A General Strategy to Install Amidine Functional Groups Along the Peptide Backbone.

Amidines are a structural surrogate for peptide bonds, yet have received considerably little attention in peptides due to limitations in existing methods to access them. The synthetic strategy developed in this study represents the first robust and general procedure for the introduction of amidines into the peptide backbone. We exploit and further develop the utility and efficiency of thioimidate protecting groups as a means to side-step reactivity that ultimately renders existing methods unsuitable for the installation of amidines along the main-chain of peptides. This work is significant because it describes a generally applicable path to access unexplored peptide designs and architectures for new therapeutics made possible by the unique properties of amidines.

Deprotection Strategies for Thioimidates during Fmoc Solid-Phase Peptide Synthesis: A Safe Route to Thioamides.

Thioamides are important biophysical probes of peptide folding but are prone to α-C epimerization during Fmoc solid-phase peptide synthesis. The stereochemical integrity of thioamide-containing peptides can be dramatically improved by protecting the thioamide as a thioimidate during synthesis. A drawback of this approach, however, is that once synthesis of the peptide is complete, regeneration of the thioamide requires the toxic, corrosive, and flammable gas H2S. This work examines several approaches to supplant H2S as a deprotection reagent in favor of a safer and more convenient alternative. Ultimately, a new application of the 4-azidobenzyl protecting group to thioamides was found to provide the most suitable means of both protection of α-C stereochemistry and conversion back to thioamide.

Knowledge, Perception, and Use of Cannabis Therapy in Patients with Inflammatory Bowel Disease.

OBJECTIVE: In 2017, the government of Puerto Rico legalized medical cannabis for several conditions including Crohn's disease (CD). There is little information about cannabis use in this population. This study aimed to develop a demographic characterization and evaluate patient perception on cannabis use for Inflammatory Bowel Disease (IBD) at the University of Puerto Rico Center for Inflammatory Bowel Diseases. METHODS: One hundred patients of ages 21 or older with a confirmed diagnosis of IBD were recruited to complete a voluntary anonymous questionnaire. RESULTS: 27% of the surveyed participants reported use of cannabis. Of these, 39% reported moderate knowledge and 53% reported little to no knowledge of medical cannabis. The majority did not discuss cannabis use with their physician (78%), and most saw improvement of their symptoms (68%). CONCLUSION: Cannabis is frequently considered by patients as a treatment option for IBD but most have limited knowledge about its use. The low number of patients that discuss cannabis use with their physician suggests the need for physician awareness of unreported use. It should also lead to the development of strategies for patient orientation regarding the uses, properties, and expectations of cannabis as a therapy.

A Bottom-Up Approach To Preserve Thioamide Residue Stereochemistry during Fmoc Solid-Phase Peptide Synthesis.

Thioamides are useful biophysical probes for the study of peptide structure and folding. The α-C stereochemistry of thioamide amino acids, however, is easily epimerized during solid-phase peptide synthesis (SPPS), which limits the sequence space that is available to thioamide incorporation. This work demonstrates that the α-C stereochemistry of thioamides can be reversibly protected in a manner that is compatible with the standard methodology of SPPS to enable the facile implementation of thioamide probes.

Molecular and phenotypic analysis of a working seed lot of yellow fever virus 17DD vaccine strain produced from the secondary seed lot 102/84 with an additional passage in chicken embryos.

Over the last 17 years, the yellow fever (YF) 17DD vaccine secondary seed lot 102/84 was used to produce many million doses of vaccine but it was recently used up. In the absence of other lots at the same passage level a large vaccine batch produced from 102/84 was turned into a new working seed. This new seed was characterized with regard to attenuation in the recommended internationally accepted monkey neurovirulence test (MNVT) using the 102/84 virus as reference. All rhesus monkeys (Macaca mulatta) developed limited viremia and comparable neutralizing antibody titers. Clinical evaluation and histological examination of the central nervous system (CNS) according to WHO criteria for acceptability gave consistent data that demonstrated an attenuated phenotype for the YF 17DD 993FB013Z (13Z) vaccine batch. It is concluded that the additional chicken embryo passage did not lead to any genetic change and the new working seed virus retained its attenuation for monkeys comparable to the 102/84 reference virus.

Manifestaçöes articulares nas viroses exantemáticas / Joint complaints in exanthematic diseases

A frequência de manifestaçöes articulares foi avaliada em 251 pacientes com diagnóstico clínico e laboratorial (detecçäo de IgM por ensaio imunoenzimático) de virose exantemática. As artropatias (artralgia e/ou artrite) foram mais observadas nos casos de dengue (49 por cento) e de rubéola (38,2 por cento) do que naqueles com parvovirose humana (30 por cento) e sarampo (28,1 por cento). Com exceçäo do sarampo, as artropatias predominaram nos adultos (>/= 15 anos de idade), sendo tal diferença estatisticamente signinficativa. A ocorrência maior de artropatias em adultos foi mais evidente nos pacientes com parvovirose (75 por cento), rubéola (65 por cento) e dengue (57,7 por cento) do que naqueles com sarampo (31 por cento). As queixas articulares também predominaram nos pacientes do sexo feminino para todas as viroses avaliadas. Os resultados encoontrados demonstram o frequente acometimento articular nas doenças estudadas, e indicam a necessidade de comprovaçäo laboratorial para o diagnóstico diferencial entre elas