| 1. |
- Tran, K. B., et al.
(författare)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 2. |
- Alvarez, E. M., et al.
(författare)
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The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 23:1, s. 27-52
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Tidskriftsartikel (refereegranskat)abstract
- Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 4. |
- Ikuta, K. S., et al.
(författare)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Tidskriftsartikel (refereegranskat)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 17. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 18. |
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| 20. |
- Moortgat-Pick, G., et al.
(författare)
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Physics at the e(+) e(-) linear collider
- 2015
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 75:8
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Forskningsöversikt (refereegranskat)abstract
- A comprehensive review of physics at an e(+) e(-) linear collider in the energy range of root s = 92 GeV-3 TeV is presented in view of recent and expected LHC results, experiments from low-energy as well as astroparticle physics. The report focusses in particular on Higgs-boson, top-quark and electroweak precision physics, but also discusses several models of beyond the standard model physics such as super-symmetry, little Higgs models and extra gauge bosons. The connection to cosmology has been analysed as well.
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| 21. |
- Akeroyd, A. G., et al.
(författare)
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Prospects for charged Higgs searches at the LHC
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:5
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Forskningsöversikt (refereegranskat)abstract
- The goal of this report is to summarize the current situation and discuss possible search strategies for charged scalars, in non-supersymmetric extensions of the Standard Model at the LHC. Such scalars appear in Multi-HiggsDoublet models, in particular in the popular Two-HiggsDoublet model, allowing for charged and additional neutral Higgs bosons. These models have the attractive property that electroweak precision observables are automatically in agreement with the Standard Model at the tree level. For the most popular version of this framework, Model II, a discovery of a charged Higgs boson remains challenging, since the parameter space is becoming very constrained, and the QCD background is very high. We also briefly comment on models with dark matter which constrain the corresponding charged scalars that occur in these models. The stakes of a possible discovery of an extended scalar sector are very high, and these searches should be pursued in all conceivable channels, at the LHC and at future colliders.
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| 22. |
- Mahmoudi, H., et al.
(författare)
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A mediating role for mental health in associations between COVID-19-related self-stigma, PTSD, quality of life, and insomnia among patients recovered from COVID-19
- 2021
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Patients with COVID-19 often suffer from psychological problems such as post-traumatic stress disorder (PTSD) and self-stigmatization that may negatively impact their quality of life and sleep. This study examined mental health as a potential mediating factor linking self-stigmatization and PTSD to quality of life and sleep. Methods: Using a cross-sectional design, 844 people who had recovered from COVID-19 were called and interviewed. Data were collected using structured scales. Structural equation modeling was applied to assess fitness of a mediation model including self-stigma and PTSD as independent factors and quality of life and insomnia as dependent variables. Results: Mental health, COVID-19-related self-stigma, and mental quality of life were associated. Insomnia, PTSD, and COVID-19-related self-stigma displayed significant direct associations (r =.334 to 0.454; p <.01). A mediation model indicated satisfactory goodness of fit (CFI = 0.968, TLI = 0.950, SRMR = 0.071, RMSEA = 0.068). Mental health as a mediator had negative relationships with COVID-19-related self-stigma, PTSD, and insomnia and positive associations with quality of life. Conclusion: Mental health may mediate effects of COVID-19-related self-stigma and PTSD on quality of life and insomnia. Designing programs to improve mental health among patients with COVID-19 may include efforts to reduce negative effects of PTSD and COVID-19-related self-stigma on quality of life and insomnia.
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| 23. |
- Cepeda, D., et al.
(författare)
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CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer
- 2013
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018
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Tidskriftsartikel (refereegranskat)abstract
- SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
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| 27. |
- Yekaninejad, M. S., et al.
(författare)
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Exploring health literacy categories among an Iranian adult sample : a latent class analysis
- 2024
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- General and electronic health literacy are important factors engaging in healthy behaviors and maintaining good health. The present study explored demographic factors associated with general and electronic health literacy in the Iranian adult population. Via stratified cluster sampling, trained interviewers visited adult residents in Qazvin Province, Iran between January, and April 2022. The participants (N = 9775; mean age = 36.44 years; 6576 [67.3%] females) completed the Health Literacy Instrument for Adults (HELIA) assessing health literacy and the eHealth Literacy Scale (eHEALS) assessing electronic health literacy. Demographic data, including age, gender, educational level, marital status, and living location (city or rural), were collected. Latent class analysis (LCA) was used to classify the participants into different health literacy/electronic health literacy levels. The relationships between health literacy/electronic health literacy levels and demographic factors were examined using χ2 or analysis of variance. The LCA used HELIA scores to suggest five classes of health literacy and eHEALS scores to suggest three classes of electronic health literacy. For general and electronic health literacy, similar relationships were with demographic factors: females as compared with males had better general/electronic health literacy; younger people as compared with older people had better general/electronic health literacy; higher educational level was associated with better general/electronic health literacy; and city residents as compared with rural residents had better general/electronic health literacy. In conclusion, Iranian governmental agencies may wish to target on males, older adults, people with low educational level, and rural residents to improve their health literacy.
