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Context: Active acromegaly is characterized by lipolysis-induced insulin resistance, which suggests adipose tissue (AT) as a primary driver of metabolic aberrations., Objective: To study the gene expression landscape in AT in patients with acromegaly before and after disease control in order to understand the changes and to identify disease-specific biomarkers., Methods: RNA sequencing was performed on paired subcutaneous adipose tissue (SAT) biopsies from six patients with acromegaly at time of diagnosis and after curative surgery. Clustering and pathway analyses were performed in order to identify disease activity-dependent genes. In a larger patient cohort (n = 23), the corresponding proteins were measured in serum by immunoassay. Correlations between growth hormone (GH), insulin-like growth factor I (IGF-I), visceral AT (VAT), SAT, total AT, and serum proteins were analyzed., Results: 743 genes were significantly differentially expressed (P-adjusted < .05) in SAT before and after disease control. The patients clustered according to disease activity. Pathways related to inflammation, cell adhesion and extracellular matrix, GH and insulin signaling, and fatty acid oxidation were differentially expressed.Serum levels of HTRA1, METRNL, S100A8/A9, and PDGFD significantly increased after disease control (P < .05). VAT correlated with HTRA1 (R = 0.73) and S100A8/A9 (R = 0.55) (P < .05 for both)., Conclusion: AT in active acromegaly is associated with a gene expression profile of fibrosis and inflammation, which may corroborate the hyper-metabolic state and provide a means for identifying novel biomarkers., Competing Interests: Conflicts of interest: C.M.F. and M.C.A.S. received lecture fees from Pfizer. J.D. received unrestricted research grants and lecture fees from Pfizer and IPSEN. A.H. received lecture fees from Recordati and Ipsen. J.B. received lecture fees from Ipsen and Pfizer and served as an advisory board member for Pfizer. N.C.O. received lecture fees from CORE2ED (supported by a medical education grant from Ipsen) and Pfizer. A.Y.M.S., A.E.M., T.U., L.G.O., and J.O.L.J. have nothing to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The presence of antibodies directed against human leukocyte antigens (HLA) expressed on donor cells is a significant risk factor for serious clinical complications after transplantation. The crossmatch assay is one of the most important tests available for the detection of donor-specific antibodies in potential allograft recipients. Early crossmatch methods utilized complement-dependent cytotoxicity, which is useful for detecting the donor-specific anti-HLA antibodies responsible for hyperacute allograft rejection but lacks adequate sensitivity. Consequently, more sensitive crossmatch methods have been developed, ultimately leading to the flow cytometry crossmatch as the currently preferred methodology. Herein, we review the evolution of the crossmatch assay and the most important factors to consider when performing and interpreting the results of this fundamental assay for ensuring the long-term survival of the transplanted organ.

In primary prostate cancer, the common multifocality and heterogeneity are major obstacles in finding robust prognostic tissue biomarkers. The long noncoding RNA SCHLAP1 has been suggested, but its prognostic value has not been investigated in the context of tumor heterogeneity. In the present study, expression of SCHLAP1 was investigated using real-time RT-PCR in a multisampled series of 778 tissue samples from radical prostatectomies of 164 prostate cancer patients (median follow-up time 7.4 y). The prognostic value of SCHLAP1 was evaluated with biochemical recurrence as endpoint. In total, 29% of patients were classified as having high expression of SCHLAP1 in at least one malignant sample. Among these, inter- and intrafocal heterogeneity was detected in 72% and 56%, respectively. High expression of SCHLAP1 was shown to be a predictor of biochemical recurrence in both uni- and multivariable cox regression analyses (P < 0.001 and P = 0.02). High expression of SCHLAP1 was also significantly associated with adverse clinicopathological characteristics, including grade group, high pT stage, invasive cribriform growth/intraductal carcinoma of the prostate, and reactive stroma. In conclusion, high expression of SCHLAP1 in at least one malignant sample is a robust prognostic biomarker in primary prostate cancer. For the first time, high SCHLAP1 expression has been associated with the aggressive histopathologic feature reactive stroma. The expression of SCHLAP1 is highly heterogeneous, and analysis of multiple samples is therefore crucial in determination of the SCHLAP1 status of a patient., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differences in cerebral activity during hypoglycaemia and cognitive testing in two groups of healthy men with different basal RAS activity., Methods: Ten healthy men with high RAS activity and 10 with low activity underwent six oxygen-15-labelled water positron emission tomography scans: twice during normoglycaemia, twice during insulin-induced hypoglycaemia and twice during post-hypoglycaemia. During the scans, the subjects performed a computer-based reaction time test., Results: Occipital areas were consistently more activated in the low RAS group than in the high RAS group throughout all three conditions. During normoglycaemia, the frontal region was more activated in the low RAS group than in the high RAS group. During hypoglycaemia, the high RAS group was more activated in the pituitary gland than the low RAS group., Conclusion: Basal RAS activity influenced cerebral activity. Low RAS was associated with more pronounced cortical activation in all glycaemic conditions. High RAS was associated with pituitary activation during hypoglycaemia and post-hypoglycaemia, and this was associated with a greater growth hormone response.

