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Objective: Infectious myelopathy of any stage and etiology carries the potential for significant morbidity and mortality. This article details the clinical presentation, risk factors, and key diagnostic components of infectious myelopathies with the goal of improving the recognition of these disorders and guiding subsequent management., Latest Developments: Despite our era of advanced multimodal imaging and laboratory diagnostic technology, a causative organism often remains unidentified in suspected infectious and parainfectious myelopathy cases. To improve diagnostic capability, newer technologies such as metagenomics are being harnessed to develop diagnostic assays with a greater breadth of data from each specimen and improvements in infection identification. Conventional assays have been optimized for improved sensitivity and specificity., Essential Points: Prompt recognition and treatment of infectious myelopathy decreases morbidity and mortality. The key diagnostic tools include serologies, CSF analysis, and imaging; however clinical presentation, epidemiologic risk factors, and history of recent illness are all vital to making the proper diagnosis because current laboratory and imaging modalities are often inconclusive. The cornerstone of recommended treatment is targeted antimicrobials with appropriate immune modulation, surgical intervention, supportive care, and interdisciplinary involvement, all of which further improve outcomes for patients with infectious myelopathy., (Copyright © 2024 American Academy of Neurology.)

We describe the synthesis of trihydroxylated cyclohexane β-amino acids from (-)-shikimic acid, in their cis and trans configuration, and the incorporation of the trans isomer into a trans -2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of trans -2-aminocyclohexanecarboxylic acid. This means that the high degree of substitution of the cyclohexane ring of the new residue is compatible with the adoption of a stable helical secondary structure and opens opportunities for the design of more elaborate peptidic foldamers with oriented polar substituents at selected positions of the cycloalkane residues.

Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT. Serotonin decreases uncoupled respiration and reduces uncoupling protein 1 via the 5-HT 2B receptor. SERT inhibition by the selective serotonin reuptake inhibitor (SSRI) sertraline prevents uptake of extracellular serotonin, thereby potentiating serotonin's suppressive effect on brown adipocytes. Furthermore, we see that sertraline reduces BAT activation in healthy volunteers, and SSRI-treated patients demonstrate no 18 F-fluorodeoxyglucose uptake by BAT at room temperature, unlike matched controls. Inhibition of BAT thermogenesis may contribute to SSRI-induced weight gain and metabolic dysfunction, and reducing peripheral serotonin action may be an approach to treat obesity and metabolic disease., (© 2023. The Author(s).)

The synthesis of a range of loline alkaloids is reported. The C(7) and C(7a) stereogenic centers for the targets were formed by the established conjugate addition of lithium ( S )- N -benzyl- N -(α-methylbenzyl)amide to tert -butyl 5-benzyloxypent-2-enoate, ensuing enolate oxidation to give an α-hydroxy-β-amino ester, and then formal exchange of the resultant amino and hydroxyl functionalities (via the intermediacy of the corresponding aziridinium ion) to give an α-amino-β-hydroxy ester. Subsequent transformation gave a 3-hydroxyprolinal derivative which was converted to the corresponding N - tert -butylsulfinylimine. Mannich-type reaction with the enolate derived from O -Boc protected methyl glycolate then formed the remaining C(1) and C(2) stereogenic centers for the targets. The 2,7-ether bridge was formed by a displacement reaction, completing construction of the loline alkaloid core. Facile manipulations then gave a range of loline alkaloids, including loline itself.

Purpose: We evaluated the potential associations between the consumption of ultra-processed food (UPF) and the incidence of obesity among Uruguayan and Brazilian preschoolers., Design and Methods: We conducted a longitudinal analysis using data from preschool children from Uruguay and Brazil. The "Health, child development and nutritional survey" (ENDIS) was conducted in Uruguay in 2013-2014 and 2015-2016. The Brazilian survey (Pelotas 2015 Birth Cohort) has measures from 2017 and 2019. The main outcome measure was obesity defined as body mass index (BMI) for age and sex ≥ +3 z-scores. The score of UPF consumption was the main exposure measured. Multilevel crude and adjusted Poisson regressions were performed to estimate risk ratios and the respective 95% Confidence Intervals (95% CI)., Results: The overall incidence of obesity in this group of young Latin-American children with a mean age of 48 months was 4.1%. We observed a relationship between UPF and obesity with statistical significance (RR: 1.10 (95% CI, 1.02-1.18). Adjustment for weight at birth, age, sex, breastfeeding, country, and time between waves resulted in a similar relationship but lack of statistical significance., Conclusions: Whilst in this study we did not find strong evidence of an association between the incidence of obesity and the intake at baseline and currently of UPF, results suggest that higher UPF consumption is more favorable than reduced consumption for the development of obesity., Practice Implications: The present study reinforces the importance of nutrition education and more effective public policies for promoting healthier food choices in early childhood., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The first asymmetric synthesis of microgrewiapine C, a piperidine alkaloid isolated from Microcos paniculata , is reported. This synthesis prompted correction of the 1 H and 13 C NMR data for the natural sample of the alkaloid, which was achieved by reanalysis of the original spectra. The corrected data for the natural product were found to be identical to those of the synthetic sample prepared herein, thus confirming the structural and relative configurational assignment of microgrewiapine C. Although comparison of specific rotation values indicates that the (1 R ,2 S ,3 S ,6 S ) absolute configuration should be assigned to the alkaloid, consideration of potential common biosynthetic origins of microgrewiapine C and congeners suggests that further phytochemical investigations are warranted.