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Background: The survival of traumatic cardiopulmonary arrest (TCA) requiring pre-hospital cardiopulmonary resuscitation (P-CPR) is abysmal across age groups. We aim to describe the mechanisms of injury and outcomes of children suffering from TCA leading to P-CPR at our institution., Methods: A retrospective review was conducted to identify children ages 0-17 years who suffered TCA leading to P-CPR at our institution between 5/2009 and 3/2020. For analysis, patients were stratified into those still undergoing CPR at arrival and those who attained pre-hospital return of spontaneous circulation (ROSC). Primary outcome was discharge alive from the hospital., Results: P-CPR was initiated for 48 patients who had TCA; 23 had pre-hospital ROSC. Of the 25 children undergoing CPR at presentation, none survived to discharge. The median duration of CPR, from initiation to time of death declaration was 34 min [29,50]. Seventeen patients died after resuscitation attempts in the ED, while 8 died after admission to the PICU. Of the 23 patients who attained pre-hospital ROSC, 6 survived to discharge. All survivors required intensive rehabilitation services at discharge and at most recent follow-up, 5 had residual deficits requiring medical attention., Conclusion: There are poor outcomes in children with pre-hospital traumatic cardiopulmonary arrest, particularly in those without pre-hospital ROSC. These data further support the need for standardized guidelines for resuscitation in children with traumatic cardiopulmonary arrest., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: There are disparate findings in the literature on the impact of race and insurance status on gonadal loss in testicular torsion. We sought to determine if race or levels of social vulnerability influence the rate of torsion or gonadal loss., Methods: Retrospective cross-sectional review between December 2017 and September 2019. Social vulnerability index was dichotomized using the 75th percentile. Primary outcome was the diagnosis of testicular torsion., Results: 515 patients were included. There was no difference in median age, torsion diagnosis, and orchiectomy rate between the two institutions. Black/African American patients were >3 times more likely than Caucasian patients to be diagnosed with TT when controlled for dichotomized SVI, insurance, and age (OR 3.39, 95% CI 1.74 - 6.61, p < 0.01)., Conclusion: Black/African American children have an increased risk of testicular torsion. Despite these patients having higher levels of social vulnerability, it was not associated., (Copyright © 2022 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Eighteen natural products sourced from Australian micro- or macro-fungi were screened for antibacterial and antifungal activity. This focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. Chemical investigations of the re-fermented culture from the endophytic fungus Pestalotiopsis sp. yielded three caprolactam analogues, pestalactams D-F, along with larger quantities of the known metabolite pestalactam A, which was methylated using diazomethane to yield 4-O-methylpestalactam A. The chemical structures of the previously undescribed fungal metabolites were determined by analysis of 1D/2D NMR and MS data. The structure of 4-O-methylpestalactam A was confirmed following single crystal X-ray diffraction analysis. The antibacterial and antifungal activity of all compounds was assessed, which identified three compounds, (1S,3R)-austrocortirubin, (1S,3S)-austrocortirubin, and 1-deoxyaustrocortirubin with mild activity (100 μM) against Gram-positive isolates and one compound, 2-hydroxy-6-methyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, with activity against Cryptococcus neoformans and Cryptococcus gattii at 50 μM., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAHs) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LCs) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LCs rapidly internalize and accumulate DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1 independent. Thus, LCs make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation.

Mouse double minute 2 (MDM2) has a phosphorylation site within a lid motif at Ser17 whose phosphomimetic mutation to Asp17 stimulates MDM2-mediated polyubiquitination of p53. MDM2 lid deletion, but not Asp17 mutation, induced a blue shift in the λ(max) of intrinsic fluorescence derived from residues in the central domain including Trp235, Trp303, Trp323, and Trp329. This indicates that the Asp17 mutation does not alter the conformation of MDM2 surrounding the tryptophan residues. In addition, Phe235 mutation enhanced MDM2 binding to p53 but did not stimulate its ubiquitination function, thus uncoupling increases in p53 binding from its E3 ubiquitin ligase function. However, the Asp17 mutation in MDM2 stimulated its discharge of the UBCH5a-ubiquitin thioester adduct (UBCH5a is a ubiquitin-conjugating enzyme E2D 1 UBC4/5 homolog yeast). This stimulation of ubiquitin discharge from E2 was independent of the p53 substrate. There are now four known effects of the Asp17 mutation on MDM2: (i) it alters the conformation of the isolated N-terminus as defined by NMR; (ii) it induces increased thermostability of the isolated N-terminal domain; (iii) it stimulates the allosteric interaction of MDM2 with the DNA-binding domain of p53; and (iv) it stimulates a novel protein-protein interaction with the E2-ubiquitin complex in the absence of substrate p53 that, in turn, increases hydrolysis of the E2-ubiquitin thioester bond. These data also suggest a new strategy to disrupt MDM2 function by targeting the E2-ubiquitin discharge reaction., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

