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Peptides, polymers of amino acids, comprise a vital and expanding therapeutic approach. Their rapid degradation by proteases, however, represents a major limitation to their therapeutic utility and chemical modifications to native peptides have been employed to mitigate this weakness. Herein, we describe functionalized thiocarbazate scaffolds as precursors of aza-amino acids, that, upon activation, can be integrated in a peptide sequence to generate azapeptides using conventional peptide synthetic methods. This methodology facilitates peptide editing-replacing targeted amino acid(s) with aza-amino acid(s) within a peptide-to form azapeptides with preferred therapeutic characteristics (extending half-life/bioavailability, while at the same time typically preserving structural features and biological activities). We demonstrate the convenience of this azapeptide synthesis platform in two well-studied peptides with short half-lives: FSSE/P5779, a tetrapeptide inhibitor of HMGB1/MD-2/TLR4 complex formation, and bradykinin, a nine-residue vasoactive peptide. This bench-stable thiocarbazate platform offers a robust and universal approach to optimize peptide-based therapeutics., (© 2022. The Author(s).)

Palauan foodways have changed significantly over the last 100 years. Current nutritional norms in Palau have led to increased prevalence of nutrition-based noncommunicable disease. While generational change in Palauan foodways in the decades immediately following World War II has been documented, less attention has been paid to change since national independence. Parents, teachers, and students at Palauan elementary schools participated in focus groups designed to advance understanding of the current state of Palauan nutrition across generations at home, school, and elsewhere (including after-school snacks and ritual events). We document these perspectives and share Palauan ideas for improving local nutrition.

Purpose: Preterm birth (PTB), a pressing issue for US maternal-child health, disproportionately impacts women in Appalachia. Transvaginal ultrasound (TVU) cervical length (CL) screening is the most accurate PTB risk predictor but remains underutilized. This study characterizes the knowledge, attitudes and beliefs of patients with prior PTB concerning PTB prevention efforts and TVU CL screening., Methods: Participants were recruited from community-based health centers in Appalachian Kentucky. Semi-structured interviews and likert-scale surveys were conducted with 22 pregnant women with a history of spontaneous PTB. Methods for data collection were guided by the Consolidated Framework for Implementation Research (CFIR)., Results: Most participants reported that TVU was uncomfortable, but none refused it. Most women were able to articulate the benefits of TVU, but several had concerns about its safety in pregnancy. Participants suggested that pregnant women receive more PTB education and self-advocate. They urged providers to take patient concerns seriously, and better educate patients on PTB risks and TVU safety., Discussion: Our study contributes crucial insights about the experience of a vulnerable population as it pertains to PTB prevention and the uptake of TVU CL screening. Our findings emphasize the need for increased efforts to better educate patients on the impact of prematurity and the safety and benefits of TVU CL screening as an evidence-based strategy for PTB prevention., (Copyright © 2021. Published by Elsevier Inc.)

Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis specific member of the DEAD-box family of RNA helicases expressed in meiotic and haploid germ cells which plays an essential role in spermatogenesis. There are two species of GRTH the 56 kDa non-phospho and 61 kDa phospho forms. Our early studies revealed a missense mutation (R242H) of GRTH in azoospermic men that when expressed in COS1-cells lack the phospho-form of GRTH. To investigate the role of the phospho-GRTH species in spermatogenesis, we generated a GRTH knock-in (KI) transgenic mice with the R242H mutation. GRTH-KI mice are sterile with reduced testis size, lack sperm with spermatogenic arrest at round spermatid stage and loss of the cytoplasmic phospho-GRTH species. Electron microscopy studies revealed reduction in the size of chromatoid bodies (CB) of round spermatids (RS) and germ cell apoptosis. We observed absence of phospho-GRTH in the CB of RS. Complete loss of chromatin remodeling and related proteins such as TP2, PRM2, TSSK6 and marked reduction of their respective mRNAs and half-lives were observed in GRTH-KI mice. We showed that phospho-GRTH has a role in TP2 translation and revealed its occurrence in a 3' UTR dependent manner. These findings demonstrate the relevance of phospho-GRTH in the structure of the chromatoid body, spermatid development and completion of spermatogenesis and provide an avenue for the development of a male contraceptive., (Published by Oxford University Press 2019.)

Purpose: Factors associated with the publication of scholarly articles by pharmacists were evaluated., Methods: A Web-based survey was distributed to all pharmacists who published at least one scholarly article in selected pharmacy and medical journals in 2008. All scholarly works published in the American Journal of Health-System Pharmacy, Annals of Pharmacotherapy, and Pharmacotherapy during the study period were categorized by study design using a predetermined algorithm. A secondary group of pharmacists who published in at least 1 of 10 selected medical journals during the study period was also evaluated to identify any differences between those who published in pharmacy versus medical journals., Results: The final number of usable responses was 254, for an adjusted response rate of 72.9%. Factors identified as the most helpful for facilitating publication efforts included time allotment, mentorship, and collaborative efforts. "Lack of time" was reported as the most important barrier to publication. The majority of respondents (73%, n = 182) published their first article during a training program (academic program, residency, or fellowship). Of the 468 scholarly works published in the selected pharmacy journals during the study period, review articles were most common (38.7%, n = 177)., Conclusion: The most influential factors on the publication efforts by pharmacists were time allotment, collaboration between pharmacy colleagues and within multidisciplinary teams, and training in research methods and scientific writing. Introduction to the publication process during training programs appeared to influence future propensity toward scholarly participation. Review and descriptive articles were the most frequently published types of articles in the pharmacy literature.

Background: Risks associated with contraindicated drug-drug interaction alerts (CDDIAs) should always outweigh benefits. Misclassified CDDIAs should be eliminated., Objective: To review CDDIAs and determine if they are contraindicated according to Food and Drug Administration-approved product labeling and if there are circumstances in which contraindicated interactions are acceptable., Methods: A cross-sectional observational and quality improvement study was conducted over two 1-year periods. The 20 most common CDDIAs from May 2007 to May 2008 and all CDDIAs from April 2008 to April 2009 were collected at a large teaching hospital. Horizon Meds Manager used First DataBank as the knowledge base for decision support. Interactions were deemed truly contraindicated if listed in the contraindications section of the labeling of at least one of the interacting drugs. Alerts were grouped by drug and pharmacologic class to evaluate the evidence supporting the relevance of these interactions. An expert panel determined when an alert was misclassified. A medical advisory committee determined whether a contraindicated drug-drug combination was acceptable., Results: Twelve (60%) of the most common 20 contraindicated interaction pairs from 2007 to 2008 were inappropriately classified. Half of the alerts were not truly contraindicated. The 8 truly contraindicated drug-drug pairs were ketorolac and other nonsteroidal antiinflammatory drugs or oral solid potassium products and anticholinergics. Half of these interactions were subsequently deemed acceptable under specific circumstances. Similar results were found in the second year, with only 55.1% of all CDDIAs being truly contraindicated despite eliminating some of the alerts that were misclassified in the first year. Nearly three fourths of legitimate CDDIAs were deemed acceptable under specific circumstances., Conclusions: Most contraindicated drug-drug interaction alerts from a commercial knowledge base were inappropriately categorized and could be downgraded. Some contraindicated drug combinations are permissible under specific circumstances. Alerts suggesting that certain drugs should never be used together, but their use together is sometimes acceptable, contribute to alert fatigue.

A polysaccharide apparently identical with glycogen has been extracted from sweet corn.