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Objective: Previous gestational diabetes (GDM) is associated with a significant lifetime risk of type 2 diabetes. In this study, we assessed the performance of HbA1c and fasting plasma glucose (FPG) measurements against that of 75 g oral glucose tolerance testing (OGTT) for the follow-up screening of women with previous GDM. Methods: Two hundred and sixty-six women with previous GDM underwent the follow-up testing (mean of 2.6 years (S.D. 1.0) post-index pregnancy) using HbA1c (100%), and 75 g OGTT (89%) or FPG (11%). American Diabetes Association (ADA) criteria for abnormal glucose tolerance were used. Design, cohort study, and results: The ADA HbA1c high-risk cut-off of 39 mmol/mol yielded sensitivity of 45% (95% CI 32, 59), specificity of 84% (95% CI 78, 88), negative predictive value (NPV) of 87% (95% CI 82, 91) and positive predictive value (PPV) of 39% (95% CI 27, 52) for detecting abnormal glucose tolerance. ADA high-risk criterion for FPG of 5.6 mmol/l showed sensitivity of 80% (95% CI 66, 89), specificity of 100% (95% CI 98, 100), NPV of 96% (95% CI 92, 98) and PPV of 100% (95% CI 91, 100). Combining HbA1c >39 mmol/mol with FPG >5.6 mmol/l yielded sensitivity of 90% (95% CI 78, 96), specificity of 84% (95% CI 78, 88), NPV of 97% (95% CI 94, 99) and PPV of 56% (95% CI 45, 66). Conclusions: Combining test cut-offs of 5.6 mmol/l and HbA1c 39 mmol/mol identifies 90% of women with abnormal glucose tolerance post-GDM (mean 2.6 years (S.D.1.0) post-index pregnancy). Applying this follow-up strategy will reduce the number of OGTT tests required by 70%, will be more convenient for women and their practitioners, and is likely to lead to increased uptake of long-term retesting by these women whose risk for type 2 diabetes is substantially increased. [ABSTRACT FROM AUTHOR]

Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways to enter the brain (the "gateway" hypothesis) and the potential feedback loop by which sensory function may be impacted by central nervous system infection. We emphasize detection of sensory changes as first-line surveillance in senior adults to identify and remove potential insults, like microbial infections, that could precipitate brain pathology., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sirtuin isoform 2 (SIRT2) is an enzyme that catalyzes the removal of acyl groups from lysine residues. SIRT2's catalytic domain has a hydrophobic tunnel where its substrate acyl groups bind. Here, we report that the fluorescent probe 1-aminoanthracene (AMA) binds within SIRT2's hydrophobic tunnel in a substrate-dependent manner. AMA's interaction with SIRT2 was characterized by its enhanced fluorescence upon protein binding (>10-fold). AMA interacted weakly with SIRT2 alone in solution ( K d = 37 μM). However, when SIRT2 was equilibrated with a decanoylated peptide substrate, AMA's affinity for SIRT2 was enhanced ∼10-fold ( K d = 4 μM). The peptide's decanoyl chain and AMA co-occupied SIRT2's hydrophobic tunnel when bound to the protein. In contrast, binding of AMA to SIRT2 was competitive with a myristoylated substrate whose longer acyl chain occluded the entire tunnel. AMA competitively inhibited SIRT2 demyristoylase activity with an IC 50 of 21 μM, which was significantly more potent than its inhibition of other deacylase activities. Finally, binding and structural analysis suggests that the AMA binding site in SIRT2's hydrophobic tunnel was structurally stabilized when SIRT2 interacted with a decanoylated or 4-oxononanoylated substrate, but AMA's binding site was less stable when SIRT2 was bound to an acetylated substrate. Our use of AMA to explore changes in SIRT2's hydrophobic tunnel that are induced by interactions with specific acylated substrates has implications for developing ligands that modulate SIRT2's substrate specificity.

