Criminally relevant conduct often falls under several criminal precepts, regulating as many criminal notions as possible, and it is necessary to decide whether all, some or only one of them could be ...applicable. This phenomenon, termed conflict, occurs when a subjects actions with criminal relevance are, wholly or partially, subsumed under different criminal precepts. To definitively classify the punishable act, it is then necessary to take a further step, which can be considered conclusive, and determine the precept or precepts applicable to the act. Hence, this paper analyses the meaning, content, and application of the conflict of laws and conflict of rules.
Czciej, ni mogoby si pocztkowo wydawa, zachowania noszce znamiona czynów zabronionych mog podlega wielu rónym przepisom prawa karnego, regulujcym moliwie jak najszerszy zakres poj karnych. Dlatego te ...niezbdne staje si ustalenie, czy w takim przypadku zastosowanie bd miay wszystkie te przepisy, ich cz czy te wycznie jeden z nich. Zjawisko to jest okrelane mianem kolizji: przypadku, w którym podmiot dopuszcza si jednego lub wicej czynu noszcego znamiona przestpstwa i takie czyny podlegaj, w caoci lub w czci, rónym przepisom prawa karnego. W tych okolicznociach, w celu ostatecznego ustalenia kwalifikacji czynu karalnego, naley wykona kolejny krok, który mona uzna za rozstrzygajcy, tj. wskaza przepis bd przepisy majce zastosowanie do tego czynu. Niniejsze opracowanie analizuje znaczenie, tre oraz zastosowanie kolizji przepisów i kolizji norm.
Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast ...cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (
)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (
)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (
). Furthermore,
affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (
) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (
)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (
) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.
The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in ...obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders.
We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed ...to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.
Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the
gene.
...codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (<0.5 Mb, 64/189) and
sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations (
or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with
variants
Our findings suggest that
plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed.
Purpose
This study aimed to determine the best strategy to achieve fast and safe extubation.
Methods
This multicenter trial randomized patients with primary respiratory failure and ...low-to-intermediate risk for extubation failure with planned high-flow nasal cannula (HFNC) preventive therapy. It included four groups: (1) conservative screening with ratio of partial pressure of arterial oxygen (PaO
2
) to fraction of inspired oxygen (FiO
2
) ≥ 150 and positive end-expiratory pressure (PEEP) ≤ 8 cmH
2
O plus conservative spontaneous breathing trial (SBT) with pressure support 5 cmH
2
O + PEEP 0 cmH
2
O); (2) screening with ratio of partial pressure of arterial oxygen (PaO
2
) to fraction of inspired oxygen (FiO
2
) ≥ 150 and PEEP ≤ 8 plus aggressive SBT with pressure support 8 + PEEP 5; (3) aggressive screening with PaO
2
/FiO
2
> 180 and PEEP 10 maintained until the SBT with pressure support 8 + PEEP 5; (4) screening with PaO
2
/FiO
2
> 180 and PEEP 10 maintained until the SBT with pressure support 5 + PEEP 0. Primary outcomes were time-to-extubation and simple weaning rate. Secondary outcomes included reintubation within 7 days after extubation.
Results
Randomization to the aggressive-aggressive group was discontinued at the interim analysis for safety reasons. Thus, 884 patients who underwent at least 1 SBT were analyzed (conservative-conservative group, n = 256; conservative-aggressive group, n = 267; aggressive-conservative group, n = 261; aggressive-aggressive, n = 100). Median time to extubation was lower in the groups with aggressive screening (p < 0.001). Simple weaning rates were 45.7%, 76.78% (205 patients), 71.65%, and 91% (p < 0.001), respectively. Reintubation rates did not differ significantly (p = 0.431).
Conclusion
Among patients at low or intermediate risk for extubation failure with planned HFNC, combining aggressive screening with preventive PEEP and a conservative SBT reduced the time to extubation without increasing the reintubation rate.
ObjectiveThis study assesses the effectiveness of different interventions of knowledge transfer and behaviour modification to improve type 2 diabetes mellitus patients’ (T2DM) reported outcomes ...measures (PROMs) in the long-term. Design: open, community-based pragmatic, multicentre, controlled trial with random allocation by clusters to usual care (UC) or to one of the three interventions.ParticipantsA total of 2334 patients with uncomplicated T2DM and 211 healthcare professionals were included of 32 primary care centres.SettingPrimary Care Centers in Canary Islands (Spain).InterventionThe intervention for patients (PTI) included an educational group programme, logs and a web-based platform for monitoring and automated short message service (SMS). The intervention for professionals (PFI) included an educational programme, a decision support tool embedded into the electronic clinical record and periodic feedback about patients’ results. A third group received both PTI and PFI (combined intervention, CBI).Outcome measureCognitive-attitudinal, behavioural, affective and health-related quality of life (HQoL) variables.ResultsCompared with UC at 24 months, the PTI group significantly improved knowledge (p=0.005), self-empowerment (p=0.002), adherence to dietary recommendations (p<0.001) and distress (p=0.01). The PFI group improved at 24 months in distress (p=0.03) and at 12 months there were improvements in depression (p=0.003), anxiety (p=0.05), HQoL (p=0.005) and self-empowerment (p<0.001). The CBI group improved at 24 months in self-empowerment (p=0.008) and adherence to dietary recommendations (p=0.004) and at 12 months in knowledge (p=0.008), depression (p=0.006), anxiety (p=0.003), distress (p=0.01), HQoL (p<0.001) and neuropathic symptoms (p=0.02). Statistically significant improvements were also observed at 24 months in the proportion of patients who quit smoking for PTI and CBI (41.5% in PTI and 42.3% in CBI vs 21.2% in the UC group).ConclusionsAssessed interventions to improve PROMs in T2DM attain effectiveness for knowledge, self-empowerment, distress, diet adherence and tobacco cessation. PTI produced the most lasting benefits.Trial registration numberClinicalTrials.gov NCT01657227 (6 August 2012) https://clinicaltrials.gov/ct2/show/NCT01657227.
Data from a variety of research programmes are increasingly used by policy makers, researchers, and private sectors to make data-driven decisions related to climate change and variability. Climate ...services are emerging as the link to narrow the gap between climate science and downstream users. The Global Framework for Climate Services (GFCS) of the World Meteorological Organization (WMO) offers an umbrella for the development of climate services and has identified the quality assessment, along with its use in user guidance, as a key aspect of the service provision. This offers an extra stimulus for discussing what type of quality information to focus on and how to present it to downstream users. Quality has become an important keyword for those working on data in both the private and public sectors and significant resources are now devoted to quality management of processes and products. Quality management guarantees reliability and usability of the product served, it is a key element to build trust between consumers and suppliers. Untrustworthy data could lead to a negative economic impact at best and a safety hazard at worst. In a progressive commitment to establish this relation of trust, as well as providing sufficient guidance for users, the Copernicus Climate Change Service (C3S) has made significant investments in the development of an Evaluation and Quality Control (EQC) function. This function offers a homogeneous user-driven service for the quality of the C3S Climate Data Store (CDS). Here we focus on the EQC component targeting the assessment of the CDS datasets, which include satellite and in-situ observations, reanalysis, climate projections, and seasonal forecasts. The EQC function is characterised by a two-tier review system designed to guarantee the quality of the dataset information. While the need of assessing the quality of climate data is well recognised, the methodologies, the metrics, the evaluation framework, and how to present all this information to the users have never been developed before in an operational service, encompassing all the main climate dataset categories. Building the underlying technical solutions poses unprecedented challenges and makes the C3S EQC approach unique. This paper describes the development and the implementation of the operational EQC function providing an overarching quality management service for the whole CDS data.
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