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The article describes the case of alkaline ketoalkalosis and ketoacidosis in six type 1 diabetes patients including an intensive care unit admission for vomiting, coughing and general weakness complicated by pneumonia. A second case had complications of nephropathy and retinopathy for hyperglycemia while the next one had gastroparesis treated with gastric electric stimulation. The other cases involved fasting with only water and Duchenne muscular dystrophy with home respiratory aid.

Systemic administration of beta‐hydroxybutyrate (BHB) decreases whole‐body protein oxidation and muscle protein breakdown in humans. We aimed to determine any direct effect of BHB on skeletal muscle protein turnover when administered locally in the femoral artery. Paired design with each subject being investigated on one single occasion with one leg being infused with BHB and the opposing leg acting as a control. We studied 10 healthy male volunteers once with bilateral femoral vein and artery catheters. One artery was perfused with saline (Placebo) and one with sodium‐BHB. Labelled phenylalanine and palmitate were used to assess local leg fluxes. Femoral vein concentrations of BHB were significantly higher in the intervention leg (3.4 (3.2, 3.6) mM) compared with the placebo‐controlled leg (1.9 (1.8, 2.1) mM) with a peak difference of 1.4 (1.1, 1.7) mM, p < 0.0005. Net loss of phenylalanine for BHB vs Placebo −6.7(−10.8, −2.7) nmol/min vs −8.7(−13.8, −3.7) nmol/min, p = 0.52. Palmitate flux and arterio‐venous difference of glucose did not differ between legs. Under these experimental conditions, we failed to observe the direct effects of BHB on skeletal muscle protein turnover. This may relate to a combination of high concentrations of BHB (close to 2 mM) imposed systemically by spillover leading to high BHB concentrations in the saline‐infused leg and a lack of major differences in concentration gradients between the two sides—implying that observations were made on the upper part of the dose–response curve for BHB and the relatively small number of subjects studied. [ABSTRACT FROM AUTHOR]

