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Transverse myelitis is an inflammatory disorder of the spinal cord that can present with a wide array of lower urinary tract symptoms including urinary retention, frequency, urgency, and urge incontinence.We report a case of a 15 year old male with new onset urinary incontinence who initially presented to the urologist and was subsequently diagnosed with transverse myelitis.

Primary tumors of the epididymis are rare and commonly benign in nature. Leiomyoadenomatoid tumors are a rare subvariant of adenomatoid tumors that combines features of leiomyomas. Tumor histology is notable for tubular spaces lined by mesothelial cells with a proliferative spindle cell component. To the best of our knowledge, few cases have been reported in the literature. We report a case of leiomyoadenomatoid tumor in a 58-year-old male.

Hepatocellular carcinoma (HCC) arises from several different etiologies and carries a poor prognosis. Extrahepatic metastases of HCC are most frequently found in the lungs, lymph nodes, and bones, with adrenal metastases reported in less than 15% of metastatic cases. Herein, we report a case of a 71-year-old man without prior liver disease who presented with a 9-cm right adrenal mass extending into the IVC consistent with HCC on subsequent surgical pathology and immunohistochemical staining. Etiological possibilities for an adrenal tumor as the first presentation of HCC include metastasis from occult primary liver HCC, intra-adrenal hepatic heterotopia, and adrenohepatic fusion.

Subaqueous dredging is a management activity undertaken globally to improve navigation, remove contaminants, mitigate flood risk and/or generate aggregate. Water Injection Dredging (WID) is a hydrodynamic technique involving the turbation and downstream displacement of fine sediments using vessel-mounted water jets. Despite the technique being widely applied internationally, the environmental and ecological effects of WID are poorly understood. For the first time, this study used a Before-After-Control-Impact (BACI) experimental design to assess the effects of WID on water physicochemistry, and macroinvertebrate and fish communities within a 5.7 km-long reach of tidal river. WID targeted the central channel (thalweg) to avoid disturbance of the channel margins and banks. Mean but not peak turbidity levels were substantially elevated, and dissolved oxygen levels were reduced during periods of WID, although effects were relatively short-lived (≈3 h on average). Dredging resulted in significant reductions in benthic macroinvertebrate community abundance (particularly taxa that burrow into fine sediments), taxonomic richness and diversity. In contrast, minor changes were detected in marginal macroinvertebrate communities within and downstream of the dredged reach following WID. Reductions in fish taxonomic richness and diversity were recorded downstream of the dredged reach most likely due to behavioural avoidance of the sediment plume. No visibly stressed or dead fish were sampled during dredging. Results suggest that mobile organisms and marginal communities were largely unaffected by thalweg WID and that the technique represents a more ecologically sensitive alternative to traditional channel margin mechanical dredging techniques.

41-year-old male presented with significant penile swelling following sexual intercourse. Two years earlier while incarcerated, the patient self-inserted a 1.5 cm subcutaneous penile foreign body (FB) made from a domino piece. An original concern for penile fracture was successfully ruled out by penile ultrasound, and computed tomography ruled out deep infection. Bloodwork otherwise revealed leukocytosis, and the patient was admitted for intravenous antibiotics and observation. Penile cellulitis and hematoma clinically improved, and the FB did not require removal. At 18 month follow up, the patient maintains normal urological and sexual function.

