Search

Abstract Background Cervical epidural hematoma (CEH) is a rare but potentially devastating condition, characterized by the accumulation of blood within the epidural space of the cervical spine, leading to spinal cord compression (Perron AD, Huff JS. Spinal cord disorders. In: Marx JA, et al. editors. Rosen’s emergency medicine: concepts and clinical practice. 8th ed. Philadelphia: Saunders; 2013. pp. 1419–27.); (Raasck K, Habis AA, Aoude A, Simoes L, Barros F, Reindl R. Spontaneous spinal epidural hematoma management: a case series and literature review. Spinal Cord Ser Cases. 2017;3:16043. https://doi.org/10.1038/scsandc.2016.43 .); (Ryo Yamamoto M, Ito H, Shimuzu K, Wakabayashi H, Oyama. Two cases of cervical epidural hematoma presenting with left-sided hemiplegia and requiring surgical drainage. Cureus. 2022;14(4):e23915. https://doi.org/10.7759/cureus.23915 .). While trauma and iatrogenic causes are well-documented, cases attributed to neck strain and acupuncture are uncommon. (Raasck K, Habis AA, Aoude A, Simoes L, Barros F, Reindl R. Spontaneous spinal epidural hematoma management: a case series and literature review. Spinal Cord Ser Cases. 2017;3:16043. https://doi.org/10.1038/scsandc.2016.43 .); (Shiraishi S, Goto I, Kuroiwa Y, Nishio S, Kinoshita K. Spinal cord injury as a complication of an acupuncture. Neurology. 1979;29(8):1188–90. https://doi.org/10.1212/wnl.29.8.1188 .) Here, we present two cases of CEH secondary to these unusual aetiologies. Both cases highlight the importance of considering uncommon causes of CEH to ensure early recognition and prompt treatment. Case presentations Case 1 is an 81-year-old lady who presented with left hemiparesis and paraesthesia following a fall with neck strain. Magnetic resonance imaging (MRI) of cervical spine revealed left C3-C7 epidural haematoma with severe cord compression. In Case 2, a 35-year-old gentleman experienced sudden onset numbness and weakness in all limbs just 10 minutes after receiving acupuncture. MRI showed an epidural hematoma at the C2-C4 levels. Both patients underwent immediate surgical decompression and had significant recovery. Conclusion Although CEH is a rare occurrence, it can potentially be a neurosurgical emergency. Physicians must remain cognizant of the diverse aetiologies associated with CEH and the necessity for early recognition and immediate treatment.

Introduction: E-scooters or personal mobility devices (PMDs) have recently been growing in popularity in Singapore. These devices can be especially helpful for those who have reduced mobility or who need to move between several relatively near locations multiples times per day or who simply appreciate the added convenience of having another transportation option. The increasing popularity of PMD has met with growing public concern over safety. Singapore government passed the Active Mobility Act (AMA) in January 2017 to regulate the usage of PMD. In Khoo Teck Puat Hospital, PMD-related accident has increased year on year by 20%–30%. Our study is to compare the incidence and severity of PMD-related accidents before and after the implementation of the AMA. Materials and Methods: A retrospective study of patients presented to the emergency department (ED) of Khoo Teck Puat Hospital for PMD-related accidents between November 2014 and October 2017. In year 1 of the study, we included patients presenting between November 2014 and October 2015. In years 2 and 3, we included patients presenting between November 2015 and October 2016 and November 2016 and October 2017, respectively. Data collected included demographic information, type of device used and impact, outcome, and injury severity score (ISS). Results: A total of 697 PMD-related accidents were seen in our center. We observed an increasing trend of accidents with significant injuries. There were 157 accidents reported in year 1, 233 in year 2, and 307 in year 3. The mean age of patients increased from 28 ± 15 years (range, 5–89 years) in year 1 to 33 ± 15 years (range, 4–83 years). Most patients were males (61.8% in year 1, 76.8% in year 2, and 73.3% in year 3) and Chinese (55.4% in year 1, 62.7% in year 2, and 65.5% in year 3), followed by Malays, Indians, and others. Devices commonly associated with injury were E-scooters, skateboards, and E-bicycles. E-scooters accidents had increased drastically from 12.1% in year 1 to 58.3% in year 3, but E-bicycles and other PMD accidents had decreased in year 3. Most patients were injured from falling off their devices (83.4% in year 1, 83.7% in year 2, and 79.5% in year 3), followed by collisions. Most patients arrived to the ED with own transports and were triaged to the patient acuity category 3 or 4. Most injuries were mild, with ISS

A SPICE macromodel is described which simulates the electrical behaviour of the recently discovered thin-film titanium dioxide (TiO2) memristors. The macromodel allows for fast simulation of circuits that include memristors. The accuracy of the macromodel is demonstrated by comparison with the theoretical behaviour. [ABSTRACT FROM AUTHOR]

An amplitude modulation circuit architecture featuring a recently published titanium dioxide (TiO2) memristor is proposed. The circuit performance is analysed and simulated with the published physical memristor model under the condition of linear dopant drift. The simulated results demonstrate that the performance is well predicted by the mathematical analysis and supports the viability of the design. [ABSTRACT FROM AUTHOR]

