Optimal Management of Insulin in Patients Undergoing 18F-Fluorodeoxyglucose Positron Emission Tomography Scans.

OBJECTIVE: The management of insulin injections and insulin pumps before 18F-fluorodeoxyglucose-positron emission tomography integrated computerized tomography (FDG-PET/CT) scans is an important area to investigate given the rising rate of diabetes, the significant association between diabetes and cancer, and the complex relationship among glucose, insulin, and FDG tumor uptake. The purpose of this study was to determine the recommendations around subcutaneous insulin administration, insulin pumps, and hybrid closed-loop systems before FDG-PET scans. METHODS: We examined the websites of 100 hospitals selected from the 2022 US News and World Report top cancer hospitals for specific strategies around diabetes medication management before FDG-PET/CT scans. RESULTS: Of the 100 hospital websites, 61 had instructions addressing patients with diabetes. Of the 61 hospitals, 47.5% (n = 29) referred patients to their provider for further instructions, 18% (n = 11) referred patients to their own internal radiology department for further instructions, 16.4% (n = 10) had instructions on oral diabetic medications, 23% (n = 14) had instructions on insulin, and 3.3% (n = 2) had instructions on insulin pump management. Most commonly, instructions were to stop insulin 3 to 4 hours before the study and direct patients to their referring provider for more detailed instructions (n = 7). CONCLUSION: There is a lack of guidance and consensus among US cancer hospitals on managing insulin and continuous subcutaneous insulin infusions before FDG-PET/CT studies and a majority rely on referring providers to advise patients. However, society guidelines offer inconsistent recommendations and little research has been carried out to help guide referring providers. A multidisciplinary panel of specialists could help to guide practitioners on optimal management.

Perplexing Lesion of the Conjunctiva.

An unusual-appearing tumor of the conjunctiva presented in a healthy 11-year-old boy. It was cystic, orange in color, and well encapsulated. After 3 weeks of no response to topical cortisone drops, an excisional biopsy was performed. The histopathology showed the lesion to be a benign lymphoid hyperplasia. [J Pediatr Ophthalmol Strabismus. 2022;59(1):e15-e16.].

Antibodies to human leukocyte antigens and their association with blood product exposures in pediatric patients undergoing cardiac transplantation.

BACKGROUND AND AIMS: Previous blood product exposures may result in the development of antibodies to human leukocyte antigens (HLA). Pediatric heart transplant recipients who have these antibodies experience increased morbidity and mortality after transplantation. In this study, our aims were to confirm the association of previous allogeneic blood product exposures with the formation of anti-HLA antibodies, determine which blood components pose the greatest risk of developing antibodies, and assess differences in outcomes after transplantation between patients who had anti-HLA antibodies and those who did not. METHODS: This retrospective investigation included all children who underwent cardiac transplantation at Children's Healthcare of Atlanta from January 1, 2015 through December 31, 2018. Chart reviews were performed to collect pertinent data. Anti-HLA antibodies were detected by single antigen bead testing. Antibody burden was tabulated using the calculated panel reactive antibody (cPRA) score immediately prior to transplantation. Statistical analyses were conducted to examine differences based on HLA antibody status and identify associations with outcomes of interest. RESULTS: Our results show a significant association between pretransplant blood product exposures and HLA antibody status. Children with a pretransplant blood product exposure had 7.98 times the odds of developing an anti-HLA antibody compared to those without a pretransplant blood product exposure (p = .01). We also found a significant association between a previous red blood cell (RBC) exposure and HLA antibody status (p = .01) which was not found for other blood component exposures. Patients who were HLA antibody positive were more likely to develop a donor-specific antibody (DSA) after transplantation (p = .04). CONCLUSIONS: Exposure to previous allogeneic blood products affects the development of anti-HLA antibodies in children presenting for heart transplantation. Previous RBC exposures resulted in HLA antibody positivity more than other blood component exposures. Importantly, the presence of HLA antibodies was associated with the development of DSAs post-transplantation. Developing transfusion strategies to reduce allogeneic blood product exposures in children who may need future cardiac transplantation should be a high priority.

Monoclonal Gammopathy of Undetermined Significance: Current Concepts and Future Prospects.

PURPOSE OF THE REVIEW: Monoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent precursor condition in the general population, with an approximate 1% annual risk of progression to multiple myeloma (MM) or a related disorder. Our understanding of MGUS and its association with myriad clinical disorders, its progression to MM, and the genomic alterations in the setting of a conducive or permissive microenvironment has deepened considerably. RECENT FINDINGS: Data from gene expression profiling studies have underscored the heterogeneity in the risk of progression of MGUS to MM. Ongoing efforts are being directed toward precise identification of high-risk factors for progression and addressing the role of screening for MGUS in populations at higher risk of MGUS in order to diagnose this precursor condition early, and target modifiable risk factors. Ongoing clinical trials are assessing the role of therapeutic interventions to prevent MGUS from progressing. MGUS is a heterogeneous precursor condition with a risk for progression to symptomatic disease. Future directions are focusing on identifying high-risk populations of MGUS and smoldering multiple myeloma that may benefit with screening and/or early intervention.

