BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

• Klíčová slova
• Africa, Demographics, Geostatistics, HIV, HIV prevalence, Mapping, Spatial statistics,
• MeSH
• AIDS * epidemiologie   MeSH
• dospělí MeSH
• HIV infekce * prevence a kontrola   MeSH
• HIV MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prevalence MeSH
• séroepidemiologické studie MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• subsaharská Afrika epidemiologie   MeSH

BACKGROUND: Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. METHODS: We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. RESULTS: In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. CONCLUSIONS: Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

• Klíčová slova
• Burden of disease, Disability adjusted life years, Europe, Injuries, Mortality,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. METHODS: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. FINDINGS: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 - 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432-912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9-412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (-29·1%;23·8-38·5). YLLs decreased in self-harm (-27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. INTERPRETATION: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. FUNDING: The Bill and Melinda Gates Foundation.

• Klíčová slova
• Europe, Mental disorders, Mental health, Self-harm, Substance use, Young people,
• Publikační typ
• časopisecké články MeSH

Sphingolipids (SLs) are important signaling molecules and functional components of cellular membranes. Although SLs are known as crucial regulators of neural cell physiology and differentiation, modulations of SLs by environmental neurotoxicants in neural cells and their neuronal progeny have not yet been explored. In this study, we used in vitro models of differentiated neuron-like cells, which were repeatedly exposed during differentiation to model environmental toxicants, and we analyzed changes in sphingolipidome, cellular morphology and gene expression related to SL metabolism or neuronal differentiation. We compared these data with the results obtained in undifferentiated neural cells with progenitor-like features. As model polychlorinated organic pollutants, we used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3'-dichlorobiphenyl (PCB11) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153). PCB153 revealed itself as the most prominent deregulator of SL metabolism and as potent toxicant during early phases of in vitro neurogenesis. TCDD exerted only minor changes in the levels of analysed lipid species, however, it significantly changed the rate of pro-neuronal differentiation and deregulated expression of neuronal markers during neurogenesis. PCB11 acted as a potent disruptor of in vitro neurogenesis, which induced significant alterations in SL metabolism and cellular morphology in both differentiated neuron-like models (differentiated NE4C and NG108-15 cells). We identified ceramide-1-phosphate, lactosylceramides and several glycosphingolipids to be the most sensitive SL species to exposure to polychlorinated pollutants. Additionally, we identified deregulation of several genes related to SL metabolism, which may be explored in future as potential markers of developmental neurotoxicity.

• Klíčová slova
• Ceramide-1-phosphate, Environmental neurotoxicants, Lactosylceramide, Neurogenesis, Sphingolipids,
• MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné linie MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• neurogeneze účinky léků   MeSH
• neurony účinky léků   metabolismus   MeSH
• neurotoxické syndromy etiologie   genetika   MeSH
• polychlorované bifenyly farmakologie   toxicita   MeSH
• polychlorované dibenzodioxiny toxicita   MeSH
• sfingolipidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 2,4,5,2',4',5'-hexachlorobiphenyl MeSH Prohlížeč
• 3,3'-dichlorobiphenyl MeSH Prohlížeč
• látky znečišťující životní prostředí MeSH
• polychlorované bifenyly MeSH
• polychlorované dibenzodioxiny MeSH
• sfingolipidy MeSH

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

• Klíčová slova
• descriptive epidemiology, methodology, populations/contexts, statistical issues,
• MeSH
• celosvětové zdraví * MeSH
• globální zátěž nemocemi * MeSH
• incidence MeSH
• kvalitativně upravené roky života MeSH
• lidé MeSH
• morbidita MeSH
• naděje dožití MeSH
• rány a poranění * mortalita   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

OBJECTIVE: "Krokodil" is the street name for an impure homemade drug mixture used as a cheap substitute for heroin, containing desomorphine as the main opioid. Abscesses, gangrene, thrombophlebitis, limb ulceration and amputations, jaw osteonecrosis, skin discoloration, ulcers, skin infections, and bleeding are some of the typical reported signs in humans. This study aimed to understand the toxicity of krokodil using Wistar male rats as experimental model. METHODS: Animals were divided into seven groups and exposed subcutaneously to NaCl 0.9% (control), krokodil mixture free of psychotropic substances (blank krokodil), pharmaceutical grade desomorphine 1 mg/kg, and four different concentrations of krokodil (containing 0.125, 0.25, 0.5, and 1 mg/kg of desomorphine) synthesized accordingly to a "domestic" protocol followed by people who inject krokodil (PWIK). Daily injections for five consecutive days were performed, and animals were sacrificed 24 hr after the last administration. Biochemical and histological analysis were carried out. RESULTS: It was shown that the continuous use of krokodil may cause injury at the injection area, with formation of necrotic zones. The biochemical results evidenced alterations on cardiac and renal biomarkers of toxicity, namely, creatine kinase, creatine kinase-MB, and uric acid. Significant alteration in levels of reduced and oxidized glutathione on kidney and heart suggested that oxidative stress may be involved in krokodil-mediated toxicity. Cardiac congestion was the most relevant finding of continuous krokodil administration. CONCLUSIONS: These findings contribute notably to comprehension of the local and systemic toxicological impact of this complex drug mixture on major organs and will hopefully be useful for the development of appropriate treatment strategies towards the human toxicological effects of krokodil.