The risk of severe hypoglycemia in patients with type I diabetes and high basal activity in the renin-angiotensin system (RAS) is significantly higher than in patients with low basal RAS activity. In healthy men, we tested the hypothesis that differences in spontaneous RAS activity are associated with differences in cerebral activity responses during mild hypoglycemia. A total of 10 healthy men with high and 10 with low spontaneous RAS activity were selected. An H(2)(15)O-PET (H(2)(15)O-positron emission tomography) study was conducted with a series of six scans, i.e., two during normoglycemia, two during hypoglycemia, and two after hypoglycemia. The mean plasma glucose concentration was similar in both the groups (i.e., 2.1 mmol/L (s.d.: 0.4) in the low RAS group and 2.2 mmol/L (s.d.: 0.4) in the high RAS group (P=0.47)). The high RAS group has lower cerebral activity in the frontal area and a higher cerebral activity in the entorhinal area that expanded to include the parahippocampal gyrus after hypoglycemia. Our findings suggest that the high RAS group to a lesser extent than the low RAS group activates areas involving executive function that may explain the correlation between high basal RAS activity and risk of severe hypoglycemia in type I diabetes.

A convenience survey of 702 certified pesticide applicators was conducted in three states to assess the use of 16 types of engineering controls and 13 types of personal protective equipment (PPE). Results showed that 8 out of 16 engineering devices were adopted by more than 50% of the respondents. The type of crop, size of agricultural operation, and the type of pesticide application equipment were found to influence the adoption of engineering controls. Applicators working on large farms, users of boom and hydraulic sprayers, and growers of field crops were more likely to use engineering devices. Respondents reported a high level of PPE use, with chemical-resistant gloves showing the highest level of compliance. An increase in pesticide applicators wearing appropriate headgear was reported. The majority of respondents did not wear less PPE simply because they used engineering controls. Those who did modify their PPE choices when employing engineering controls used tractors with enclosed cabs and/or were vegetable growers.

In the United States, environmental regulatory agencies are required to use "best available" scientific information when making decisions on a variety of issues. However, agencies are often hindered by coarse or incomplete data, particularly as it pertains to threatened and endangered species protection. Stakeholders often agree that more resolute and integrated processes for decision-making are desirable. We demonstrate a process that uses species occurrence data for a federally endangered insect (Karner blue butterfly), a readily available habitat modeling tool, and spatially explicit information about an important Michigan commodity (tart cherries). This case study has characteristics of many protected species regulatory decisions in that species occurrence data were sparse and unequally distributed; regulatory decisions (on pesticide use) were required with potentially significant impacts on a viable agricultural industry; and stakeholder relations were diverse, misinformed, and, in some situations, unjustly contentious. Results from our process include a large-scale, empirically derived habitat suitability map for the focal species and a risk ranking of tart cherry orchards with risk based on the likelihood that pesticide applications will influence the focal protected species. Although the majority (77%) of pesticide-influence zones overlapped Karner blue butterfly habitat, risk scores associated with each orchard were low. Through our process we demonstrated that spatially explicit models can help stakeholders visualize and quantify potential protected species effects. In addition, model outputs can serve to guide field activities (e.g., species surveys and implementation of pesticide buffer zones) that help minimize future effects.

Blurred vision and cognitive difficulties are prominent symptoms during acute insulin-induced hypoglycemia. Our hypothesis was that changes in cerebral activity reflect these symptoms. Positron emission tomography (PET) with oxygen-15-labelled water was used to measure relative changes in regional cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal counterregulatory response. During the low cognitive load, rCBF decreased in response to hypoglycemia in a large bilateral area in the posterior part of the temporal lobe, and rCBF increased bilaterally in the anterior cingulate gyrus, the right frontal gyrus, the fusiform gyrus, thalamus, and the left inferior part of the frontal gyrus. During the high cognitive load, rCBF decreased bilaterally in a large region in the posterior part of the temporal gyrus and increased in the left and right anterior cingulate gyrus, left and right frontal gyrus, right parahippocampal and lingual gyrus, and left superior temporal gyrus. Visual impairment during hypoglycemia was associated with deactivation in the ventral visual stream. The anterior cingulate gyrus was activated during hypoglycemia in a load-dependent manner. Areas on the frontal convexity were differentially activated in response to the cognitive load during hypoglycemia. Our findings suggest that hypoglycemia induces changes in sensory processing in a cognition-independent manner, whereas activation of areas of higher order functions is influenced by cognitive load as well as hypoglycemia., ((c) 2009 Wiley-Liss, Inc.)