Objective
To examine the feasibility of continuous glucose monitoring (CGM) use in very young children with type 1 diabetes (T1D).
Research design and methods
Twenty‐three children less than 4 yr of ...age with T1D were provided with a FreeStyle Navigator® (n = 21) or a Paradigm® (n = 2) CGM device. At baseline, mean age was 3.0 ± 0.8 yr, mean hemoglobin A1c (HbA1c) was 8.0 ± 0.8%, 10 were using an insulin pump and 13 were on multiple daily injections. CGM use was evaluated over a 6‐month period.
Results
Three children dropped out of the study before the end of 6 months. Among the 20 children who completed 6 months of follow‐up, CGM use in month 6 was ≥6 d/wk in 9 (45%), 4 ≤ 6 d/wk in 2 (10%), and <4 d/wk in 9 (45%). Skin reactions were minimal. Although there was no detectable change in mean HbA1c between baseline and 6 months (7.9 and 8.0%, respectively), there was a high degree of parental satisfaction with CGM as measured on the CGM satisfaction scale questionnaire. A high percentage of glucose values were in the hyperglycemic range, and biochemical hypoglycemia was infrequent.
Conclusion
More than 40% of very young children were able to safely use CGM on a near‐daily basis after 6 months. CGM demonstrated frequent hyperglycemic excursions, with a large variability in glucose readings. Although improvement in glycemic control was not detected in the group as a whole, parental satisfaction with CGM was high.
Dinitrogen (N2)-fixation by cyanobacteria in symbiosis with feather mosses represents the main pathway of biological N input into boreal forests. Despite its significance, little is known about the ...gene repertoire needed for the establishment and maintenance of the symbiosis. To determine gene acquisitions or regulatory rewiring allowing cyanobacteria to form this symbiosis, we compared closely related Nostoc strains that were either symbiosis-competent or non-competent, using a proteogenomics approach and a unique experimental setup allowing for controlled chemical and physical contact between partners. Thirty-two protein families were only in the genomes of competent strains, including some never before associated with symbiosis. We identified conserved orthologs that were differentially expressed in competent strains, including gene families involved in chemotaxis and motility, NO regulation, sulfate/phosphate transport, sugar metabolism, and glycosyl-modifying and oxidative stress-mediating exoenzymes. In contrast to other cyanobacteria-plant symbioses, the moss-cyanobacteria epiphytic symbiosis is distinct, with the symbiont retaining motility and chemotaxis, and not modulating N-fixation, photosynthesis, GS-GOGAT cycle, and heterocyst formation. Our work expands our knowledge of plant cyanobacterial symbioses, provides an interaction model of this ecologically significant symbiosis, and suggests new currencies, namely nitric oxide and aliphatic sulfonates, may be involved in establishing and maintaining this symbiosis.
23A2 myoblasts expressing GAP-resistant, constitutively active G12V:H-Ras (A2:G12V:H-Ras myoblasts) display a transformed morphology and do not undergo mitogen-deprivation-induced differentiation or ...the associated apoptosis. To determine the phenotype induced by F156L:H-Ras, a constitutively active mutant with enhanced nucleotide exchange activity rather than impaired GAP-stimulated GTPase activity, myoblast cell lines were established that stably express F156L:H-Ras at levels of H-Ras comparable to the A2:G12V:H-Ras myoblasts. These A2:F156L:H-Ras myoblast cell lines do not possess a transformed morphology, and while differentiation and apoptosis are impaired, these processes are not abrogated as in the A2:G12V:H-Ras myoblasts. Surprisingly, while expression of either G12V:H-Ras or F156L:H-Ras results in constitutive signaling through PI3-kinase, only cells expressing G12V:H-Ras additionally possess constitutive signaling through MAPK, and NFκB. Pharmacological abrogation of the Ras-induced constitutive PI3-kinase signal, however, is not responsible for the impaired differentiation or apoptosis in either A2:G12V:H-Ras myoblasts or A2:F156L:H-Ras myoblasts. Thus, our data suggest that a pathway distinct from those that signals through MAPK, NFκB or PI3-kinase is responsible for the impaired differentiation and apoptosis in 23A2 skeletal myoblasts expressing constitutively active Ras.
Phospholipases A2 (PLA2) are potent regulators of the inflammatory response. We have observed that Group IV cPLA2 activity is required for the production of superoxide anion (O2-) in human monocytes ...Li Q., Cathcart M.K. J. Biol. Chem. 272 (4) (1997) 2404-2411.. We have previously identified PKC alpha as a kinase pathway required for monocyte O2- production Li Q., Cathcart M.K. J. Biol. Chem. 269 (26) (1994) 17508-17515.. We therefore investigated the potential interaction between PKC alpha and cPLA2 by evaluating the requirement for specific PKC isoenzymes in the process of activating cPLA2 enzymatic activity and protein phosphorylation upon monocyte activation. We first showed that general PKC inhibitors and antisense oligodeoxyribonucleotides (ODN) to the cPKC group of PKC enzymes inhibited cPLA2 activity. To distinguish between PKC alpha and PKC beta isoenzymes in regulating cPLA2 protein phosphorylation and enzymatic activity, we employed our previously characterized PKC alpha or PKC beta isoenzyme-specific antisense ODN Li Q., Subbulakshmi V., Fields A.P., Murray, N.R., Cathcart M.K., J. Biol. Chem. 274 (6) (1999) 3764-3771. Suppression of PKC alpha expression, but not PKC beta expression, inhibited cPLA2 protein phosphorylation and enzymatic activity. Additional studies ruled out a contribution by Erk1/2 to cPLA2 phosphorylation and activation. We also found that cPLA2 co-immunoprecipitated with PKC alpha and vice versa. In vitro studies demonstrated that PKC alpha could directly phosphorylate cPLA2.and enhance enzymatic activity. Finally, we showed that addition of arachidonic acid restored the production of O2- in monocytes defective in either PKC alpha or cPLA2 expression. Taken together, our data suggest that PKC alpha , but not PKC beta , is the predominant cPKC isoenzyme required for cPLA2 protein phosphorylation and maximal induction of cPLA2 enzymatic activity upon activation of human monocytes. Our data also support the concept that the requirements for PKC alpha and cPLA2 in O2- generation are solely due to their seminal role in generating arachidonic acid.
