No abstract

In the current report, we describe an 83-year-old biological male who selfidentified as a female by legally changing his first and middle names to female ones and whose death certificate states his sex as a female. The medical history of this individual indicated complete penectomy without further specification. Postmortem physical examination revealed an absence of penis with a large scrotum, transposed urethral orifice, and small testes. The histological analysis of the testes identified abnormal epithelium in the seminiferous tubules that lacked germ and Sertoli cells as well as the interstitium without Leydig cells present. The exome sequencing of the individual's DNA using the Next Generation Sequencing (NGS) Illumina platform revealed no genetic variants associated with either penile or urethral cancer that could have explained the complete penectomy, but pointed toward a potentially impaired production of T3 and T4 thyroid hormones which could account for the observed testicular malformation. Overall, the data obtained raise an important question as to whether the thyroid hormone axis could be an important part of the hormonal architecture supporting male sexual behavior.An 83-year-old TF cadaver was received through Saint Louis University (SLU) School of Medicine Gift of Body Program from an individual who had given his written informed consent. The body was embalmed through the right femoral artery with a mixture of water and a solution (2:1) containing 33.3% glycerin, 28.8% phenol, 4.6% formaldehyde, and 33.3% methanol. Anatomical DissectionThe cadaveric body was dissected according to [11].A. Frolov et al. Histological AnalysisTesticular tissue was procured from the embalmed body. Tissue fixation, paraffin embedding, sectioning, and staining with hematoxylin & eosin were performed by Research Microscopy and Histology Core, Department of Pathology, Saint Louis University (SLU) School of Medicine according to the standardized procedures. Images were captured on Olympus 41BX-EPI microscope equipped with the 10× UPlan FL N, 20× LUCPlan FL, and 40× UPlan FL N objectives. The data acquisition and image analysis were performed by using CellSens Standard software. Bone DensitometryBone density of the lumbar spine and left femoral neck of the embalmed body was measured in triplicates using certified Hologic QDR-4500 X-ray Bone Densitometer in the dual energy X-ray absorptiometry (DEXA) mode following the manufacturer's protocol. The respective average T-score values were used throughout the text. LimitationsThe deleterious (pathologic) genetic variants were identified by the exome sequencing of a single proband. The high scientific value of a single proband approach to unique human cases has been recently demonstrated [27].

Sagittal craniosynostosis (CS) is a pathologic condition that results in premature fusion of the sagittal suture, restricting the transverse growth of the skull leading in some cases to elevated intracranial pressure and neurodevelopmental delay. There is still much to be learned about the etiology of CS. Here, we report a case of 56-year-old male cadaver that we describe as sagittal CS with torus palatinus being an additional anomaly. The craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. The histological analysis of the latter revealed atypical, noncompensatory massive bone overproduction. Exome sequencing of DNA extracted from the cadaveric tissue specimen performed on the Next Generation Sequencing (NGS) platform yielded 81 genetic variants identified as pathologic. Nine of those variants could be directly linked to CS with five of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. The latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case.

BackgroundSitus inversus totalis is a complete reversal of thoracic and abdominal organs. Since only 25% of individuals with situs inversus have primary ciliary dyskinesia (PCD), which is a genetically heterogeneous disorder affecting motile cilia and is thought to be one of the underlining mechanisms of situs inversus, the majority of the latter cases still await their mechanistic elucidation. The present study reports the complete reversal of internal organs in a female cadaver 96 years of age and uses state‐of‐the‐art Next Generation Sequencing (NGS) to detect novel genetic mutations associated with situs inversus totalis.ResultsOur examination of the individual's body revealed that the visceral organs of the abdomen and thorax were mirror‐imaged to normal anatomy. The apex of the heart was directed to the right with a trilobed left lung and bilobed right lung. The liver was situated on the left side of the body, while the spleen and stomach were right sided. Several abdominal vasculature anomalies were also identified. In particular, the common hepatic artery branches from the superior mesenteric artery and the cystic artery branches from the right hepatic artery. There was also a common trunk that gives off the left gastric artery and an accessory right hepatic artery. In order to gain new insights into the molecular mechanisms that govern determination of the left/right asymmetry during the internal organ development, the genetic screen was performed using DNA extracted from the cadaveric tissue and the exome sequencing on the Illumina NGS platform.ConclusionThe present case can be described as situs inversus totalis which is accompanied by abnormal development of abdominal vasculature. The respective genetic analysis could point to a novel and additional to PCD mechanism(s) responsible for the aberrant visceral organ patterning and vascular development in humans.Support or Funding InformationThis study was supported by the Center for Anatomical Science and Education, Department of Surgery, Saint Louis University School of Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Low back pain (LBP) is the leading cause of physical disability worldwide and a substantial socioeconomic burden. Osteoarthritis (OA) of the facet joint is a common source of LBP, however, the relationship between spinal OA and LBP is complex and requires further investigation. We previously reported a spine OA rat model that uses external lumbar spinal linkage to induce hypomobility, leading to significant macroscopic facet joint OA changes. This model may replicate human spinal OA progression and allow mechanistic studies of facet joint OA induced pain. Here we examined the onset and progression of L4/5 and L5/6 facet joint articular cartilage degeneration on the superior articular processes (SAP) following linkage. We hypothesized that spinal linkage would result in an early (1–2 weeks post linkage) thinning of articular cartilage that is progressively greater with longer durations. We used a histological approach based upon previously reported methods to test if spinal linkage is associated with decreases in the ratio of articular cartilage surface length (AS) to total joint surface (JS) length and/or regional articular cartilage surface area in linked and time matched control rats (n=3–4 per group) at 1, 2, 4, and 8 weeks post linkage. Measurements (AS, JS, and area) were performed on brightfield microscopy images (10X objective, Leica DMRB, optronics microfire camera) of sections from the mid‐level of L4/5 and L5/6 facet joints. The tissues were formalin fixed, decalcified, paraffin embedded, sectioned (45 μm thick transverse sections), and stained with Ehrlich's hematoxylin and light green. The JS was divided into 11 equidistant points to define 10 regions from ventral to dorsal and calculate articular cartilage area of each region. Intra‐ and inter‐rater reliability was acceptable for JS (ICC = 0.99, ICC = 0.95), AS (ICC = 0.99, ICC = 0.92), and articular cartilage area (ICC = 0.99, ICC = 0.87). Compared to controls, hypomobility was associated with a significant decrease in the AS/JS ratio (one way ANOVA with Tukey's multiple comparisons, p < 0.05) at 2, 4, and 8 weeks post linkage. Linear regression analysis in 1, 2, 4, and 8 week controls demonstrated no relationship with the AS/JS ratio (r2 = 0.09), while in linked rats longer durations predicted more pronounced decreases in the AS/JS ratio (r2 = 0.84). Descriptive regional analysis supported these findings and revealed that linked rats had reduced cartilage surface area (≥25%) in the ventral‐most (1 medial region) and dorsal‐most (3 lateral regions) regions at week 2 compared with controls. Rats with longer linked durations had greater percentage reductions in cartilage area (≥50%) in the same peripheral regions with additional involvement of adjacent regions and expansion toward the center of the joint stemming mostly from the dorsolateral SAP (dorsal regions with ≥25% reduction: week 4 = 4, week 8 = 5). Our findings suggest that hypomobility results in early (by 2 weeks) and progressive cartilage degeneration in the joint periphery, similar to human facet joint OA. The external spinal linking model creates progressive cartilage loss and may be useful in determining the relationship between OA and pain.