Effect of superficial treatment with new natural antioxidant on salmon (Salmo salar) lipid oxidation

Lipid oxidation is one of the main factors responsible for the quality loss in refrigerated and frozen stored fish products. The aim of the study was to evaluate the effect of superficial treatment of Atlantic salmon (Salmo salar) with dihydroquercetin (DHQ) solutions on the hydrolytic and oxidative changes in fish lipids during refrigerated storage. It was found that treatment with DHQ solution (1.0 g l−1) reduced approximately twice the free fatty acids content of chilled stored salmon. After 11 days of storage at 1 °С, the contents of hydroperoxides (HPO) and 2-thiobarbituric acid reactive substances (TBARS) of these samples decreased with 45.00 and 0.91 mg MDA/kg, respectively. The share of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) in control and experimental samples did not differ significantly (P>0.05). Results obtained show that the superficial treatment of salmon with DHQ solution (1.0 g l−1) delayed the hydrolytic and oxidative changes in fish lipids significantly, thus preserving the salmon freshness up to 11 days of storage at 1 °С

Section on Prospects for Dark Matter Detection of the White Paper on the Status and Future of Ground-Based TeV Gamma-Ray Astronomy

This is a report on the findings of the dark matter science working group for the white paper on the status and future of TeV gamma-ray astronomy. The white paper was commissioned by the American Physical Society, and the full white paper can be found on astro-ph (arXiv:0810.0444). This detailed section discusses the prospects for dark matter detection with future gamma-ray experiments, and the complementarity of gamma-ray measurements with other indirect, direct or accelerator-based searches. We conclude that any comprehensive search for dark matter should include gamma-ray observations, both to identify the dark matter particle (through the charac- teristics of the gamma-ray spectrum) and to measure the distribution of dark matter in galactic halos.Comment: Report from the Dark Matter Science Working group of the APS commissioned White paper on ground-based TeV gamma ray astronomy (19 pages, 9 figures

Cylindrical equilibrium shapes of fluid membranes

Within the framework of the well-known curvature models, a fluid lipid bilayer membrane is regarded as a surface embedded in the three-dimensional Euclidean space whose equilibrium shapes are described in terms of its mean and Gaussian curvatures by the so-called membrane shape equation. In the present paper, all solutions to this equation determining cylindrical membrane shapes are found and presented, together with the expressions for the corresponding position vectors, in explicit analytic form. The necessary and sufficient conditions for such a surface to be closed are derived and several sufficient conditions for its directrix to be simple or self-intersecting are given.Comment: 17 pages, 4 figures. Published in J. Phys. A: Math. Theore

Squeezed between shells? On the origin of the Lupus I molecular cloud. - II. APEX CO and GASS HI observations

Accepted for publication in a future issue of Astronomy & Astrophysics. Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.Context. The Lupus I cloud is found between the Upper-Scorpius (USco) and the Upper-Centaurus-Lupus (UCL) sub-groups of the Scorpius-Centaurus OB-association, where the expanding USco H I shell appears to interact with a bubble currently driven by the winds of the remaining B-stars of UCL. Aims. We investigate if the Lupus I molecular could have formed in a colliding flow, and in particular, how the kinematics of the cloud might have been influenced by the larger scale gas dynamics. Methods. We performed APEX 13CO(2–1) and C 18O(2–1) line observations of three distinct parts of Lupus I that provide kinematic information on the cloud at high angular and spectral resolution. We compare those results to the atomic hydrogen data from the GASS H i survey and our dust emission results presented in the previous paper. Based on the velocity information, we present a geometric model for the interaction zone between the USco shell and the UCL wind bubble. Results. We present evidence that the molecular gas of Lupus I is tightly linked to the atomic material of the USco shell. The CO emission in Lupus I is found mainly at velocities between vLSR = 3–6 km s−1 which is in the same range as the H i velocities. Thus, the molecular cloud is co-moving with the expanding USco atomic H i shell. The gas in the cloud shows a complex kinematic structure with several line-of-sight components that overlay each other. The non-thermal velocity dispersion is in the transonic regime in all parts of the cloud and could be injected by external compression. Our observations and the derived geometric model agree with a scenario where Lupus I is located in the interaction zone between the USco shell and the UCL wind bubble. Conclusions. The kinematics observations are consistent with a scenario where the Lupus I cloud formed via shell instabilities. The particular location of Lupus I between USco and UCL suggests that counter-pressure from the UCL wind bubble and pre-existing density enhancements, perhaps left over from the gas stream that formed the stellar subgroups, may have played a role in its formation.Peer reviewedFinal Accepted Versio

Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors

Strategies to induce p53 activation in wtp53-retaining tumors carry high potential in cancer therapy. Nutlin, a potent highly selective MDM2 inhibitor, induces non-genotoxic p53 activation. Although Nutlin shows promise in promoting cell death in hematopoietic malignancies, a major roadblock is that most solid cancers do not undergo apoptosis but merely reversible growth arrest. p53 inhibition by unopposed MDMX is one major cause for apoptosis resistance to Nutlin. The Hsp90 chaperone is ubiquitously activated in cancer cells and supports oncogenic survival pathways, many of which antagonize p53. The Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG) is known to induce p53-dependent apoptosis. We show here that in multiple difficult-to-kill solid tumor cells 17AAG modulates several critical components that synergize with Nutlin-activated p53 signaling to convert Nutlin's transient cytostatic response into a cytotoxic killing response in vitro and in xenografts. Combined with Nutlin, 17AAG destabilizes MDMX, reduces MDM2, induces PUMA and inhibits oncogenic survival pathways, such as PI3K/AKT, which counteract p53 signaling at multiple levels. Mechanistically, 17AAG interferes with the repressive MDMX–p53 axis by inducing robust MDMX degradation, thereby markedly increasing p53 transcription compared with Nutlin alone. To our knowledge Nutlin+17AAG represents the first effective pharmacologic knockdown of MDMX. Our study identifies 17AAG as a promising synthetic lethal partner for a more efficient Nutlin-based therapy

Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

BACKGROUND: The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents. METHODS: In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels. RESULTS: The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275-0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status. CONCLUSIONS: Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease. TRIAL REGISTRATION: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT. CLINICALTRIALS: gov Identifier: NCT05261867

Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry

Aims: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users). Methods: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization. Results: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33–0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21–0.98; p = 0.041). Conclusions: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI. Registration: Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov Identifier: NCT05261867

Drivers of plant diversity in Bulgarian dry grasslands vary across spatial scales and functional-taxonomic groups

Questions: Studying dry grasslands in a previously unexplored region, we asked: (a) which environmental factors drive the diversity patterns in vegetation; (b) are taxonomic groups (vascular plants, bryophytes, lichens) and functional vascular plant groups differently affected; and (c) how is fine-grain beta diversity affected by environmental drivers? Location: Northwestern and Central Bulgaria. Methods: We sampled environmental data and vascular plant, terricolous bryophyte and lichen species in 97 10-m2 plots and 15 nested-plot series with seven grain sizes (0.0001–100 m2) of ten grassland sites within the two regions. We used species richness as measure of alpha-diversity and the z-value of the power-law species–area relationship as measure of beta-diversity. We analysed effects of landscape, topographic, soil and land-use variables on the species richness of the different taxonomic and functional groups. We applied generalised linear models (GLMs) or, in the presence of spatial autocorrelation, generalised linear mixed-effect models (GLMMs) in a multi-model inference framework. Results: The main factors affecting total and vascular plant species richness in 10-m2 plots were soil pH (unimodal) and inclination (negative). Species richness of bryophytes was positively affected by rock cover, sand proportion and negatively by inclination. Inclination and litter cover were also negative predictors of lichen species richness. Elevation negatively affected phanerophyte and therophyte richness, but positively that of cryptophytes. A major part of unexplained variance in species richness was associated with the grassland site. The z-values for total richness showed a positive relationship with elevation and inclination. Conclusions: Environmental factors shaping richness patterns strongly differed among taxonomic groups, functional vascular plant groups and spatial scales. The disparities between our and previous findings suggest that many drivers of biodiversity cannot be generalised but rather depend on the regional context. The large unexplained variance at the site level calls for considering more site-related factors such as land-use history

MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

<p>Abstract</p> <p>Background</p> <p>Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified <it>MDM2 </it>gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy.</p> <p>Methods</p> <p>A panel of sarcoma cell lines with different <it>TP53 </it>and <it>MDM2 </it>status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined.</p> <p>Results</p> <p>Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type <it>TP53 </it>and amplified <it>MDM2</it>, or with Methotrexate in both <it>MDM2 </it>normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated <it>TP53</it>, but inhibited the effect of Methotrexate.</p> <p>Conclusion</p> <p>The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.</p

The Contribution of Social Networks to the Health and Self-Management of Patients with Long-Term Conditions: A Longitudinal Study

Evidence for the effectiveness of patient education programmes in changing individual self-management behaviour is equivocal. More distal elements of personal social relationships and the availability of social capital at the community level may be key to the mobilisation of resources needed for long-term condition self-management to be effective. Aim: To determine how the social networks of people with long-term conditions (diabetes and heart disease) are associated with health-related outcomes and changes in outcomes over time. Methods: Patients with chronic heart disease (CHD) or diabetes (n = 300) randomly selected from the disease registers of 19 GP practices in the North West of England. Data on personal social networks collected using a postal questionnaire, alongside face-to-face interviewing. Follow-up at 12 months via postal questionnaire using a self-report grid for network members identified at baseline. Analysis: Multiple regression analysis of relationships between health status, self-management and health economics outcomes, and characteristics of patients’ social networks. Results: Findings indicated that: (1) social involvement with a wider variety of people and groups supports personal self-management and physical and mental well-being; (2) support work undertaken by personal networks expands in accordance with health needs helping people to cope with their condition; (3) network support substitutes for formal care and can produce substantial saving in traditional health service utilisation costs. Health service costs were significantly (p0.01) reduced for patients receiving greater levels of illness work through their networks. Conclusions: Support for self-management which achieves desirable policy outcomes should be construed less as an individualised set of actions and behaviour and more as a social network phenomenon. This study shows the need for a greater focus on harnessing and sustaining the capacity of networks and the importance of social involvement with community groups and resources for producing a more desirable and cost-effective way of supporting long term illness management