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| 28. |
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| 29. |
- Azhdarzadeh, M, et al.
(författare)
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Nanotoxicology: advances and pitfalls in research methodology
- 2015
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Ingår i: Nanomedicine (London, England). - : Future Medicine Ltd. - 1748-6963 .- 1743-5889. ; 10:18, s. 2931-2952
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Tidskriftsartikel (refereegranskat)abstract
- As research progresses, nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite this rise, their potential risks to human health, together with environmental issues, has led to increasing concerns regarding their use. As such, a comprehensive understanding of the interactions that occur at the nano-bio interface is required in order to design safe, reliable and efficient NPs for biomedical applications. To this end, extensive studies have been dedicated to probing the factors that define various properties of the nano-bio interface. However, the literature remains unclear and contains conflicting reports on cytotoxicity and biological fates, even for seemingly identical NPs. This uncertainty reveals that we frequently fail to identify and control relevant parameters that unambiguously and reproducibly determine the toxicity of nanoparticles, both in vitro and in vivo. An effective understanding of the toxicological impact of NPs requires the consideration of relevant factors, including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects and personalized protein corona. In this review, we discuss the factors that play a critical role in nano-bio interface processes and nanotoxicity. A proper combinatorial assessment of these factors substantially changes our insight into the cytotoxicity, distribution and biological fate of NPs.
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| 34. |
- Alijanzadeh, M., et al.
(författare)
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Fear of covid-19 and trust in the healthcare system mediates the association between individual’s risk perception and preventive covid-19 behaviours among iranians
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:22
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Tidskriftsartikel (refereegranskat)abstract
- Problems caused by the novel coronavirus disease-2019 (COVID-19) and its mutations have brought challenges in pandemic control for all countries worldwide. The present study examines the mediating roles of fear of COVID-19 and trust in the healthcare system in the association between individual’s risk perception and performing preventive COVID-19 behaviours among Iranians. A cross-sectional study design was used to collect data from 3652 residents of Qazvin province in Iran from 3 February to 15 April 2021 using a multistage stratified cluster sampling method. Participants responded to an online questionnaire concerning their fear of COVID-19, risk perception, trust in the healthcare system, and preventive COVID-19 behaviours. Small to medium positive interrelationships were observed between the variables of the study. Fear of COVID-19, trust in the healthcare system or both (fear of COVID-19 and trust in the healthcare system) mediated the association between an individual’s risk perception and performing preventive COVID-19 behaviours. The study demonstrated there are at least four ways through which an individual’s risk perception can influence preventive COVID-19 behaviours. Therefore, clinicians, health communicators, and researchers may capitalize on these findings to enhance preventive COVID-19 behaviours to help mitigate the spread of COVID-19 infection.
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| 40. |
- Kharazian, B, et al.
(författare)
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Bare surface of gold nanoparticle induces inflammation through unfolding of plasma fibrinogen
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 12557-
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Tidskriftsartikel (refereegranskat)abstract
- The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is now being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and therefore influence their biological fates, we hypothesized that the gold NP’s metal surface may also be involved in the observed Fg unfolding and inflammatory response. To mechanistically test this hypothesis, we probed the interaction of Fg with gold surfaces using molecular dynamic simulation (MD) and revealed that the gold surface has a capacity to induce Fg conformational changes in favor of inflammation response. As the integrity of coatings at the surface of ultra-small gold NPs are not thorough, we also hypothesized that the ultra-small gold NPs have a capacity to induce unfolding of Fg regardless of the composition and surface charge of their coatings. Using different surface coatings at the surface of ultra-small gold NPs, we validated this hypothesis. Our findings suggest that gold NPs may cause unforeseen inflammatory effects, as their surface coatings may be degraded by physiological activity.
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| 41. |
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| 42. |
- Mahmoudi Shamsabad, M, et al.
(författare)
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Impact of climate change implies the northward shift in distribution of the Irano-Turanian subalpine species complex Acanthophyllum squarrosum
- 2018
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Ingår i: Journal of Asia-Pacific Biodiversity. - : Elsevier BV. - 2287-884X. ; 11:4, s. 566-572
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we used maximum entropy modeling to predict the climate changeeffects on the distribution range of a subalpine steppe flora species complex, Acanthophyllum squarrosum (Caryophyllaceae). We used data from four different models, with two representative concentration pathways of climate scenarios in modern time, 2030, 2070 and 2080. Our results showed that A. squarrosum has a suitable habitat in ca. 1 million km² (33% of our study area) and will likely experience a northward shift, gaining new habitat in Azerbaijan, Armenia and North of Afghanistan in the near decades. Maxent model predicts A. squarrosum complex populations from southern Iran to be under treat of extinction, especially at lower altitudes regions and this prediction may concern other subalpine species found in the same region. Among the climatic variables investigated, annual mean temperature, and precipitation of warmest and coldest quarter were those that mostly affected A. squarrosum complex distribution.
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| 47. |
- Ahmady, M R, et al.
