Exosomes are extracellular vesicles which are released from healthy and tumor cells into blood circulation. Unique biomolecular cargos such as RnA and protein are loaded in these vesicles. these molecules may have biological functions such as signaling, cell communications and have the potential to be analyzed as biomarkers. In this initial study, we describe the analysis of exosomes in the serum of healthy subjects, intraductal papillary mucosal neoplasms and pancreatic ductal adenocarcinoma including the characterization of their RNA cargos by next generation sequencing (EXO-NGS). Results indicate the presence of a wide variety of RNAs including mRNA, miRNA, lincRNA, tRNA and piRNA in these vesicles. Based on the differential mRNA expression observed upon EXO-NGS analysis, we independently evaluated two protein coding genes, matrix metalloproteinase-8 (MMP-8) and transcription factor T-Box 3 (TBX3) by qRT-PCR for selective expression in the serum samples. Results indicate a variable expression pattern of these genes across serum samples between different study groups. Further, qRT-PCR analysis with the same serum exosomes processed for EXO-NGS, we observed two long non-coding RNAs, malat-1 and CRNDE to be variably expressed. Overall, our observations emphasize the potential value of different exosome components in distinguishing between healthy, premalignant and malignant conditions related to the pancreas.

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Diabetic embryopathy is defined as congenital anomalies that are linked to maternal diabetes. The association between diabetes and fetal, neonatal, and long-term complications is well-established. These complications include organ or structural maldevelopment, fetal growth abnormalities, and learning/psychiatric comorbidities. Recent studies have elucidated the pathophysiology behind these conditions and outlined new management approaches. Caudal regression syndrome, also known as sacral agenesis, is a well-known but less described complication of maternal diabetes. The purpose of this review is to summarize existing research on common neonatal morbidities in infants of mothers with diabetes with a focus on caudal regression syndrome and its long-term associations.

Objective: Ultrasound is a common imaging modality used to evaluate spinal anomalies in newborns. However, many indications for the use of spinal ultrasound are associated with low diagnostic yield. The purpose of this study is to evaluate the indications and the diagnostic utility of spinal ultrasounds performed in newborns. We also review patient presentations for caudal regression syndrome that was identified from the ultrasounds performed. Study Design: This study is a retrospective review of spinal ultrasounds performed between January 1, 2006 to December 31, 2021 in newborns at a single institution. Indications for each ultrasound and any associated abnormalities were noted. Infants with abnormal ultrasounds showing caudal regression syndrome are described with their long – term medical outcomes. Results: A total of 592 ultrasounds were performed during the specified time period of which 72 (12%) were abnormal. Presence of a sacral dimple was the most common indication for performing a spinal ultrasound, although only 14 (4%) were identified as abnormal. Of these 14, six (43%) were further evaluated by spinal MRI at the recommendations of a pediatric radiologist and of these only two (14%) had abnormal MRI findings. The two newborns with abnormal MRI findings had mothers with diabetes mellitus in their pregnancies. Of note, one additional newborn had abnormalities on spinal US that was never confirmed on MRI due to being lost to followup. Among the other indications, anorectal anomalies (odds ratio [OR] 7.55; 95% confidence interval [CI] 3.01 to 18.91), spinal mass (OR, 17.99; 95% CI 7.86 to 41.2), and meningocele were most associated with abnormal findings. Conclusion: Overall, spinal US has a low diagnostic yield. Sacral dimple was the most common indication for performing a spinal US but had a low yield with few long-term sequelae. Anorectal anomalies had a strong association with abnormal US findings.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Offspring of diabetic mothers have a higher incidence of birth defects. One such defect is sacral agenesis. It is a rare developmental abnormality consisting of the absence of part or all of the sacrum. Offspring of mothers with PGDM have a higher risk of sacral agenesis compared to offspring of mothers with no diabetes. Despite this, there are currently no guidelines to routinely screen offspring of diabetic mothers for sacral agenesis. Research has shown that early intervention for sacral agenesis decreases the risk for future urinary and musculoskeletal complications and thus improves overall prognosis. Objective Determine the utility of prospective spinal ultrasound in infants of mothers with PGDM for the diagnosis of sacral agenesis. Methods This prospective observational pilot study was completed at Women’s and Children’s Hospital in Columbia, Missouri between May 1, 2020 and December 30, 2022. Infants born to mothers with PGDM and with normal spinal examinations were included. A total of 22 mother-infant dyads were enrolled in the study and prospectively screened with spinal ultrasound. The study was registered on ClinicalTrials.gov (Identifier-NCT05033275). Results Twenty-two spinal ultrasounds were performed over the course of this study with three (14%) resulting in abnormal findings that required further imaging. Follow-up with magnetic resonance imaging found one case of tethered cord syndrome. Conclusion Prospective screening in infants of mothers with PGDM found no cases of sacral agenesis but did identify tethered cord syndrome. This finding suggests that risk stratified screening of mothers with diabetes might be a reasonable approach to care.

The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl)-homoserine lactone (C12-HSL) on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA) cells (DU145 and LNCaP) and prostate small cell neuroendocrine carcinoma (SCNC) PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1) were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.