Paraherquamide E

In the title compound, C28H35N3O4, also known as 14-de­oxy­paraherquamide A,the two pyrrolidine rings adopt envelope conformations. The piperazine ring of the diaza­bicyclo­[2.2.2]octan-3-one unit adopts a boat conformation whereas the two piperidine rings are in distorted boat conformations. Intra­molecular C—H⋯O hydrogen bonds are observed. In the crystal, the mol­ecules are linked into chains along the b axis by inter­molecular N—H⋯O hydrogen bonds

Training in the Management of Psychobehavioral Conditions: A Needs Assessment Survey of Emergency Medicine Residents

ObjectiveMental health–related ED visits are increasing. Despite this trend, most emergency medicine (EM) residency programs devote little time to psychiatry education. This study aimed to identify EM residents’ perceptions of training needs in emergency psychiatry and self‐confidence in managing patients with psychobehavioral conditions.MethodsA needs assessment survey was distributed to residents at 15 Accreditation Council for Graduate Medical Education–accredited EM programs spanning the U.S. Survey items addressed amount and type of training in psychiatry during residency, perceived training needs in psychiatry, and self‐confidence performing various clinical skills related to emergency psychiatric care. Residents used a 5‐point scale (1 = nothing; 5 = very large amount) to rate their learning needs in a variety of topic areas related to behavioral emergencies (e.g., medically clearing patients, substance use disorders). Using a scale from 0 to 100, residents rated their confidence in their ability to independently perform various clinical skills related to emergency psychiatric care (e.g., differentiating a psychiatric presentation from delirium).ResultsOf the 632 residents invited to participate, 396 (63%) responded. Twelve percent of respondents reported completing a psychiatry rotation during EM residency. One of the 15 participating programs had a required psychiatry rotation. Residents reported that their program used lectures (56%) and/or supervised training in the ED (35%) to teach residents about psychiatric emergencies. Most residents reported minimal involvement in the treatment of patients with psychiatric concerns. The majority of residents (59%) believed that their program should offer more education on managing psychiatric emergencies. Only 14% of residents felt “quite” or “extremely” prepared to treat psychiatric patients. Overall, residents reported the lowest levels of confidence and highest need for more training related to counseling suicidal patients and treating psychiatric issues in special populations (e.g., pregnant women, elderly, and children).ConclusionsMost EM residents desire more training in managing psychiatric emergencies than is currently provided.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152005/1/aet210377-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152005/2/aet210377.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152005/3/aet210377_am.pd

In Vivo Systematic Analysis of Candida albicans Zn2-Cys6 Transcription Factors Mutants for Mice Organ Colonization

The incidence of fungal infections in immuno-compromised patients increased considerably over the last 30 years. New treatments are therefore needed against pathogenic fungi. With Candida albicans as a model, study of host-fungal pathogen interactions might reveal new sources of therapies. Transcription factors (TF) are of interest since they integrate signals from the host environment and participate in an adapted microbial response. TFs of the Zn2-Cys6 class are specific to fungi and are important regulators of fungal metabolism. This work analyzed the importance of the C. albicans Zn2-Cys6 TF for mice kidney colonization. For this purpose, 77 Zn2-Cys6 TF mutants were screened in a systemic mice model of infection by pools of 10 mutants. We developed a simple barcoding strategy to specifically detect each mutant DNA from mice kidney by quantitative PCR. Among the 77 TF mutant strains tested, eight showed a decreased colonization including mutants for orf19.3405, orf19.255, orf19.5133, RGT1, UGA3, orf19.6182, SEF1 and orf19.2646, and four an increased colonization including mutants for orf19.4166, ZFU2, orf19.1685 and UPC2 as compared to the isogenic wild type strain. Our approach was validated by comparable results obtained with the same animal model using a single mutant and the revertant for an ORF (orf19.2646) with still unknown functions. In an attempt to identify putative involvement of such TFs in already known C. albicans virulence mechanisms, we determined their in vitro susceptibility to pH, heat and oxidative stresses, as well as ability to produce hyphae and invade agar. A poor correlation was found between in vitro and in vivo assays, thus suggesting that TFs needed for mice kidney colonization may involve still unknown mechanisms. This large-scale analysis of mice organ colonization by C. albicans can now be extended to other mutant libraries since our in vivo screening strategy can be adapted to any preexisting mutants

Antimicrobial Natural Products

Although the first antibiotic, penicillin, was discovered in 1928 from a microbial natural source (a mould, Penicillium notatum), there is earlier evidence of using natural materials including moulds and herbs for the treatment of infections. Following the serendipitous discovery of penicillin by Alexander Fleming, there have been hundreds of antibiotics (natural, semisynthetic and synthetic) discovered for clinical uses. However, the pathogenic organisms have developed resistances to existing antibiotics though various mechanisms. Such antibiotic resistance or antimicrobial resistance (AMR) is a critical problem of today’s healthcare system urging the development of new antibiotics. This chapter has primarily focused into antimicrobial compounds developed through natural routes that are currently available as antibiotics for clinical uses and/or are at various developmental stages within the drug development pipeline for potential treatment of minor and life threatening infections. The chapter also provides an overview on the catastrophic problem of antimicrobial resistance, its causes, how it spreads as well as modes of developing antimicrobial resistance (AMR)

Fungal Origins of the Bicyclo[2.2.2]diazaoctane Ring System of Prenylated Indole Alkaloids

Over eight different families of natural products, consisting of nearly seventy secondary metabolites, which contain the bicyclo[2.2.2]diazaoctane ring system, have been isolated from various Aspergillus, Penicillium, and Malbranchea species. Since 1968, these secondary metabolites have been the focus of numerous biogenetic, synthetic, taxonomic, and biological studies, and, as such, have made a lasting impact across multiple scientific disciplines. This review covers the isolation, biosynthesis, and biological activity of these unique secondary metabolites containing the bridging bicyclo[2.2.2]diazaoctane ring system. Furthermore, the diverse fungal origin of these natural products is closely examined and, in many cases, updated to reflect the currently accepted fungal taxonomy