Introduction: The lack of a cross-sectorial overview of patients hampers the delivery of integrated care. Care providers lack an easy accessible overview capable of visualizing data from all care providers who jointly contribute to the care of a patient. To digitally connect care providers, Steno Diabetes Center Aarhus, Denmark, leads a project group developing a IT-solution named 'SAMBLIK' (translatable to 'viewing exactly the same'). SAMBLIK is data-driven, shares relevant diabetes data across the national IT infrastructure (hospitals, general practice and municipality) and displays data points that capture the complete pathway of a person living with diabetes (e.g., out-patient visits, diagnostic tests). Aim and Method: SAMBLIK is being pilot tested (December 2021-January 2022) in two Danish administrative regions and within a care cluster (a hospital, nearby municipalities and general practices) in each. The aim of this pilot test is to evaluate the user experience and implementation of SAMBLIK. Data is collected using semi-structured interviews (n=30) and observations. Data collection is informed by insights from the Technology Acceptance Model and Relational Coordination Model. Respondents include endocrinologists and nurses (hospital), general practitioners and practice staff (general practice), home nurses and staff working with health promotion (municipality). Data collection takes place in January and February 2022. Highlights: Expected benefits of SAMBLIK: provides a diabetes relevant and identical overview of patient history across sectors and IT-platforms; visualizes patient data and patient treatment goals across sectors; combines national and local data sources ensuring data completeness; integrates into the existing local IT-systems that practitioners use in general practices; provides a data foundation for care providers to improve care and to improve knowledge sharing and communication across sectors. These benefits will in turn ensure that patients are not de facto responsible for ""carrying"" their data across sectors. SAMBLIK is module-based and thus possible to extend to other diseases. Lessons learned: address a need of high practical importance to practitioners; get key stakeholders engaged early in the development process; make data the driver of the collaboration; and integrate the IT-solution into existing IT-systems; keep it simple. Conclusion: The IT-solution, SAMBLIK, is expected to have high practical importance for practitioners working in different health care sectors because it provides a historically overview of relevant data for diabetes care. SAMBLIK combines disease-specific data sources from the national and local infrastructure, which ensures data completeness and enables efficient, low-cost upscaling. Implications: SAMBLIK helps solving a pressing need for sharing data and providing data-driven care. Being a generic IT-solution premised on the idea of modularity allows SAMBLIK to be scaled into other patient groups and to other administrative regions. The learning points from the pilot test and evaluation will further aid transferability. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence suggests that exercise training has beneficial effects in cancer patients. The aim of the present study was to investigate the molecular basis underlying these beneficial effects in skeletal muscle from cancer patients. Methods: We investigated expression of selected proteins involved in cellular processes known to orchestrate adaptation to exercise training by western blot. Skeletal muscle biopsies were sampled from ten cancer patients before and after 4–7 weeks of ongoing chemotherapy, and subsequently after 10 weeks of continued chemotherapy in combination with exercise training. Biopsies from ten healthy matched subjects served as reference. Results: The expression of the insulin-regulated glucose transporter, GLUT4, increased during chemotherapy and continued to increase during exercise training. A similar trend was observed for ACC, a key enzyme in the biosynthesis and oxidation of fatty acids, but we did not observe any changes in other regulators of substrate metabolism (AMPK and PDH) or mitochondrial proteins (Cyt-C, COX-IV, SDHA, and VDAC). Markers of proteasomal proteolysis (MURF1 and ATROGIN-1) decreased during chemotherapy, but did not change further during chemotherapy combined with exercise training. A similar pattern was observed for autophagy-related proteins such as ATG5, p62, and pULK1 Ser757, but not ULK1 and LC3BII/LC3BI. Phosphorylation of FOXO3a at Ser318/321 did not change during chemotherapy, but decreased during exercise training. This could suggest that FOXO3a-mediated transcriptional regulation of MURF1 and ATROGIN-1 serves as a mechanism by which exercise training maintains proteolytic systems in skeletal muscle in cancer patients. Phosphorylation of proteins that regulate protein synthesis (mTOR at Ser2448 and 4EBP1 at Thr37/46) increased during chemotherapy and leveled off during exercise training. Finally, chemotherapy tended to increase the number of satellite cells in type 1 fibers, without any further change during chemotherapy and exercise training. Conversely, the number of satellite cells in type 2 fibers did not change during chemotherapy, but increased during chemotherapy combined with exercise training. Conclusions: Molecular signaling cascades involved in exercise training are disturbed during cancer and chemotherapy, and exercise training may prevent further disruption of these pathways. Trial registration: The study was approved by the local Scientific Ethics Committee of the Central Denmark Region (Project ID: M-2014-15-14; date of approval: 01/27/2014) and the Danish Data Protection Agency (case number 2007-58-0010; date of approval: 01/28/2015). The trial was registered at http//www.clinicaltrials.gov (registration number: NCT02192216; date of registration 07/17-2014). [ABSTRACT FROM AUTHOR]

In this study we used an AFM to investigate the cytoskeletal properties of live Dictyostelium discoideumcells by measuring the local stiffness across individual living cells. We have examined differences in elastic properties of polarized and unpolarized AX3 wild type and the mutant DAip1-cells, as well as the differences in the front and rear of the cells in relation to organization of the actin cytoskeleton. We found that the average Young's modulus increases upon polarization for the thin regions of the cell and that in polarized cells, the cell front was stiffer than the cell back. We also found that AX3 cells were stiffer than DAip1-cells. This finding suggests that actin polymerization is one of the major determinants of cell motility in Dictyostelium. In addition, a thin agarose film was studied as a model system to examine the influence of the substrate of thin materials probed with the AFM. [ABSTRACT FROM AUTHOR]

In Spring 2011, the Lick AGN Monitoring Project observed a sample of 15 bright, nearby Seyfert 1 galaxies in the V band as part of a reverberation mapping campaign. The observations were taken at six ground-based telescopes, including the West Mountain Observatory 0.91 m telescope, the 0.76 m Katzman Automatic Imaging Telescope, 0.6 m Super-LOTIS at Kitt Peak, the Palomar 60 inch telescope, and the 2 m Faulkes telescopes North and South. The V-band light curves measure the continuum variability of our sample of Seyferts on an almost daily cadence for 2–3 months. We use image-subtraction software to isolate the variability of the Seyfert nucleus from the constant V-band flux of the host galaxy for the most promising targets, and we adopt standard aperture photometry techniques for the targets with smaller levels of variability. These V-band light curves will be used, with measurements of the broad emission line flux, to measure supermassive black hole masses and to constrain the geometry and dynamics of the broad-line region through dynamical modeling techniques. [ABSTRACT FROM AUTHOR]