While Gram-positive organisms are the most common causative agent of initial bone infections, the percentage of Gram-negative species increases in reoccurring bone infections. As bacterial internalization has been suggested as one cause of reoccurring bone infection, we tested the hypothesis that Gram-negative species of bacteria can be internalized into bone cells. Using the MLO-A5 and the MLO-Y4 cell lines as our cell models, we demonstrated that the Gram-negative species, Proteus mirabilis and Serratia marcescens, can be internalized in these cells using an internalization assay. This rate at which these two species were internalized was both time- and initial concentration-dependent. Confocal analysis demonstrated the presence of internalized bacteria within both cell types. Inhibition of the cellular uptake with methyl-β-cyclodextrin and chloroquine both reduced internalized bacteria, indicating that this process is, at least in part, cell mediated. Finally, we demonstrated that the presence of internalized P. mirabilis did not impact cell viability, measured either by lactate dehydrogenase (LDH) release or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) activity, while the presence of S. marcescens, on the other hand, both increased LDH release and reduced MTT activity, indicating a loss of cell viability in response to the organism. These results indicated that both species of Gram-negative bacteria can be internalized by bone cells and that these internalized bacteria could potentially result in reoccurring bone infections. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:861-870, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Purpose: Posterior capsule opacification (PCO) is a vision-impairing disease that occurs in some adults and most children after cataract surgery. Contractile myofibroblasts contribute to PCO by producing wrinkles in the lens capsule that scatter light. Myofibroblasts in the lens originate from Myo/Nog cells named for their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study we tested the effects of depleting Myo/Nog cells on development of PCO., Methods: Myo/Nog cells were eliminated by injecting the G8 antibody conjugated to 3DNA nanocarriers for the cytotoxin doxorubicin (G8:3DNA:Dox) during cataract surgery in rabbits. The severity of PCO was scored by slit lamp analysis, gross and histologic observation, and immunofluorescence localization of α-smooth muscle actin., Results: G8:3DNA:Dox specifically induced cell death in Myo/Nog cells in the lens. None of the lenses administered G8:3DNA containing 9 to 36 μM doxorubicin developed greater than trace levels of central PCO and few myofibroblasts were present on the capsule. Less than 9% of these lenses exhibited greater than mild levels of peripheral PCO. Doxorubucin itself reduced PCO; however, myofibroblasts and wrinkles were abundant in the lens, and off-target effects were observed in the ciliary processes and cornea., Conclusions: Myo/Nog cells are the primary source of myofibroblasts in the lens after cataract surgery. Targeted depletion of Myo/Nog cells has potential for preventing PCO and preserving vision.

Myo/Nog cells are identified by their expression of the skeletal muscle specific transcription factor MyoD and the bone morphogenetic protein inhibitor noggin, and binding of the G8 monoclonal antibody. Their release of noggin is critical for morphogenesis and skeletal myogenesis. In the adult, Myo/Nog cells are present in normal tissues, wounds and skin tumors. Myo/Nog cells in the lens give rise to myofibroblasts that synthesize skeletal muscle proteins. The purpose of this study was to screen human lens tissue, rhabdomyosarcoma cell lines, and tissue sections from rhabdomyosarcoma, Wilms and tumors lacking features of skeletal muscle for co-localization of antibodies to Myo/Nog cell markers and the lens beaded filament proteins filensin and CP49. Immunofluorescence localization experiments revealed that Myo/Nog cells of the lens bind antibodies to beaded filament proteins. Co-localization of antibodies to G8, noggin, filensin and CP49 was observed in most RC13 and a subpopulation of RD human rhabdomyosarcoma cell lines. Western blotting with beaded filament antibodies revealed bands of similar molecular weights in RC13 and murine lens cells. Human alveolar, embryonal, pleomorphic and spindle cell rhabdomyosarcomas and Wilms tumors contained a subpopulation of cells immunoreactive for G8, noggin, MyoD and beaded filaments. G8 was also co-localized with filensin mRNA. Staining for beaded filament proteins was not detected in G8 positive cells in leiomyosarcomas, squamous and basal cell carcinomas, syringocarciomas and malignant melanomas. Lens beaded filament proteins were thought to be present only in the lens. Myo/Nog-like cells immunoreactive for beaded filaments may be diagnostic of tumors related to the skeletal muscle lineage., Competing Interests: The authors have declared that no competing interests exist.

Background: Although violence against women (VAW) is a global public health issue, its importance as a health issue is often unrecognized in legal and health policy documents. This paper uses Sri Lanka as a case study to explore the factors influencing the national policy response to VAW, particularly by the health sector., Methods: A document based health policy analysis was conducted to examine current policy responses to VAW in Sri Lanka using the Shiffman and Smith (2007) policy analysis framework., Results: The findings suggest that the networks and influences of various actors in Sri Lanka, and their ideas used to frame the issue of VAW, have been particularly important in shaping the nature of the policy response to date. The Ministry of Women and Child Affairs led the national response on VAW, but suffered from limited financial and political support. Results also suggest that there was low engagement by the health sector in the initial policy response to VAW in Sri Lanka, which focused primarily on criminal legislation, following global influences. Furthermore, a lack of empirical data on VAW has impeded its promotion as a health policy issue, despite financial support from international organisations enabling an initial health systems response by the Ministry of Health. Until a legal framework was established (2005), the political context provided limited opportunities for VAW to also be construed as a health issue. It was only then that the Ministry of Health got legitimacy to institutionalise VAW services., Conclusion: Nearly a decade later, a change in government has led to a new national plan on VAW, giving a clear role to the health sector in the fight against VAW. High-level political will, criminalisation of violence, coalesced women's groups advocating for legislative change, prevalence data, and financial support from influential institutions are all critical elements helping frame violence as a national public health issue.