Our findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress-induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug-like action on the enteric nervous system.

The frequency with which diethylstilbestrol induces neoplastic transformation and somatic mutation was measured concomitantly in Syrian hamster embryo cells. While diethylstilbestrol was as active as benzo[a]pyrene in inducing transformation, it failed to induce mutations at two conventionally studied loci. These results suggest that diethylstilbestrol may transform cells in the absence of gene mutations.

A class of dominant lethal mutations in the dnaB (replicative helicase) gene of Salmonella typhimurium is described. The mutated genes, when present on multicopy plasmids, interfered with colony formation by Escherichia coli host strains with a functional chromosomal dnaB gene. The lethal phenotype was expressed specifically in supE (glutamine-inserting) host strains and not in Sup' strains, because the mutant genes, by design, also possessed an amber mutation derived from a glutamine codon. Mutations located at 11 sites by deletion mapping and DNA sequence analysis varied in the temperature dependence and severity of their lethal effects. None of the mutations complemented a dnaB(Ts) host strain at high temperature (42°C). Therefore, these nonfunctional DnaB proteins must engage some component(s) of the DNA replication machinery and inhibit replication. These mutations are predicted to confer limited, specific defects in either the catalytic activity of DnaB or the ability of DnaB to interact with one of its ligands such as DNA, nucleotide, or another replication protein. The variety of mutant sites and detailed phenotypes represented in this group of mutations may indicate the operation of more than one specific mechanism of lethality.The DnaB protein of Escherichia coli and a structurally similar (38) and functionally interchangeable (25) protein from Salmonella typhimurium are helicases (22) whose actions at replication origins and replication forks involve multiple overlapping functions. These functions include assembly into a replication complex at a bacterial origin that is dependent on DnaA and DnaC proteins (10); ATP binding and DNA-dependent ATP hydrolysis (2, 29, 33); helicase action associated with nucleotide hydrolysis, 5' to 3' migration on single-stranded DNA, and movement of a replication fork (9, 22); and interaction with primase (1, 4, 22). In addition, DnaB monomers associate to form hexamers, presumably the active form in vivo (7,32), and DnaB interacts with other proteins during replication of bacteriophages X and (X174 and plasmid ColEl (5,6,13,14,23,26).How is the DnaB protein organized to carry out these functions? Some insight into this question has been gained from analysis of fragments generated by limited trypsin digestion of wild-type DnaB of E. coli (29). In that study (29) two protease-stable domains (residues 15 to 125/127 and 172 to 470) were identified in the 470-residue protein. The carboxyl-terminal domain exhibited nucleotide binding and single-stranded DNA-dependent nucleotide hydrolysis and was able to self-oligomerize. A conformational change in DnaB associated with the hydrolysis of ATP to ADP (3) was inferred from the much greater sensitivity of the internal trypsin cleavage sites in the presence of ADP than in the presence of the ATP analog adenosine-5'-O-(3'-thiotriphosphate) (ATP-yS) (2). The isolated domains, either alone or in combination, exhibited no replication activity.Another clue about the functional organization of DnaB comes from the similarity at the amino ...

AIMTo investigate the capacity of Saccharomyces cerevisiae (S. cerevisiae) and Saccharomyces boulardii (S. boulardii) yeasts to reverse or to treat acute stress-related intestinal dysmotility.METHODSAdult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae, S. boulardii, or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls.RESULTSS. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P < 0.001 and jejunal transit frequency (Hz) from 0.032 ± 0.008 to 0.016 ± 0.005, P < 0.001. Restraint stress increased colonic transit velocity (mm/s) from 0.864 ± 0.183 to 1.432 ± 0.329, P < 0.001 and frequency to a lesser degree. Luminal application of S. boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P < 0.001 and 1.516 ± 0.263 to 1.036 ± 0.21, P < 0.001, respectively. S. cerevisiae also had therapeutic effects on the stressed gut, but was most apparent in the jejunum. S. cerevisiae increased PCC velocity in the stressed jejunum from 1.763 ± 0.397 to 2.017 ± 0.48, P = 0.0031 and PCC frequency from 0.016 ± 0.009 to 0.027 ± 0.007, P < 0.001. S. cerevisiae decreased colon PCC velocity from 1.647 ± 0.187 to 1.038 ± 0.222, P < 0.001. Addition of S. boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar capacity.CONCLUSIONThere is a potential therapeutic role for S. cerevisiae and S. boulardii yeasts and their supernatants in the treatment of acute stress-related gut dysmotility.

Objective: Traditional gender norms and expectations may disproportionately constrain in-home palliative care received by women. This scoping review aims to canvass and evaluate the literature on gender disparities in end of life care and explore relevant themes that could inform future research and practice. Methods: A systematic search of MEDLINE, OVID, COCHRANE, and EMBASE was conducted using MeSH terms palliative care, palliative medicine, terminal care, or hospice care, combined with gender equity, sex factors, sexism, or gender disparities. Articles were limited to those in English (2010 to 2021), focusing on end of life care, gender roles, patients, and caregivers. Results: Of 624 articles identified, 15 met inclusion criteria for critical appraisal using the AMSTAR checklist for systematic reviews and NICE guidelines for quantitative and qualitative studies. Most studies were of poor to moderate quality. Thematic analyses identified 6 major themes related to gender disparities: living situation, symptom experience, care context, care preferences, caregiving, and coping strategies. Conclusion: Larger scale research of better quality is needed to fully characterize gender disparities in end of life care and understand how physicians might mitigate these disparities by building awareness of personal gender biases, providing support to families, educating them, and initiating care discussions that overturn traditional and stereotypic gendered expectations.