There are more than 200,000 Canadians living with permanent pacemakers or implantable defibrillators, many of whom will require surgery or invasive procedures each year. They face potential hazards when undergoing surgery; however, with appropriate planning and education of operating room personnel, adverse device-related outcomes should be rare. This joint position statement from the Canadian Cardiovascular Society (CCS) and the Canadian Anesthesiologists' Society (CAS) has been developed as an accessible reference for physicians and surgeons, providing an overview of the key issues for the preoperative, intraoperative, and postoperative care of these patients. The document summarizes the limited published literature in this field, but for most issues, relies heavily on the experience of the cardiologists and anesthesiologists who contributed to this work. This position statement outlines how to obtain information about an individual's type of pacemaker or implantable defibrillator and its programming. It also stresses the importance of determining if a patient is highly pacemaker-dependent and proposes a simple approach for nonelective evaluation of dependency. Although the document provides a comprehensive list of the intraoperative issues facing these patients, there is a focus on electromagnetic interference resulting from electrocautery and practical guidance is given regarding the characteristics of surgery, electrocautery, pacemakers, and defibrillators which are most likely to lead to interference. The document stresses the importance of preoperative consultation and planning to minimize complications. It reviews the relative merits of intraoperative magnet use vs reprogramming of devices and gives examples of situations where one or the other approach is preferable., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Disorders of the optic tract, lateral geniculate nucleus, optic radiation, and occipital lobe - collectively called the retrochiasmal visual pathways - are commonly encountered in neurological practice, and may result from a number of causes. The major visual morbidity of retrochiasmal disease is the homonymous visual field defect, which is found in approximately 8% of stroke patients. A homonymous visual field defect may have profound legal, occupational, and financial consequences for patients, with many patients unable to read, drive, or return to work after sustaining retrochiasmal damage. Some homonymous hemianopias may improve, usually within days of a cerebral infarction, but remain stable after 3 months. Although treatment options are limited to those of the underlying cause, appropriate counseling and low-vision rehabilitation may be helpful., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To identify risk factors for idiopathic intracranial hypertension (IIH) in men., Design: Case-control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis., Setting: Outpatient clinics in two US tertiary care centers., Participants: The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category., Main Outcome Measures: Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel-Haenszel odds ratios and mixed-effects logistic regression models accounted for matching., Results: Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6-54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5-12.9; p=0.03)., Conclusions: Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men.

The independent evolution of sex chromosomes in many eukaryotic species raises questions about the evolutionary forces that drive their formation. Recent advances in our understanding of these genomic structures in mammals in parallel with alternate models such as the monotremes, fish, dioecious plants, and fungi support the idea of a remarkable convergence in structure to form large, non-recombining regions with discrete evolutionary strata. The discovery that evolutionary events similar to those that have transpired in humans have also occurred during the formation of sex chromosomes in organisms as divergent as the plant Silene, the fungus Cryptococcus and the fish medaka highlights the importance of future studies in these systems. Such investigation will broaden our knowledge of the evolution and plasticity of these ubiquitous genomic features underlying sexual dimorphism and reproduction.

A 37-year-old man who had successfully undergone cardiac transplantation for dilated cardiomyopathy presented with a history of severe pain over his left shoulder, rib cage and thoracic spine. Clinical examination revealed the presence of bony tenderness over these sites, but there was no other clinical evidence of malignancy. Further investigations suggested the presence of multiple bony metastases. Bone biopsy revealed extensive bone marrow infiltration by large undifferentiated cells showing pronounced cytoplasmic vacuolation with a striking granulomatous reaction. Immunocytochemistry revealed these anaplastic cells to be cytokeratin and placenta-like alkaline phosphatase positive but S100, CD30 and lymphoid marker negative. Analyses by in situ hybridisation of these cells revealed no evidence of Epstein-Barr virus infection. Overall the pathology suggested a diagnosis of metastatic seminoma. Confirmation of this diagnosis was obtained by the analysis of serum human chorionic gonadotrophin which was elevated at 90 IU/l. In the absence of testicular or retroperitoneal disease, it is very likely that this unusual case of metastatic seminoma was related to the patient's immunosuppressive therapy, which at diagnosis included cyclosporin and prednisolone. The patient was successfully treated with cisplatin based chemotherapy and decreased immunosuppression and remains in complete remission one year after completion of chemotherapy. Seminoma is an uncommon complication of prolonged immunosuppression with very few cases being described in the literature post-organ transplantation. This case shows that the clinical presentation of this treatable tumour in this patient population can be unusual and difficult to diagnose.

The use of Fraser Broth enables the presumptive detection of Listeria spp. within 48 h, thereby producing major cost and time savings when compared to existing methods. Fraser Broth was developed by modification of the USDA secondary enrichment broth through the addition of lithium chloride and ferric ammonium citrate. Esculin hydrolysis in Fraser Broth results in the production of a black precipitate. Since all Listeria spp. hydrolyse esculin, cultures which do not blacken can be considered to be Listeria -free. The efficacy of Fraser Broth was documented by testing a wide range of food and environmental samples from food processing facilities in parallel with the methods used by the government regulatory agencies. Fraser Broth inoculated from the USDA primary enrichment was found to be more sensitive than either Fraser Broth inoculated from the FDA enrichment or the existing FDA method in the analysis of ice cream products.