Role of parathyroid hormone in regeneration of irradiated bone in a murine model of mandibular distraction osteogenesis

BackgroundThe purpose of this study was to measure the histologic and histomorphometric effects of parathyroid hormone (PTH) treatment on irradiated bone undergoing distraction osteogenesis (DO).MethodsThirty‐four rats were divided into 3 groups. The control group underwent DO and the radiation control group underwent radiotherapy (RT) before DO. The PTH group underwent RT and received PTH during DO. Quantitative histology and histomorphometry were performed.ResultsRT resulted in a depletion of osteocytes and increase in empty lacunae. Treatment with PTH resulted in an increase in osteocyte counts and decrease in empty lacunae (p < .05), restoring osteocytes to levels seen in nonradiated bone (p = .121). RT decreased bone volume to tissue volume (BV‐TV) ratio and increased osteoid volume to tissue volume (OV‐TV) ratio, signifying increased immature bone formation. PTH treatment restored OV‐TV ratio to that observed in nonradiated bone.ConclusionPTH treatment of irradiated bone enhanced bone regeneration and restored osteocyte counts and OV‐TV ratio to levels comparable to nonradiated bone. © 2016 Wiley Periodicals, Inc. Head Neck 39: 464–470, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136287/1/hed24612.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136287/2/hed24612_am.pd

Abscisic Acid: A Novel Nutraceutical for Glycemic Control

Abscisic acid is naturally present in fruits and vegetables, and it plays an important role in managing glucose homeostasis in humans. According to the latest U.S. dietary survey, about 92% of the population might have a deficient intake of ABA due to their deficient intake of fruits and vegetables. This review summarizes the in vitro, preclinical, mechanistic, and human translational findings obtained over the past 15 years in the study of the role of ABA in glycemic control. In 2007, dietary ABA was first reported to ameliorate glucose tolerance and obesity-related inflammation in mice. The most recent findings regarding the topic of ABA and its proposed receptor lanthionine synthetase C-like 2 in glycemic control and their interplay with insulin and glucagon-like peptide-1 suggest a major role for ABA in the physiological response to a glucose load in humans. Moreover, emerging evidence suggests that the ABA response might be dysfunctional in diabetic subjects. Follow on intervention studies in healthy individuals show that low-dose dietary ABA administration exerts a beneficial effect on the glycemia and insulinemia profiles after oral glucose load. These recent findings showing benefits in humans, together with extensive efficacy data in mouse models of diabetes and inflammatory disease, suggest the need for reference ABA values and its possible exploitation of the glycemia-lowering effects of ABA for preventative purposes. Larger clinical studies on healthy, prediabetic, and diabetic subjects are needed to determine whether addressing the widespread dietary ABA deficiency improves glucose control in human

Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study

Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions.Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets.Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) ( < 0.001), stage ( = 0.009), CA125 ( < 0.001), ascites ( < 0.001), and stage-age interaction ( = 0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI).We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool

Lateral flow test engineering and lessons learned from COVID-19

The acceptability and feasibility of large-scale testing with lateral flow tests (LFTs) for clinical and public health purposes has been demonstrated during the COVID-19 pandemic. LFTs can detect analytes in a variety of samples, providing a rapid read-out, which allows self-testing and decentralized diagnosis. In this Review, we examine the changing LFT landscape with a focus on lessons learned from COVID-19. We discuss the implications of LFTs for decentralized testing of infectious diseases, including diseases of epidemic potential, the ‘silent pandemic’ of antimicrobial resistance, and other acute and chronic infections. Bioengineering approaches will play a key part in increasing the sensitivity and specificity of LFTs, improving sample preparation, incorporating nucleic acid amplification and detection, and enabling multiplexing, digital connection and green manufacturing, with the aim of creating the next generation of high-accuracy, easy-to-use, affordable and digitally connected LFTs. We conclude with recommendations, including the building of a global network of LFT research and development hubs to facilitate and strengthen future diagnostic resilience

Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia

Ric Price and colleagues present data from southern Papua, Indonesia, suggesting that malaria resulting from infection withPlasmodium vivax is associated with substantial morbidity and mortality

First Results from a Broadband Search for Dark Photon Dark Matter in the 4444 to 52 μ52\,\mueV range with a coaxial dish antenna

We present first results from a dark photon dark matter search in the mass range from 44 to 52 $\mu{\rm eV}$ ($10.7 - 12.5\,{\rm GHz}$) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area $0.5\,{\rm m}^2$ and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon - photon mixing parameters $\chi \gtrsim 10^{-12}$ in this range at 90% confidence level. This surpasses existing constraints by about two orders of magnitude and is the most stringent bound on dark photons in this range below 49 $\mu$eV.Comment: 7 pages, 4 figure

The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation.

OBJECTIVES: The interaction between the immune system and tumor cells is an important feature for the prognosis and treatment of cancer. Multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) analyses are emerging technologies that can be used to help quantify immune cell subsets, their functional state, and their spatial arrangement within the tumor microenvironment. METHODS: The Society for Immunotherapy of Cancer (SITC) convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to develop best practice guidelines for the optimization and validation of mIHC/mIF assays across platforms. RESULTS: Representative outputs and the advantages and disadvantages of mIHC/mIF approaches, such as multiplexed chromogenic IHC, multiplexed immunohistochemical consecutive staining on single slide, mIF (including multispectral approaches), tissue-based mass spectrometry, and digital spatial profiling are discussed. CONCLUSIONS: mIHC/mIF technologies are becoming standard tools for biomarker studies and are likely to enter routine clinical practice in the near future. Careful assay optimization and validation will help ensure outputs are robust and comparable across laboratories as well as potentially across mIHC/mIF platforms. Quantitative image analysis of mIHC/mIF output and data management considerations will be addressed in a complementary manuscript from this task force

Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer

Mucinous epithelial ovarian cancers are clinically and morphologically distinct from the other histopathologic subtypes of ovarian cancer. Unlike other ovarian subtypes, epidemiologic studies have indicated that tobacco exposure is a significant risk factor for developing mucinous ovarian cancer. Detection of autoantibody reactivity is useful in biomarker discovery and for explaining the role of important pathophysiologic pathways in disease. In order to study if there are specific antibody biomarkers in the plasma samples of mucinous ovarian cancer patients, we have initiated a screen by employing a “reverse capture antibody microarray” platform that uses native host antigens derived from mucinous ovarian tissues as “baits” for the capture of differentially labeled patient and control autoantibodies. 35 autoantibodies that were significantly elevated in the cancer plasma samples compared with healthy controls, and six autoantibodies that segregated smoking and nonsmoking patients were identified. Functional annotation of the antibody targets has identified nine target antigens involved in integrin and Wnt signaling pathways. Immunohistochemistry of archived ovarian specimens showed significant overexpression of eight of the nine target antigens in mucinous ovarian tumor tissues, suggesting that plasma autoantibodies from mucinous ovarian cancer patients might have heightened reactivities with epitopes presented by these overexpressed antigens. Autoantibody profiling may have an unexpected utility in uncovering key signaling pathways that are dysregulated in the system of interest