Several drugs were found after their market approval to unexpectedly inhibit adrenal 11β-hydroxylase (CYP11B1)-dependent cortisol synthesis. Known side-effects of CYP11B1 inhibition include hypertension and hypokalemia, due to a feedback activation of adrenal steroidogenesis, leading to supraphysiological concentrations of 11-deoxycortisol and 11-deoxycorticosterone that can activate the mineralocorticoid receptor. This results in potassium excretion and sodium and water retention, ultimately causing hypertension. With the risk known but usually not addressed in preclinical evaluation, this study aimed to identify drugs and drug candidates inhibiting CYP11B1. Two conceptually different virtual screening methods were combined, a pharmacophore based and an induced fit docking approach. Cell-free and cell-based CYP11B1 activity measurements revealed several inhibitors with IC 50 values in the nanomolar range. Inhibitors include retinoic acid metabolism blocking agents (RAMBAs), azole antifungals, α 2 -adrenoceptor ligands, and a farnesyltransferase inhibitor. The active compounds share a nitrogen atom embedded in an aromatic ring system. Structure activity analysis identified the free electron pair of the nitrogen atom as a prerequisite for the drug-enzyme interaction, with its pK a value as an indicator of inhibitory potency. Another important parameter is drug lipophilicity, exemplified by etomidate. Changing its ethyl ester moiety to a more hydrophilic carboxylic acid group dramatically decreased the inhibitory potential, most likely due to less efficient cellular uptake. The presented work successfully combined different in silico and in vitro methods to identify several previously unknown CYP11B1 inhibitors. This workflow facilitates the identification of compounds that inhibit CYP11B1 and therefore pose a risk for inducing hypertension and hypokalemia., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alex Odermatt reports financial support was provided by Swiss Centre for Applied Human Toxicology., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17β-estradiol (estradiol) biosynthesis. This study evaluated a novel approach to detect disturbances of steroidogenesis in H295R cells, exemplified by prochloraz and five anabolic steroids. Steroid profiles were assessed by an untargeted LC-MS-based method, providing a relative quantification of 57 steroids annotated according to their accurate masses and retention times. Such a panel of steroids included several mineralocorticoids, glucocorticoids, progestins and adrenal androgens. The coverage of a high number of metabolites in this extended steroid profiling facilitated grouping of chemicals with similar effects and detecting subtler differences between chemicals. It allowed, for example, distinguishing between the effects of turinabol and oxymetholone, supposed to act similarly in a previous characterization including only nine adrenal steroids. Furthermore, the results revealed that product/substrate ratios can provide superior information on altered enzyme activities compared to individual metabolite levels. For example, the 17α-hydroxypregnenolone/pregnenolone ratio was found to be a more sensitive marker for detecting 17α-hydroxylase inhibition by prochloraz than the corresponding individual steroids. These results illustrate that chemical grouping and calculation of product/substrate ratios can provide valuable information on mode-of-action and help prioritizing further experimental work., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Recently, different reproductive modes were proposed between the emerging forest pathogen Hymenoscyphus fraxineus and its closely related avirulent sister species, Hymenoscyphus albidus. In the present study, inter- and intraspecific crosses were performed to experimentally assess the reproduction barriers between the two species and to verify H. albidus' putative haploid-selfing reproductive mode. By means of H. fraxineus-specific microsatellite markers, no hybridization was observed in 29 apothecia that emerged from inter-specific crosses, suggesting reproduction barriers are well-established. In a similar experimental setup, we used two newly developed polymorphic H. albidus-specific microsatellites to show that haploid-selfing is H. albidus' only reproductive mode (N=17 apothecia). Further to this, the reproductive modes of both species were investigated under natural conditions. Microsatellite allele-segregation studies of H. fraxineus' single-spore progeny of apothecia (N=31) from field samples suggest that often more than two paternal nuclei are involved in mating. In contrast, analysis of single-spore progeny of field-collected H. albidus apothecia (N=21) confirmed the solely haploid-selfing reproductive mode detected in vitro. Furthermore, we present the complete mating type 1-1 locus of H. fraxineus and report the finding of three additional genes within this region; the as yet unobserved typical mating type gene MAT1-1-1, a DNA polymerase zeta catalytic subunit-like gene and a pre-mRNA-splicing factor SLU7-like gene. The same genes were also detected in the homothallic mating type locus of H. albidus. Further analysis confirmed the expression of all typical mating type genes (MAT1-2-1, MAT1-1-3, MAT1-1-1) in both species. Interestingly, the MAT1-1-3 gene of homothallic H. albidus is expressed despite three stop codons interrupting the coding sequence. Overall, our findings highlight vital differences in the reproduction systems of the two species and suggest that interspecific hybridization is not possible., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The cellobiohydrolase I gene, cbh1, has been cloned from an enhanced cellulase-producing strain, Trichoderma koningii G-39. Sequence comparisons show that T. koningii cbh1 is identical to that of T. reesei with the exception of 6 bp--two causing silent substitutions in the coding region, three differing in one of the introns, and one in 5'-noncoding region. Thus, it should encode an identical CBHI to that of T. reesei despite the differences in morphological characters of the two species. Analysis of approximately 1.4 kb of the 5' flanking region shows a number of surprisingly interesting putative regulatory features. There are no unusual features within about 600 bp upstream of the translation start ATG. However, prior to the 600-bp region, there are seven CAAT sequences, a number of direct and inverted repeats, and two C/T-rich regions. Also, there are five consensus 5'-(G/C)PyGGGG-3' sequences that have been identified to be carbon catabolite repressor binding sites of Aspergillus nidulans CREA and Saccharomyces cerevisiae MIG1 repressors. The structural organization around these consensus sequence regions is similar to those of A. nidulas alcR and alcA promoters. While the production of large amounts of CBHI by T. koningii upon induction apparently correlates with the large number of CAAT boxes in the 5' upstream untranslated region of cbh1, the presence of five CREA/MIG1 repressor-binding consensus sequences in the region suggests the wide-domain carbon catabolite repression regulatory system that controls the A. nidulans ethanol regulon, and yeast GAL genes transcription might also be operative and responsible for regulation of T. koningii cbh1 transcription.