| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Bryazka, D., et al.
(författare)
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Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
- 2022
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Ingår i: Lancet. - 0140-6736. ; 400:10347, s. 185-235
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Tidskriftsartikel (refereegranskat)abstract
- Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 5. |
- Chudinova, E., et al.
(författare)
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Functionalization of additive-manufactured Ti6Al4V scaffolds with poly(allylamine hydrochloride)/poly(styrene sulfonate) bilayer microcapsule system containing dexamethasone
- 2021
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Ingår i: Materials Chemistry and Physics. - : Elsevier BV. - 0254-0584 .- 1879-3312. ; 273
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Tidskriftsartikel (refereegranskat)abstract
- Porous titanium alloy Ti6Al4V scaffolds manufactured via electron beam melting (EBM®) reveal broad prospects for applications in bone tissue engineering. However, local inflammation and even implant failure may occur while placing an implant into the body. Thus, the application of drug carriers to the surface of a metallic implant can provide treatment at the inflammation site. In this study, we propose to use polyelectrolyte (PE) microcapsules formed by layer-by-layer (LbL) synthesis loaded with both porous calcium carbonate (CaCO3) microparticles and the anti-inflammatory drug dexamethasone (DEX) to functionalize implant surfaces and achieve controlled drug release. Scanning electron microscopy indicated that the CaCO3 microparticles coated with PE bilayers loaded with DEX had a spherical shape with a diameter of 2.3 ± 0.2 μm and that the entire scaffold surface was evenly coated with the microcapsules. UV spectroscopy showed that LbL synthesis allows the manufacturing of microcapsules with 40% DEX. According to high performance liquid chromatography (HPLC) analysis, 80% of the drug was released within 24 h from the capsules consisting of three bilayers of polystyrene sulfonate (PSS) and poly(allylamine)hydrochloride (PAH). The prepared scaffolds functionalized with CaCO3 microparticles loaded with DEX and coated with PE bilayers showed hydrophilic surface properties with a water contact angle below 5°. Mouse embryonic fibroblast cells were seeded on Ti6Al4V scaffolds with and without LbL surface modification. The surface modification with LbL PE microcapsules with CaCO3 core affected cell morphology in vitro. The results confirmed that DEX had no toxic effect and did not prevent cell adhesion and spreading, thus no cytotoxic effect was observed, which will be further studied in vivo.
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| 6. |
- Dehasque, Marianne, et al.
(författare)
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Temporal dynamics of woolly mammoth genome erosion prior to extinction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A large number of species have recently recovered from near-extinction events. Understanding the genetic consequences of severe population declines followed by demographic recoveries is key to predict the long-term viability of species in order to mitigate future extinction risks. Although these species have avoided the immediate extinction threat, their long-term viability remains questionable due to the genetic consequences of population declines, which are not understood on a time scale beyond a few generations. The woolly mammoth (Mammuthus primigenius) population on Wrangel Island is an excellent model system to investigate long-term genetic consequences of a population bottleneck. Mammoths became isolated on the island in the early Holocene due to rising sea levels, and persisted for over 200 generations (~6,000 years) before becoming extinct ~4,000 years ago. To study the evolutionary processes leading up to the extinction of the woolly mammoth on the island, we analysed 21 Siberian woolly mammoth genomes, including that of one of the last known mammoths. Our results show that the Wrangel Island mammoths recovered quickly from an initially severe bottleneck, and subsequently remained demographically stable during the ensuing 6 millennia. Further, we find that highly deleterious mutations were gradually purged from the population, whereas there was an accumulation of mildly deleterious mutations. The gradual purging of highly deleterious mutations suggests an ongoing inbreeding depression that lasted for hundreds of generations. This time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked present-day populations.
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| 7. |
- Hasnowo, Lutfi A., et al.
(författare)
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Synthesis, I-123-Radiolabeling Optimization, and Initial Preclinical Evaluation of Novel Urea-Based PSMA Inhibitors with a Tributylstannyl Prosthetic Group in Their Structures
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:15
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine & epsilon;-nitrogen atom, a dipeptide including two phenylalanine residues in the L-configuration as the peptide fragment of the linker, and 3- or 4-(tributylstannyl)benzoic acid as a prosthetic group in their structures for radiolabeling. The standard compounds [I-127]PSMA-m-IB and [I-127]PSMA-p-IB for comparative and characterization studies were first synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach, in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence followed by replacement of the Sn(Bu)(3) group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [I-123]PSMA-p-IB was higher than that of [I-123]PSMA-m-IB, which were 74.9 & PLUSMN; 1.0% and 49.4 & PLUSMN; 1.2%, respectively. The radiochemical purity of [I-123]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [I-123]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [I-123]PSMA-p-IB showed less accumulation than [Lu-177]Lu-PSMA-617 in several normal organs (liver, kidney, and bone). These results warrant further preclinical development, including toxicology evaluation and experiments in tumor-bearing mice.
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| 8. |
- Larsson, Petter, et al.