The sensitivities of contrast medium-enhanced computed tomography (CT), delayed CT (DCT), CT during arterial portography (CTAP), and magnetic resonance (MR) imaging for detecting focal liver lesions ...were prospectively evaluated in eight patients who subsequently underwent hepatic lobectomy or transplantation. Pathologic evaluation of the resected liver specimens demonstrated 37 lesions. The sensitivities were 81% (30 of 37 lesions) for CTAP, 57% (21 of 37 lesions) for MR imaging, 52% (12 of 23 lesions) for DCT, and 38% (14 of 37 lesions) for contrast-enhanced CT. The difference between the sensitivity of CTAP and the sensitivities of the other imaging tests was statistically significant (P less than .004). Of the lesions smaller than 1 cm in diameter, CTAP depicted 61% (11 of 18 lesions), MR imaging 17% (three of 18 lesions), CT 0% (zero of 18 lesions), and DCT 0% (zero of nine lesions). It is concluded that for preoperative detection of focal hepatic masses, CTAP is the most accurate technique available to most radiologists. Patients with primary or secondary hepatic neoplasms who are being considered for hepatic resection should undergo CTAP as part of their preoperative examination.
Summary
Diatoms are unicellular photosynthetic algae with promise for green production of fuels and other chemicals. Recent genome‐editing techniques have greatly improved the potential of many ...eukaryotic genetic systems, including diatoms, to enable knowledge‐based studies and bioengineering. Using a new technique, transcription activator‐like effector nucleases (
TALEN
s), the gene encoding the urease enzyme in the model diatom,
Phaeodactylum tricornutum
, was targeted for interruption. The knockout cassette was identified within the urease gene by
PCR
and Southern blot analyses of genomic
DNA
. The lack of urease protein was confirmed by Western blot analyses in mutant cell lines that were unable to grow on urea as the sole nitrogen source. Untargeted metabolomic analysis revealed a build‐up of urea, arginine and ornithine in the urease knockout lines. All three intermediate metabolites are upstream of the urease reaction within the urea cycle, suggesting a disruption of the cycle despite urea production. Numerous high carbon metabolites were enriched in the mutant, implying a breakdown of cellular C and N repartitioning. The presented method improves the molecular toolkit for diatoms and clarifies the role of urease in the urea cycle.
We demonstrate that during 23A2 skeletal myoblast differentiation, between 30-35% of the population apoptose. Both differentiation and apoptosis are controlled by the variables of cell density and ...time and these variables are inversely related. In response to conditions that permit both differentiation and apoptosis of parental 23A2 myoblasts, myoblasts rendered differentiation-defective by constitutive Ras signaling (A2:H-Ras myoblasts) do not apoptose. This is not merely a consequence of their differentiation-defective phenotype since myoblasts rendered differentiation-defective by expression of E1A (A2:E1A myoblasts) still apoptose. Although signaling through MEK is important to the survival of proliferating parental 23A2 myoblasts, constitutive signaling through MEK is not responsible for the survival of A2:H-Ras myoblasts. Finally, we demonstrate that caspase 3 is activated and that pharmacological inhibition of caspase 3 activity delays apoptosis without affecting differentiation. Abrogating apoptosis without affecting differentiation could be a useful approach to improve the efficacy of myoblast transfer in the treatment of muscular dystrophies.
Purpose - The purpose of this paper is to discuss contemporary approaches to workplace health and well-being, articulating key differences in the intervention architecture between public and ...workplace health contexts and implications for intervention design.Design methodology approach - Contemporary practice is discussed in light of calls for a paradigm shift in occupational health from a treatment orientation to an holistic approach focused on mitigation of the causes of ill health and the promotion of well-being. In practice, relatively few organizations have or seem able to engage with a broader perspective that encompasses challenges to health and well-being associated with contextual organizational drivers, e.g. job design role, workload, systems of reward, leadership style and the underpinning climate. Drawing upon insights from public health and the workplace safety tradition, the scope for broadening the perspective on intervention (in terms of vectors of harm addressed, theory of change and intervention logic) is discussed.Findings - There are important differences in scope and options for intervention between public health and workplace health contexts. While there is scope to emulate public health practice, this should not constrain thinking over intervention opinions. Increased awareness of these key differences within work organizations, and an evidence-based epidemiological approach to learning has the potential to strengthen and broaden the approach to workplace health and well-being management.Originality value - The authors argue that approaches to workplace well-being interventions that selectively cross-fertilise and adapt elements of public health interventions offer promise for realising a broader change agenda and for building inherently healthy workplaces.
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