HCC) is significantly increased for subjects with high urinary concentrations of aflatoxin metabolites. Their urinary metabolites are aflatoxin-N7-guanine adducts in urine.

Vinyl chloride is released into the environment from the plastics industry—emissions to the atmosphere or wastewater in surface waters. Also, it is released as a product of decomposition of chlorinated solvents in landfills as landfill gas. Also, in daily life, VCM is released from plastic bottles, toys, kitchen utensils, food wrappers, wallpaper, pipes, car interiors, bathroom tiles, and cigarettes. Vinyl chloride is used to a lesser extent in the production of chlorinated solvents and the production of ethylene diamine for the production of resins. The general population can be exposed to VCM/PVC through inhalation of contaminated air, ingestion of contaminated drinking water, consumption of contaminated food, and dermal contact. Vinyl chloride causes liver angiosarcoma and hepatocellular carcinoma. Its urinary metabolites are vinyl chloride and thiodiglycolic acid.