Chronic stress induces cell type-selective transcriptomic and electrophysiological changes in the bed nucleus of the stria terminalis.

Distinct regions and cell types in the anterolateral group of the bed nucleus of the stria terminalis (BNSTALG) act to modulate anxiety in opposing ways. A history of chronic stress increases anxiety-like behavior with lasting electrophysiological effects on the BNSTALG. However, the opposing circuits within the BNSTALG suggest that stress may have differential effects on the individual cell types that comprise these circuits to shift the balance to favor anxiogenesis. Yet, the effects of stress are generally examined by treating all neurons within a particular region of the BNST as a homogenoeus population. We used patch-clamp electrophysiology and single-cell quantitative reverse transcriptase PCR (scRT-PCR) to determine how chronic shock stress (CSS) affects electrophysiological and neurochemical properties of Type I, Type II, and Type III neurons in the BNSTALG. We report that CSS resulted in changes in the input resistance, time constant, action potential waveform, and firing rate of Type III but not Type I or II neurons. Additionally, only the Type III neurons exhibited an increase in Crf mRNA and a decrease in striatal-enriched protein tyrosine phosphatase (Ptpn5) mRNA after CSS. In contrast, only non-Type III cells showed a reduction in calcium-permeable AMPA receptor (CP-AMPAR) current and changes in mRNA expression of genes encoding AMPA receptor subunits after CSS. Importantly, none of the effects of CSS observed were seen in all cell types. Our results suggest that Type III neurons play a unique role in the BNSTALG circuit and represent a population of CRF neurons particularly sensitive to chronic stress.

Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning.

Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2-cre and Tac2-GFP mice, we applied a combination of in vivo (optogenetics) and multiple in vitro techniques to further explore the mechanisms of action within the Tac2 pathway. In transgenic mice that express ChR2 solely in Tac2 neurons, in vivo optogenetic stimulation of CeA Tac2-expressing neurons during fear acquisition enhanced fear memory consolidation and drove action potential firing in vitro. In addition, Tac2-CeA neurons were shown to co-express striatal-enriched protein tyrosine phosphatase, which may have an important role in regulating Nk3R signaling during fear conditioning. These data extend our current understanding for the underlying mechanism(s) for the role of the Tac2 pathway in the regulation of fear memory, which may serve as a new therapeutic target in the treatment of fear-related disorders.

Global Similarities and Multifaceted Differences in the Production of Partner-Specific Referential Pacts by Adults with Autism Spectrum Disorders.

Over repeated reference conversational partners tend to converge on preferred terms or referential pacts. Autism spectrum disorders (ASD) are characterized by pragmatic difficulties that are best captured by less structured tasks. To this end we tested adults with ASD who did not have language or intellectual impairments, and neurotypical comparison participants in a referential communication task. Participants were directors, describing unlexicalized, complex novel stimuli over repeated rounds of interaction. Group comparisons with respect to referential efficiency showed that directors with ASD demonstrated typical lexical entrainment: they became faster over repeated rounds and used shortened referential forms. ASD and neurotypical groups did not differ with respect to the number of descriptors they provided or the number of exchanges needed for matchers to identify figures. Despite these similarities the ASD group was slightly slower overall. We examined partner-specific effects by manipulating the common ground shared with the matcher. As expected, neurotypical directors maintained referential precedents when speaking to the same matcher but not with a new matcher. Directors with ASD were qualitatively similar but displayed a less pronounced distinction between matchers. However, significant differences and different patterns of reference emerged over time; neurotypical directors incorporated the new matcher's contributions into descriptions, whereas directors with ASD were less likely to do so.

Metadata extraction using text mining.

Grid technologies have proven to be very successful in the area of eScience, and healthcare in particular, because they allow to easily combine proven solutions for data querying, integration, and analysis into a secure, scalable framework. In order to integrate the services that implement these solutions into a given Grid architecture, some metadata is required, for example information about the low-level access to these services, security information, and some documentation for the user. In this paper, we investigate how relevant metadata can be extracted from a semi-structured textual documentation of the algorithm that is underlying the service, by the use of text mining methods. In particular, we investigate the semi-automatic conversion of functions of the statistical environment R into Grid services as implemented by the GridR tool by the generation of appropriate metadata.