Mandatory COVID-19 vaccination for healthcare workers: The experience of chaplains evaluating religious accommodation requests from coworkers.

Mandatory COVID-19 vaccination requirements for healthcare workers in the United States, instituted at the height of the pandemic to protect vulnerable patients and preserve the infrastructure of healthcare, nonetheless met with resistance by some members of the work force. As unprecedented numbers of employees sought religious accommodations, chaplain leaders were recruited by institutional leadership to adjudicate these requests, either alone or as part of a committee. This study reports results of a survey conducted from 6/1/2022 to 7/15/2022 with U.S. healthcare chaplains (n = 76) who were involved in the evaluation of coworker requests for religious exemption to the COVID-19 vaccine anytime during the pandemic until they accessed the survey. Chaplains were recruited online through national chaplaincy and ethics organizations. A mixed methods design facilitates integration of statistically significant associations with chaplains' in-depth reflections on their experience. Surveying the religious experts on the review committee affords a rare look into how the tension between the free exercise of religion in the workplace and the obligation to protect the public played out during the pandemic. The study further addresses a gap in research literature on the experience of chaplains during the pandemic and identifies unique features of moral injury experienced by a subset of healthcare providers. Chaplains largely perceived their involvement as promoting an ethical, informed process of review. Although all chaplains found this role stressful, high levels of meaning were protective against distress. Sources of distress identified included: ethical concern that granting exemptions would lead to the spread of the virus; inconsistencies in the review process; and, repeated exposure to coworkers' misunderstanding and political use of religious teachings. Featuring prominently in comments from chaplains was the difficulty navigating requests in the context of anti-science, anti-vaccine, and politically charged public discourse.

DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype.

The human promyelocytic HL60 cells acquired a neutrophilic phenotype after a 7- to 10-day DMSO treatment. Fc gammaRII was up-regulated. Fc gammaRI was also up-regulated by an additional IFN-gamma treatment. These cells are able to produce O2*- by NADPH oxidase activation in the presence of immune complexes or phorbol-12-myristate-13-acetate (PMA). A change of their PDE4 subtype profile was also observed: PDE4B was the predominant isoenzyme, PDE4D was down-regulated and PDE4A was no longer detectable. Additionally, the more NADPH oxidase was activated by PMA, the less PDE4A was expressed, suggesting that NADPH oxidase activity could be used as a surrogate marker of PDE4A down-regulation. Rolipram and Ariflo (cilomilast), two selective PDE4 inhibitors, dose-dependently inhibited receptor-coupled activation of superoxide. These results suggest that PDE4B is the main subtype involved in regulating superoxide induced by Fc gammaRs activation. Furthermore, these cells, expressing almost exclusively PDE4B subtype, could be useful to identify selective PDE4B inhibitors.

Synthesis and structure-activity relationships of 4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indoles: novel PDE4 inhibitors.

A novel series of benzodiazepine derivatives have been discovered as inhibitors of PDE4 enzymes. We have found that our compounds are selective versus other PDE enzymes, and that the activity can be modulated by specific structural modifications. One compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized Brown-Norway rats (compound 9, 5.1 mg/kg p.o.), moreover this compound is not emetic at 3 mg/kg i.v.

Purification, characterization and substrate specificity of rat pancreatic elastase II.

A somatostatin-14-degrading activity has been purified to homogeneity from rat pure pancreatic juice. This proteinase was concentrated more than 350-fold in a four-step procedure including ion-exchange and gel filtration. The final preparation contained a single protein with a molecular weight (M(r)) of approx. 29,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The determination of its NH2-terminal sequence led us to conclude that the purified proteinase corresponds to the rat pancreatic elastase II predicted from the cDNA clone isolated by MacDonald in 1982. This anionic proteinase exhibits an isoelectric point of 5.6 and does not contain any carbohydrate moieties in its structure. The proteinase is sensitive to the trypsin inhibitors soybean trypsin inhibitor and N alpha-tosyl-L-lysine-chloromethyl ketone and also to 3,4-dichloroisocoumarin, a general elastase inhibitor. The cleavage products obtained after hydrolysis of somatostatin-14 by the purified elastase, were separated by reversed phase high performance liquid chromatography and identified by amino-acid analysis. The primary hydrolysis was trypsin-like and consisted in an opening of the cyclic structure of somatostatin-14 after the Lys-9 residue leading to the formation of a Y-shaped peptide with the same amino-acid composition as the native peptide. The initial 'trypsin-like specificity' was not observed during the secondary hydrolysis of the Y-shaped peptide; indeed the proteinase seemed more specific for a certain motif in the native peptide rather than for a specific class of amino acid, this last kind of selectivity is commonly observed with trypsin and chymotrypsin. In order to establish that the proteinase possesses an extended recognition site on the substrate rather than a specificity for a class of amino acid, the substrate specificity of the rat pancreatic elastase II was investigated with a series of para-nitroanilide peptides. The proteinase exhibits a large specificity involving peptide chain of at least four amino acids with a preference for bulky residue in P1 or P2. The Km values of 89 microM and 1567 microM obtained for somatostatin-14 and Suc-Ala-Ala-Pro-Met-pNA, respectively, indicate that elastase II has a greater affinity for the natural substrate than for synthetics. This last observation along with the substrate specificity of the proteinase leads us to propose that elastase II could be specifically involved in the regulation of biological functions of somatostatin-14 in the gastrointestinal tract.