Comparative Embryo Development Outcomes following Extending Embryo Culture to Day 6: A Retrospective Cohort Study.

BACKGROUND: Past studies have shown that culturing slow-growing embryos from day 5 to day 6 may increase vitrification yield. This study aims to evaluate if the proportion of embryos eligible for vitrification increases by growing embryos not vitrified by day 5 to day 6. MATERIALS AND METHODS: In this retrospective cohort study, a Canadian tertiary-care clinic-based cohort was identified between August 2019 and December 2020. In vitro fertilization (IVF) cycles involving autologous oocytes with at least one viable day 5 embryo were selected for inclusion. We compared embryo developmental outcomes of IVF cycles performed before and after an embryo cryopreservation policy change. Prior to March 2020, good-quality day 5 blastocysts of any stage were eligible for vitrification, and after that date, good-quality expanded blastocysts on either day 5 or day 6 were eligible. The primary outcome is the comparative proportion of embryos eligible for vitrification. The secondary outcome is to identify embryo, maternal and cycle factors that are predictive of day 6 vitrification. RESULTS: A total of 3,438 viable embryos across 679 consecutive IVF cycles were included in this study. After the policy change, we found similar mean proportions of blastocysts eligible for cryopreservation (46.9% per IVF cycle in group 2 vs. 44.4% in group 1, mean difference 0.025, 95% confidence interval -0.021 to 0.071, P=0.28). The mean number of cryopreserved embryos were significantly higher in group 2 (mean 2.2 vs. 1.7 embryos, P=0.007). Factors that predicated an embryo's progression to day 6 included: younger age of egg provider, presence of an early blastocyst on day 5, and cycles involving surgically-retrieved sperm. CONCLUSION: A cryopreservation policy change to include good-quality full and expanded day 6 blastocysts while avoiding to vitrify early blastocysts on day 5 yielded comparable proportions of embryos eligible for vitrification per IVF cycle.

Examining the Collateral Effects of Reducing Voice Level on Vocal Stereotypy and Functional Speech.

The current study examined the collateral effects of an antecedent intervention for decreasing speech volume on vocal stereotypy. After teaching the participant to use a conversational voice level by providing visual feedback from a decibel meter app, conversational voice levels were differentially reinforced in the presence of a green card. Differential effects in voice magnitude during a green-card condition and a no-card condition were demonstrated using an alternating-treatments design. Results showed a decrease in volume of speech during the green-card condition, an overall decrease in vocal stereotypy, and a decrease to zero levels in loud stereotypical vocalizations. The implications of these findings on the treatment of vocal stereotypy are discussed.

Dihydroquinazolines enhance 20S proteasome activity and induce degradation of α-synuclein, an intrinsically disordered protein associated with neurodegeneration.

Aggregates or oligomeric forms of many intrinsically disordered proteins (IDPs), including α-synuclein, are hallmarks of neurodegenerative diseases, like Parkinson's and Alzheimer's disease, and key contributors to their pathogenesis. Due to their disordered nature and therefore lack of defined drug-binding pockets, IDPs are difficult targets for traditional small molecule drug design and are often referred to as "undruggable". The 20S proteasome is the main protease that targets IDPs for degradation and therefore small molecule 20S proteasome enhancement presents a novel therapeutic strategy by which these undruggable IDPs could be targeted. The concept of 20S activation is still relatively new, with few potent activators having been identified thus far. Herein, we synthesized and evaluated a library of dihydroquinazoline analogues and discovered several promising new 20S proteasome activators. Further testing of top hits revealed that they can enhance 20S mediated degradation of α-synuclein, the IDP associated with Parkinson's disease.

One-Pot Tandem Assembly of Amides, Amines, and Ketones: Synthesis of C4-Quaternary 3,4- and 1,4-Dihydroquinazolines.

A multicomponent tandem assembly procedure for the synthesis of diverse C4-quaternary 3,4-dihydroquinazolines from amides, amines, and ketones has been developed. The one-pot reaction involves successive triflic anhydride mediated amide dehydration, ketimine addition, and Pictet-Spengler-like cyclization processes and affords products in up to 92% yield. Conversion of 3,4-dihydroquinazolines to the corresponding 1,4-dihydroquinazolines via a two-step N1 dealkylation and regioselective N3 functionalization protocol, including computational rationale for the observed regioselectivity, is also described.

Triflic anhydride mediated synthesis of 3,4-dihydroquinazolines: a three-component one-pot tandem procedure.

A one-pot three-component tandem reaction involving a key Pictet-Spengler-like annulation step has been developed, providing an efficient method for the synthesis of 3,4-dihydroquinazolines in moderate to good yields from amides, aldehydes, and amines. The multicomponent triflic anhydride mediated reaction tolerates the installation of numerous functional groups, affording extensive diversity about the heterocyclic scaffold.

Do prelicensure nursing students' backgrounds impact what they notice and interpret about patients?

BACKGROUND: Academic educators are challenged to foster the development of clinical judgment in diverse learners. The impact of nursing students' backgrounds on clinical judgment has not previously been studied. AIMS: SAMPLE: Prelicensure/preregistration students, representing three international English-speaking programs in 3 countries, comprised the sample (N = 532). All were enrolled in the first course in which perioperative content was taught. DATA COLLECTION: An online learning activity was designed to elicit responses to a simulated case study of an expert nurse role model caring for an older adult patient experiencing delirium several days post-operatively. DATA ANALYSIS: Dyads of coders did three rounds of coding. Logistic and multinomial logistic regression models used background variables to look for patterns in student responses. FINDINGS: The data strongly suggest that background variables impact clinical judgment, however, not in interpretable patterns. CONCLUSION: Nurse educators must acknowledge that prelicensure students' backgrounds impact their clinical judgment and assist them to learn to think like nurses.