Kjeldgaardotte7966

Non-ribosomal peptides are a group of structurally diverse natural products with various important therapeutic and agrochemical applications. Bacterial pyrrolizidine alkaloids (PAs), containing a scaffold of two fused five-membered ring system with a nitrogen atom at the bridgehead, have been found to originate from a multidomain non-ribosomal peptide synthetase to generate indolizidine intermediates, followed by multistep oxidation, catalysed by single Bayer-Villiger (BV) enzymes, to yield PA scaffolds. Although bacterial PAs are rare in natural product inventory, bioinformatics analysis suggested that the biosynthetic gene clusters (BGCs) that are likely to be responsible for the production of PA-like metabolites are widely distributed in bacterial genomes. However, most of the strains containing PA-like BGCs are not deposited in the public domain, therefore preventing further assessment of the chemical spaces of this group of bioactive metabolites. Here, we report a genomic scanning strategy to assess the potential of PA metabolites production in our culture collection without prior knowledge of genome information. Among the strains tested, we found fifteen contain the key BV enzymes that are likely to be involved in the last step of PA ring formation. Subsequently one-strain-many-compound (OSMAC) method, supported by a combination of HR-MS, NMR, SMART 2.0 technology, and GNPS analysis, allowed identification and characterization of a new [5 + 7] heterobicyclic carbamate, legoncarbamate, together with five known PAs, bohemamine derivatives, from Streptomyces sp. CT37, a Ghanaian soil isolate. The absolute stereochemistry of legoncarbamate was determined by comparison of measured and calculated ECD spectra. Legoncarbamate displays antibacterial activity against E. coli ATCC 25922 with an MIC value of 3.1 μg/mL. Finally, a biosynthetic model of legoncarbamate and other bohemamines was proposed based on the knowledge we have gained so far.Amyotrophic lateral sclerosis (ALS) is characterized by progressive onset motor deficits with heterogenous presentations ranging from dysarthria to foot drop. Approximately 20% of the patients present with focal bulbar symptoms, in which some may remain restricted to bulbar region (isolated bulbar palsy), and the remaining eventually spreads to involve other body regions (classical ALS). Without accompanying upper and lower motor neurons signs elsewhere, differential diagnoses for isolated bulbar symptoms are extensive, include ALS variants as well as potentially treatable mimics. Therefore, it is important to take heed on every possible aetiology that may disrupt the hypoglossal nucleus, nerve, or lingual muscle itself. Herein, we illustrated a rare presentation of Group A basilar invagination, which mimicked bulbar-onset ALS.

Neuromyelitis optica spectrum disorder (NMOSD) is an auto-immune disease of the central nervous system (CNS) associated with the IgG-antibody against aquaporin-4 (AQP4-IgG). There is little published epidemiology of NMOSD from sub-Saharan Africa (SSA).

We retrospectively collated NMOSD cases admitted to our tertiary regional neurology centre.

We identified 11 cases (10 female, average age 30years). 64% (7/11) were seropositive for AQP4-IgG, measured using indirect immunofluorescence. The remaining cases could either not afford tests, or had pathognomonic radiological features. 57% (4/7) of seropositive cases had concurrent/recent CNS infection. All patients were treated with high-dose intravenous methylprednisolone (IVMP), and 36% (4/11) also had plasma exchange. Only 55% (6/11) of the patients were seen by a neurologist at presentation they had less relapses (1.3 vs 2.4), less diagnostic delay (2.3 vs 7.4months), and were less disabled at the end of our review period. 10 cases were immunosuppressed long-term 60% on mycophenolate, 30% azathioprine, and one on rituximab.

Our study is the largest case series of NMOSD from the East Africa region. Patients faced challenges of access to appropriate and affordable testing, and timely availability of a neurologist at onset, which had impacts on their functional outcomes. The majority of the seropositive cases had recent/concurrent CNS infections, suggesting triggered auto-immunity.

Our study is the largest case series of NMOSD from the East Africa region. Patients faced challenges of access to appropriate and affordable testing, and timely availability of a neurologist at onset, which had impacts on their functional outcomes. learn more The majority of the seropositive cases had recent/concurrent CNS infections, suggesting triggered auto-immunity.

There is no consensus regarding the management and postoperative follow-up of non-functioning pituitary adenomas (NFAs) in the setting of recurrent or residual disease. Subsequent treatment options include continued follow-up, re-resection or radiotherapy. To address this gap and better understand current practice patterns, we surveyed neurosurgeons and radiation oncologists in Canada.

Neurosurgeons and radiation oncologists (ROs) across Canada were invited to complete a standardized online questionnaire. Summary statistics were computed, and Fisher's Exact tests were performed to assess significance. Qualitative analyses were performed through open and axial coding.

Thirty-three participants completed the questionnaires, with neurosurgeons representing a majority of respondents (

=20 vs

=13). When treating giant (>3cm) tumors, 90.9% of neurosurgeons in practice for less than 10years reported using an endoscopic approach, as compared to only 66.7% of neurosurgeons in practice for 10years of more. n the management of NFAs.We report the case of a 28-year-old man, diagnosed with a non-secreting, non-metastatic suprasellar germinoma treated with chemoradiation who developed, four months after completion of radiation therapy, multiple discrete demyelinating lesions mimicking multiple sclerosis (MS). The patient had no previous diagnosis of MS and the neuroimaging studies performed both at the time of diagnosis and after chemotherapy, pre-irradiation, showed no evidence of white matter lesions. He remained asymptomatic, with no focal neurological deficits. Biochemical analysis of the CSF was positive for the intrathecal synthesis of IgG with oligoclonal bands. Follow-up MRI six months later showed a spontaneous decrease in lesion size and resolution of associated inflammatory signs, with lesions remaining stable in number. We discuss the potential origin of these white matter lesions, which may correspond to MS-like late-delayed demyelination secondary to chemoradiation therapy, in a previously predisposed patient.