(författare)
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Consequences of past climate change and recent human persecution on mitogenomic diversity in the arctic fox
- 2019
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 374:1788
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Tidskriftsartikel (refereegranskat)abstract
- Ancient DNA provides a powerful means to investigate the timing, rate and extent of population declines caused by extrinsic factors, such as past climate change and human activities. One species probably affected by both these factors is the arctic fox, which had a large distribution during the last glaciation that subsequently contracted at the start of the Holocene. More recently, the arctic fox population in Scandinavia went through a demographic bottleneck owing to human persecution. To investigate the consequences of these processes, we generated mitogenome sequences from a temporal dataset comprising Pleistocene, historical and modern arctic fox samples. We found no evidence that Pleistocene populations in mid-latitude Europe or Russia contributed to the present-day gene pool of the Scandinavian population, suggesting that postglacial climate warming led to local population extinctions. Furthermore, during the twentieth-century bottleneck in Scandinavia, at least half of the mitogenome haplotypes were lost, consistent with a 20-fold reduction in female effective population size. In conclusion, these results suggest that the arctic fox in mainland Western Europe has lost genetic diversity as a result of both past climate change and human persecution. Consequently, it might be particularly vulnerable to the future challenges posed by climate change. This article is part of a discussion meeting issue 'The past is a foreign country: how much can the fossil record actually inform conservation?'
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| 9. |
- Louarn, P., et al.
(författare)
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Multiscale views of an Alfvenic slow solar wind : 3D velocity distribution functions observed by the Proton-Alpha Sensor of Solar Orbiter
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Alfvenic slow solar wind is of particular interest, as it is often characterized by intense magnetic turbulence, complex proton 3D velocity distribution functions (VDF), and an ensuing richness of kinetic and dynamic processes.Aims. We take advantage of the fast time cadence of measurements taken by the Proton-Alpha Sensor (PAS) on board Solar Orbiter to analyze the kinetic properties of the proton population, the variability of their VDFs, and the possible link with propagating magnetic structures. We also study the magnetic (B) and velocity (V) correlation that characterizes this type of wind down to the ion gyroperiod.Methods. We analyzed the VDFs measured by PAS, a novelty that take advantages of the capability of 3D measurements at a 4 Hz cadence. In addition, we considered MAG observations.Results. We first show that there is a remarkable correlation between the B and V components observed down to timescales approaching the ion gyrofrequency. This concerns a wide variety of fluctuations, such as waves, isolated peaks, and discontinuities. The great variability of the proton VDFs is also documented. The juxtaposition of a core and a field-aligned beam is the norm but the relative density of the beam, drift speed, and temperatures can considerably change on scales as short as as a few seconds. The characteristics of the core are comparatively more stable. These variations in the beam characteristics mostly explain the variations in the total parallel temperature and, therefore, in the total anisotropy of the proton VDFs. Two magnetic structures that are associated with significant changes in the shape of VDFs, one corresponding to relaxation of total anisotropy and the other to its strong increase, are analyzed here. Our statistical analysis shows a clear link between total anisotropy (and, thus, beam characteristics) and the direction of B with respect to the Parker spiral. In the present case, flux tubes aligned with Parker spiral contain an average proton VDF with a much more developed beam (thus, with larger total anisotropy) than those that are inclined, perpendicular, or even reverse with regard to the outward direction.Conclusions. These observations document the variability of the proton VDF shape in relation to the propagation of magnetic structures. This is a key area of interest for understanding of the effect of turbulence on solar wind dynamics.
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| 10. |
- Machulkin, Aleksei E., et al.
(författare)
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Synthesis and Preclinical Evaluation of Urea-Based Prostate-Specific Membrane Antigen-Targeted Conjugates Labeled with 177Lu
- 2024
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Ingår i: ACS pharmacology & translational science. - : American Chemical Society (ACS). - 2575-9108. ; 7:5, s. 1457-1473
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Tidskriftsartikel (refereegranskat)abstract
- 177Lu-labeled small-molecule prostate-specific membrane antigen (PSMA) targeted tracers are therapeutic agents for metastatic castration-resistant prostate cancer. Optimizing molecular design holds the potential to further enhance the pharmacokinetic properties of PSMA-targeted agents while preserving their potent therapeutic effects. In this study, six novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL) urea-based PSMA ligand 2,2′,2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid conjugates were synthesized. These conjugates feature polypeptide linkers containing the Phe-Phe peptide sequence and an aromatic fragment at the ε-NH-Lys group of the DCL fragment. The synthesis yielded products with satisfactory yields ranging from 60% to 72%, paving the way for their preclinical evaluation. The labeling of the new variants of urea-based PSMA inhibitors provided a radiochemical yield of over 95%. The 177Lu-labeled conjugates demonstrated specific and moderate affinity binding to PSMA-expressing human cancer cells PC3-pip in vitro and specific accumulation in PSMA-expressing xenografts in vivo. Based on the results, both the lipophilicity and the type of substituent in the linker significantly influence the binding properties of the PSMA inhibitor and its biodistribution profile. Specifically, the studied variants containing a bromine substituent or a hydroxyl group introduced into the aromatic fragment of the phenylalanyl residue in DCL exhibit higher affinities to PSMA compared to variants with only a chlorine-substituted aromatic fragment or variants without any substituents. The [177Lu]Lu-13C with the bromine substituent was characterized by the highest activity accumulation in blood, salivary glands, muscle, bone, and gastrointestinal tract and had inasmuch as an unfavorable pharmacokinetic profile. The negative charge of the carboxyl group in the phenyl moiety of the [177Lu]Lu-13A variant has demonstrated a positive effect on reducing the retention of activity in the liver and the kidneys (the ratio of tumor to kidneys was 1.3-fold). Low accumulation in normal tissues in vivo indicates that this novel PSMA-targeting inhibitor is a promising radioligand.
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