Porphyria is a group of metabolic disorders due to altered enzyme activities within the heme biosynthetic pathway. It is a systemic disease with multiple potential contributions to mitochondrial dysfunction and oxidative stress. Recently, it has become possible to measure mitochondrial function from cells isolated from peripheral blood (cellular bioenergetics) using the XF96 analyzer (Seahorse Bioscience). Mitochondrial respiration in these cells is measured with the addition of activators and inhibitors of respiration. The output is measured as the O2 consumption rate (OCR) at basal conditions, ATP linked, proton leak, maximal, reserve capacity, non-mitochondrial, and oxidative burst. We performed cellular bioenergetics on 22 porphyria (12 porphyria cutanea tarda (PCT), seven acute hepatic porphyria (AHP), and three erythropoietic protoporphyria (EPP)) patients and 18 age and gender matched healthy controls. Of porphyria cases, eight were active (2 PCT, 1 EPP, and 5 AHP) and 14 in biochemical remission. The OCR were decreased in patients compared to healthy controls. The bioenergetic profile was significantly lower when measuring proton leak and the non-mitochondrial associated OCR in the eight active porphyria patients when compared to 18 healthy controls. In conclusion, we demonstrate that the bioenergetic profile and mitochondrial activities assessed in porphyria patients and is different than in healthy control individuals. Further, our novel preliminary findings suggest the existence of a mitochondrial dysfunction in porphyria and this may be used as potential non-invasive biomarker for disease activity. This needs to be assessed with a systematic examination in a larger patient cohort. Studies are also suggested to examine mitochondrial metabolism as basis to understand mechanisms of these findings and deriving mitochondrial based therapies for porphyria. Keywords: PCT, AIP, AHP, Protoporphyria, Mitochondrial

We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.

Gene expression profiling is rapidly becoming a mainstay of functional genomic studies. However, there have been relatively few studies of how the data from expression profiles integrate with more classic approaches to examine gene expression. This study used gene expression profiling of a portion of the genome of Saccharomyces cerevisiae to explore the impact of blocks in the isoprenoid biosynthetic pathway on the expression of genes and the regulation of this pathway. Approximately 50% of the genes whose expression was altered by blocks in isoprenoid biosynthesis were genes previously known to participate in the pathway. In contrast to this simple correspondence, the regulatory patterns revealed by different blocks, and in particular by antifungal azoles, was complex in a manner not anticipated by earlier studies.—Dimster-Denk, D., J. Rine, J. Phillips, S. Scherer, P. Cundiff, K. DeBord, D. Gilliland, S. Hickman, A. Jarvis, L. Tong, and M. Ashby. Comprehensive evaluation of isoprenoid biosynthesis regulation in Saccharomyces cerevisiae utilizing the Genome Reproter Matrix™. J. Lipid Res. 1999. 40: 850–860.

Vertical orthogonal joints are a common feature in shallow crustal rocks. There are several competing theories for their formation despite the ubiquity. We examined the exceptional exposures of orthogonal joints in flat-lying Ordovician limestone beds from the Havre-Saint-Pierre Region in Quebec, Canada (north shore of Saint-Lawrence River) to test conceptual models of joint formation in a natural setting. In the region, the spacing of cross-joints is consistently larger than the spacing of systematic joints by a factor of 1.5 approximately. The joint-spacing-to-bed-thickness ratios (s/t) are much larger in these beds (s/t = 4.3 for systematic joints, and 6.4 for cross-joints) than those in higher strained strata along the south shore of the Saint-Lawrence River (s/t = 1), highlighting the effect of tectonic strain in decreasing fracture spacing and block size. The high values of s/t indicate that cross-joint formation was unlikely caused by a switch from compression to tension once a critical s/t ratio for systematic joints was reached (as hypothesized in previous studies). We proposed a new model for the formation of orthogonal joint systems where the principal stress axes locally switch during the formation of systematic fractures. The presence of ladder-shaped orthogonal joints suggests a state of effective stress with σ1∗≫0 > σ2∗>σ3∗ and where σ2∗-σ3∗ is within the range of fracture strength variability at the time of fracture. This research provides a new mechanical model for the formation of orthogonal joint systems and cuboidal blocks.

Cerebral dolichoectasia is an angiopathy involved in a variety of clinical presentations. Patients can rarely present with hydrocephalus as a result of ectatic vessels. We report the case of a 49-year-old male with cerebral dolichoectasia who presented with rare complications of obstructive hydrocephalus, and to our knowledge, a previously unreported cause of fourth ventricular obstruction and cerebellar edema. He represented a diagnostic challenge and after a prolonged admission he was treated successfully with a ventriculoperitoneal shunt. The underlying causes and rarity of diagnosis of cerebral dolichoectasia remain a significant barrier in the optimal treatment of patients as they are often treated for their immediate clinical problem with no definitive treatment for the underlying pathology.