(författare)
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ESTIMATING THE ANNIHILATION DECAY B-s -> rho gamma WITH FACTORIZATION
- 2009
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Ingår i: Modern Physics Letters A. - 0217-7323 .- 1793-6632. ; 24:39, s. 3173-3181
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Tidskriftsartikel (refereegranskat)abstract
- The branching ratio for the rare two-body B-s -> rho gamma decay is calculated using the factorization assumption. This transition is dominated by the annihilation diagrams and, in principle, prone to receiving substantial contributions from new physics. We estimate Br(B-s -> rho gamma) approximate to 1.6 x 10(-9) within the Standard Model and investigate the sensitivity of this decay mode to the effects of two new physics scenarios: vector quark model and supersymmetry. Our results indicate that the shift in branching ratio is at most around 10% with the addition of vector quarks and is negligibly small in the constrained minimal supersymmetric extension of the Standard Model.
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| 48. |
- Akbari, Keramatollah, et al.
(författare)
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Simulation of ventilation effects on indoor radon
- 2013
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Ingår i: Management of environmental quality. - : Emerald. - 1477-7835 .- 1758-6119. ; 24:3, s. 394-407
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this paper is to describe the use of computational fluid dynamics (CFD) to simulate indoor radon distribution and ventilation effects. This technique was used to predict and visualize radon content and indoor air quality in a one-family detached house in Stockholm. The effects of intake fans, exhaust fans and doors on radon concentration were investigated. Design/methodology/approach: In this study a mechanically balanced ventilation system and a continuous radon monitor (CRM) were used to measure the indoor ventilation rate and radon levels. In a numerical approach, the FLUENT CFD package was used to simulate radon entry into the building and ventilation effects. Findings: Results of the numerical study indicated that indoor pressure created by ventilation systems and infiltration through doors or windows have significant effects on indoor radon content. The location of vents was found to affect the indoor radon level and distribution. Research limitations/implications: It may be possible to improve any discrepancies found in this article by using a more refined representation of grids and certain boundary conditions, such as pressure and temperature differences between inside and outside and by considering some real situations in residential buildings and external situations. Originality/value: From the viewpoints of indoor air quality (IAQ) and energy savings, ventilation has two opposing functions; on the positive side it enhances IAQ and the establishment of thermal comfort, and on the negative side it increases energy consumption. This paper describes the search for a solution to cope with this contradiction.
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| 49. |
- Allanach, Benjamin C., et al.
(författare)
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Simple and statistically sound strategies for analysing physical theories
- 2022
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Ingår i: Reports on progress in physics (Print). - : Institute of Physics Publishing (IOPP). - 0034-4885 .- 1361-6633. ; 85:5
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Forskningsöversikt (refereegranskat)abstract
- Physical theories that depend on many parameters or are tested against data from many different experiments pose unique challenges to statistical inference. Many models in particle physics, astrophysics and cosmology fall into one or both of these categories. These issues are often sidestepped with statistically unsound ad hoc methods, involving intersection of parameter intervals estimated by multiple experiments, and random or grid sampling of model parameters. Whilst these methods are easy to apply, they exhibit pathologies even in low-dimensional parameter spaces, and quickly become problematic to use and interpret in higher dimensions. In this article we give clear guidance for going beyond these procedures, suggesting where possible simple methods for performing statistically sound inference, and recommendations of readily-available software tools and standards that can assist in doing so. Our aim is to provide any physicists lacking comprehensive statistical training with recommendations for reaching correct scientific conclusions, with only a modest increase in analysis burden. Our examples can be reproduced with the code publicly available at Zenodo.
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| 50. |
- Alsiö, Johan, et al.
(författare)
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Enhanced Sucrose and Cocaine Self-Administration and Cue-Induced Drug Seeking after Loss of VGLUT2 in Midbrain Dopamine Neurons in Mice
- 2011
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 31:35, s. 12593-12603
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Tidskriftsartikel (refereegranskat)abstract
- The mesostriatal dopamine (DA) system contributes to several aspects of responses to rewarding substances and is implicated in conditions such as drug addiction and eating disorders. A subset of DA neurons has been shown to express the type 2 Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate. In the present study, we analyzed mice with a conditional deletion of Vglut2 in DA neurons (Vglut2(f/f;DAT-Cre)) to address the functional significance of the glutamate-DA cophenotype for responses to cocaine and food reinforcement. Biochemical parameters of striatal DA function were also examined by using DA receptor autoradiography, immediate-early gene quantitative in situ hybridization after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in which Vglut2 expression had been abrogated in DA neurons displayed enhanced operant self-administration of both high-sucrose food and intravenous cocaine. Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%, showing that reward-dependent plasticity is perturbed in these mice. In addition, several lines of evidence suggest that adaptive changes occurred in both the ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos were elevated as after cocaine induction. Furthermore, in vivo challenge of the DA system by potassium-evoked depolarization revealed less DA release in both striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons leads to perturbations of reward consumption as well as reward-associated memory, features of particular relevance for addictive-like behavior.
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