• Klíčová slova
• desomorphine, in vivo, krokodil, phosphorous, toxicity,
• MeSH
• injekce subkutánní MeSH
• játra účinky léků   patologie   MeSH
• kodein aplikace a dávkování   analogy a deriváty   toxicita   MeSH
• kožní nemoci chemicky indukované   patologie   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   patologie   MeSH
• lidé MeSH
• nekróza chemicky indukované   patologie   MeSH
• opioidní analgetika aplikace a dávkování   toxicita   MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• plíce účinky léků   patologie   MeSH
• potkani Wistar MeSH
• srdce účinky léků   MeSH
• tkáňová distribuce účinky léků   fyziologie   MeSH
• velikost orgánu účinky léků   fyziologie   MeSH
• zakázané drogy toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• desomorphine MeSH Prohlížeč
• kodein MeSH
• opioidní analgetika MeSH
• zakázané drogy MeSH

"Krokodil" is the street name for a drug, which has been attracting media and researchers attention due to its increasing spread and extreme toxicity. "Krokodil" is a homemade injectable mixture being used as a cheap substitute for heroin. Its use begun in Russia and Ukraine, but it is being spread throughout other countries. The starting materials for "krokodil" synthesis are tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants and red phosphorus from matchboxes, all of which are easily available in a retail market or drugstores. The resulting product is a light brown liquid that is injected without previous purification. Herein, we aimed to understand the chemistry behind "krokodil" synthesis by mimicking the steps followed by people who use this drug. The successful synthesis was assessed by the presence of desomorphine and other two morphinans. An analytical gas chromatography-electron impact/mass spectrometry (GC-EI/MS) methodology for quantification of desomorphine and codeine was also developed and validated. The methodologies presented herein provide a representative synthesis of "krokodil" street samples and the application of an effective analytical methodology for desomorphine quantification, which was the major morphinan found. Further studies are required in order to find other hypothetical by-products in "krokodil" since these may help to explain signs and symptoms presented by abusers.

• Klíčová slova
• Desomorphine, GC-EI/MS analysis, Opioid abuse, “Krokodil” synthesis,
• MeSH
• chromatografie kapalinová MeSH
• intravenózní abúzus drog MeSH
• kodein analogy a deriváty   analýza   chemická syntéza   MeSH
• lidé MeSH
• limita detekce MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• soudní toxikologie MeSH
• zakázané drogy chemická syntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• desomorphine MeSH Prohlížeč
• kodein MeSH
• zakázané drogy MeSH

"Krokodil" is the street name for the homemade injectable mixture that has been used as a cheap substitute for heroin. Its use begun in Russia and Ukraine and nowadays is being spread over several other countries. Desomorphine is the semi-synthetic opioid claimed to be the main component of krokodil and considered to be responsible for its psychoactive characteristics. The starting materials for desomorphine synthesis are codeine tablets, alkali solutions, organic solvent, acidified water, iodine and red phosphorus, all of which are easily available in retail outlets, such as supermarkets, drugstores, etc. The resulting product is a light brown liquid that is called krokodil. People who inject krokodil present a great variety of serious signs and symptoms, including thrombophlebitis, ulcerations, gangrene, and necrosis, quickly evolving to limb amputation and death. These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis. In this work, we reviewed several aspects of krokodil use, including its epidemiology, pharmacology and the chemical properties of the main active ingredient (desomorphine). To enhance our understanding of the clinical and toxic effects and to support the implementation of harm reduction measures, we also describe the "bathtub chemistry" of krokodil and the content of the final solution.

• Klíčová slova
• Desomorphine, Krokodil synthesis, Opioids, People who inject drugs, Signs and symptoms,
• MeSH
• gangréna chemicky indukované   MeSH
• intravenózní abúzus drog komplikace   MeSH
• kodein škodlivé účinky   analogy a deriváty   chemie   MeSH
• kůže patologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nekróza chemicky indukované   MeSH
• neurotoxické syndromy etiologie   MeSH
• osteonekróza chemicky indukované   MeSH
• traumatická amputace chemicky indukované   MeSH
• zakázané drogy škodlivé účinky   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• desomorphine MeSH Prohlížeč
• kodein MeSH
• zakázané drogy MeSH