Synthesis and evaluation of Fmoc-amino esters and amides bearing a substrate like quaternary ammonium group as selective butyrylcholinesterase inhibitors.

The depletion of the neurotransmitter acetylcholine has been suggested to contribute to the reduced cognitive function observed in individuals suffering from neurodegenerative diseases such as Alzheimer's Disease (AD). For the two major cholinesterases, butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), increased BChE activity observed in individuals with AD has been suggested to deplete acetylcholine levels. To reduce acetylcholine degradation and help restore the pool of the neurotransmitter, specific and potent BChE inhibitors are sought. Our previous findings have identified 9-fluorenylmethoxycarbonyl (Fmoc) amino acid-based inhibitors as effective BChE inhibitors. The amino acid-based compounds offered the opportunity to survey a range of structural features to enhance interactions with the enzyme active site. As enzymes interact with features of their substrates, incorporation of substrate-like features was predicted to lead to better inhibitors. Specifically, incorporation of a trimethylammonium moiety to mimic the cationic group of acetylcholine may lead to increased potency and selectivity. To test this model, a series of inhibitors bearing a cationic trimethylammonium group were synthesized, purified, and characterized. While the Fmoc-ester derivatives inhibited the enzyme, additional experiments showed the compounds acted as substrates and were enzymatically hydrolyzed. Inhibition studies with the Fmoc-amide derivatives showed that the compounds do not act as substrates and selectively inhibit BChE with IC50 values in the 0.06-10.0 µM range. Computational docking studies suggest that the inhibitors can interact with cholinyl binding site and peripheral site. Overall, the results suggest that introducing substrate-like characteristics within the Fmoc-amino acid-based background increases their potency. The versatile and ready access to amino acid-based compounds offers an attractive system to further our understanding of the relative importance of protein-small molecule interactions while guiding the development of better inhibitors.

Automated production of 11 C-labeled carboxylic acids and esters via "in-loop" 11 C-carbonylation using GE FX synthesis modules.

An in-loop 11 C-carbonylation process for the radiosynthesis of 11 C-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables 11 C-carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide 11 C-carboxylic acids and esters in good to excellent radiochemical yields, high radiochemical purity, and excellent molar activity. The process has been fully automated using commercial radiochemistry synthesis modules, and application to clinical production is demonstrated via validated cGMP radiosyntheses of [11 C]bexarotene and [11 C]acetoacetic acid.

Awareness, social cognition, and commitment: Developing a social justice orientation in psychology training programs.

This study investigates how the awareness of social inequities and racism may serve as a foundation for psychology trainees' social justice self-efficacy beliefs, outcome expectations, interests, and commitment. Using the social-cognitive justice developmental framework proposed by Miller et al. (2009), a total of 222 participants were recruited from accredited applied psychology programs across the United States. Participants completed measures assessing their levels of two dimensions of critical consciousness: Egalitarianism and awareness of inequality (Diemer et al., 2017), their colorblind racial attitudes (Neville et al., 2000), and their social justice self-efficacy, outcome expectations, interests, and commitment (Miller et al., 2009). A hypothesized path model was fit to the data. Alternative models were also considered. Results indicated that participants who endorsed egalitarianism and were more aware of social inequities showed greater awareness of racism and, in turn, were more likely to endorse a higher orientation and commitment to social justice. Limitations and implications for future research and training are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Trusting in God: Religious and Spiritual Support in Mental Health Treatment Expectations in Mexico.

Religious and spiritual practices have been identified as a main source of mental health support for Latinxs to improve overall health and well-being. This qualitative secondary data analysis sought to elucidate how Mexican patients and family members engaged in religious and spiritual practices to help alleviate patients' experiences of mental illness. Three main findings are discussed: (1) positive religious coping such as entrusting God with one's suffering, consejos (i.e., emotional support and advice giving), and positive social supports through religious communities; (2) negative religious coping such as harmful views of God as punishing; and (3) indigenous healing practices such as engagement with curanderos (medicine doctor) and limpias (i.e., herb-based cleanses). The authors discuss these findings in the context of tensions between culturally sanctioned healing and the perception of psychotherapeutic effectiveness reported by Mexican patients and their family members. The authors also provide future directions for incorporating patients' religious and spiritual practices into multiculturally competent treatment.