Summary The α-oxoaldehyde methylglyoxal is a ubiquitous and highly reactive metabolite known to be involved in aging- and diabetes-related diseases. If not detoxified by the endogenous glyoxalase system, it exerts its detrimental effects primarily by reacting with biopolymers such as DNA and proteins. We now demonstrate that during ketosis, another metabolic route is operative via direct non-enzymatic aldol reaction between methylglyoxal and the ketone body acetoacetate, leading to 3-hydroxyhexane-2,5-dione. This novel metabolite is present at a concentration of 10%–20% of the methylglyoxal level in the blood of insulin-starved patients. By employing a metabolite-alkyne-tagging strategy it is clarified that 3-hydroxyhexane-2,5-dione is further metabolized to non-glycating species in human blood. The discovery represents a new direction within non-enzymatic metabolism and within the use of alkyne-tagging for metabolism studies and it revitalizes acetoacetate as a competent endogenous carbon nucleophile. [ABSTRACT FROM AUTHOR]

Self-organization is a promising method within the framework of bottom-up architectures to generate nanostructures in an efficient way. The present work demonstrates that self-organization on the length scale of a few to several tens of nanometers can be achieved by a proper combination of a large (organic) molecule and a vicinal metal surface if the local bonding of the molecule on steps is significantly stronger than that on low-index surfaces. In this case thermal annealing may lead to large mass transport of the subjacent substrate atoms such that nanometer-wide and micrometer-long molecular stripes or other patterns are being formed on high-index planes. The formation of these patterns can be controlled by the initial surface orientation and adsorbate coverage. The patterns arrange self-organized in regular arrays by repulsive mechanical interactions over long distances accompanied by a significant enhancement of surface stress. We demonstrate this effect using the planar organic molecule PTCDA as adsorbate and Ag(10 8 7) and Ag(775) surfaces as substrate. The patterns are directly observed by STM, the formation of vicinal surfaces is monitored by high-resolution electron diffraction, the microscopic surface morphology changes are followed by spectro-microscopy, and the macroscopic changes of surface stress are measured by a cantilever bending method. The in situ combination of these complementary techniques provides compelling evidence for elastic interaction and a significant stress contribution to long-range order and nanopattern formation. [ABSTRACT FROM AUTHOR]

Background and Aims The aim of this work was the identification and molecular characterization of novel sugar beet (Beta vulgaris) repetitive sequences to unravel the impact of repetitive DNA on size and evolution of Beta genomes via amplification and diversification. Methods Genomic DNA and a pool of B. vulgaris repetitive sequences were separately used as probes for a screening of high-density filters from a B. vulgaris plasmid library. Novel repetitive motifs were identified by sequencing and further used as probes for Southern analyses in the genus Beta. Chromosomal localization of the repeats was analysed by fluorescent in situ hybridization on chromosomes of B. vulgaris and two other species of the section Beta. Key Results Two dispersed repetitive families pDvul1 and pDvul2 and the tandemly arranged repeat family pRv1 were isolated from a sugar beet plasmid library. The dispersed repetitive families pDvul1 and pDvul2 were identified in all four sections of the genus Beta. The members of the pDvul1 and pDvul2 family are scattered over all B. vulgaris chromosomes, although amplified to a different extent. The pRv1 satellite repeat is exclusively present in species of the section Beta. The centromeric satellite pBV1 by structural variations of the monomer and interspersion of pRv1 units forms complex satellite structures, which are amplified in different degrees on the centromeres of 12 chromosomes of the three species of the Beta section. Conclusions The complexity of the pBV1 satellite family observed in the section Beta of the genus Beta and, in particular, the strong amplification of the pBV1/pRv1 satellite in the domesticated B. vulgaris indicates the dynamics of centromeric satellite evolution during species radiation within the genus. The dispersed repeat families pDvul1 and pDvul2 might represent derivatives of transposable elements. [ABSTRACT FROM AUTHOR]