Evaluation of the national alcohol control strategy (Green Paper on Alcohol Policy) of Estonia

" Introduction: Estonia is a Baltic country with high adult alcohol per capita (APC) consumption. Since 2013, its alcohol control policy has been guided by the Green Paper on Alcohol Policy (GP), which is the equivalent of a non-binding national alcohol action plan. This contribution attempts to evaluate the overall impact of the GP on APC. Methods: For the overall evaluation, APC was quantitatively compared for three periods: pre-GP (2000-2012), the core period of the GP (2013-2019) and the COVID-19 phase (2020-2022), using Analysis of Variance. Results: APC decreased on average by 0.25 L of pure alcohol per year in the 7 years defined as the core period of the GP, whereas it increased in the other periods between 2001 and 2022 (period 2001-2012: +0.47 L; 2020-2022: +0.27 L). These differences were statistically significant (F [1, 18] = 5.22, p = 0.035). Moreover, there was no overall trend of decreasing APC during the core period of the GP in neighbouring countries (Latvia, Lithuania and Poland). Discussion and conclusions: The combination of the various measures of the national alcohol policy was associated with a marked decrease in APC."This evaluation was financially supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health project ‘Evaluation of the impact of alcohol control policies on morbidity and mortality in Lithuania and other Baltic states’ (Co-primary investigators: M. Štelemėkas and J. Rehm; R01AA028224) and by the WHO European Office and the WHO country office in Estonia

Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells

INTRODUCTION: Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways. METHODS: The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos. RESULTS: Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells. CONCLUSION: By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies

Onboard Planning and Scheduling Autonomy within the Scope of the FireBird Mission

For most low orbiting earth observation satellite missions, the timeline is generated on- ground and during dedicated uplink sessions the corresponding tele-commands are sent to the spacecraft. Bene�ts of this approach are easy maintainability of the complex planning software and quick response times to customer input. However this approach has two major drawbacks: On the one hand the spacecraft behavior is not completely predictable in terms of constraining resources, which means that even detailed modeling requires margins for the on-board resources within the on-ground scheduling algorithms. On the other hand, the reaction time to onboard detected events includes at least the two upcoming ground station contacts, since data downlink and evaluation, (re-)planning and tele-command uplink have to be awaited before the spacecraft can perform new activities. This paper describes the �nal design and use cases of VAMOS, an experiment of DLR/GSOC, which will be part of the FireBird mission. VAMOS consists of a combined onboard / on-ground planning system, which resolves the above mentioned drawbacks by supplying limited onboard autonomy to the satellite, retaining the bene�ts of a ground based planning system as far as possible

Dichlorobis(cycloalkylamine)platinum(II) complexes. Structure activity relationship on the human MDA-MB-231 breast cancer cell line

The syntheses of dichlorobis(cycloalkylamine)platinum(II) complexes with cis and trans cycloalkylamine ligands [cis-PtCl2(C3H5NH2)2 to cis-PtCl2(C8H15NH2)2 and trans-PtCl2(C7H13NH2)2 and trans-PtCl2(C8H15NH2)2 are described. The distinction between cis and trans isomers was achieved by 1H-NMR spectroscopy. The antitumor activity was detd. on the cell proliferation of the human MDA-MB-231 breast cancer cell line during long-term drug exposure. The complexes with small cycloalkylamine ligands were inferior, those with large cycloalkylamine ligands were comparable or superior to cisplatin. All cycloalkylamine ligands were inactive. IR spectroscopic studies showed that the size of the cycloalkylamine ring does not lead to significant differences in the Pt-Cl binding strength. Therefore it is assumed that the markedly stronger antitumor activity of the higher homologs is not the result of a faster reaction with bionucleophiles such as DNA. A possible explanation of the high activity of some of the isomers is the strong lipophilicity of the complexes. This assumption was confirmed by toxicity tests against confluent cultures