Clinical trials to address the COVID-19 public health emergency have broadly excluded pregnant people from participation, illustrating a long-standing trend of clinical trial exclusion that has led ...to a clear knowledge gap and unmet need in the treatment and prevention of medical conditions experienced during pregnancy and of pregnancy-related conditions. Drugs (includes products such as drugs, biologics, biosimilars and vaccines) approved for a certain medical condition in adults are also approved for use in pregnant adults with the same medical condition, unless contraindicated for use in pregnancy. However, there are limited pregnancy-specific data on risks and benefits of drugs in pregnant people, despite their approval for all adults. The United States Food and Drug Administration–approved medical products are used widely by pregnant people, 90% of whom take at least 1 medication during the course of their pregnancy despite there being sparse data from clinical trials on these products in pregnancy. This overall lack of clinical data precludes informed decision-making, causing clinicians and pregnant patients to have to decide whether to pursue treatment without an adequate understanding of potential effects. Although some United States Food and Drug Administration initiatives and other federal efforts have helped to promote the inclusion of pregnant people in clinical research, broader collaboration and reforms are needed to address challenges related to the design and conduct of trials that enroll pregnant people, and to forge a culture of widespread inclusion of pregnant people in clinical research. This article summarizes the scientific, ethical, and legal considerations governing research conducted during pregnancy, as discussed during a recent subject matter expert convening held by the Duke-Margolis Center for Health Policy and the United States Food and Drug Administration on this topic. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.
Solid-phase microextraction coupled to gas chromatography and mass spectrometry has been applied as a simple alternative method for the analysis of essential oil directly from lavender intact ...flowering spikes and genuine oils. All recognised major oil constituents were detected by this procedure, with results comparable to those given by a conventional method (organic solvent extraction). Distinctive chromatographic profiles were found for various species.
Escherichia coli O157:H7 in microbial flora of sheep Kudva, I.T. (University of Idaho, Moscow, ID.); Hatfield, P.G; Hovde, C.J
Journal of Clinical Microbiology,
02/1996, Letnik:
34, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We found naturally occurring, potentially virulent Escherichia coli O157:H7 strains in sheep. The incidence of E. coli O157:H7 was transient and ranged from 31% of sheep in June to none in November. ...The use of a sensitive culture technique and the choice of the proper sampling season were both essential for detecting this bacterium in sheep. DNA hybridizations showed that 80% of the E. coli O157:H7 isolates had at least two of the Shiga-like toxin types I or II or the attaching-effacing lesion genes
The tertiary structure of the TC5b miniprotein is stabilized by inter-residue interactions of the Trp-cage, which is composed of a Tyr and several Pro residues surrounding a central Trp residue. The ...interactions include Ar−Ar (aromatic side-chain−aromatic side-chain), Ar−NH (aromatic side-chain−backbone amide), and CH−π (aromatic side-chain−aliphatic hydrogen) interactions. In the present work, the strength of the weakly polar interactions found in the TC5b miniprotein was quantified using all of the available 38 NMR structures (1L2Y) from the Protein Data Bank with DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory and molecular fragmentation with capping of the partial structures. The energies of interaction between the individual residues of the Trp-cage range between −5.85 ± 1.41 and −21.30 ± 0.88 kcal mol-1, leading to a significant total structural stabilization energy of −52.13 ± 2.56 kcal mol-1 of which about 50% is from the weakly polar interactions. Furthermore, the strengths of the individual weakly polar interactions are between −2.32 ± 0.17 and −2.93 ± 0.12 kcal mol-1 for the CH−π interactions, between −2.48 ± 0.97 and −3.09 ± 1.02 kcal mol-1 for the Ar−NH interaction and −2.74 ± 1.06 kcal mol-1 for the Ar−Ar interaction.
The isolation and characterization of Escherichia coli O157:H7 and non-O157 Shiga toxin-producing E. coli (STEC) strains from sheep are described. One flock was investigated for E. coli O157:H7 over ...a 16-month period that spanned two summer and two autumn seasons. Variation in the occurrence of E. coli O157:H7-positive sheep was observed, with animals being culture positive only in the summer months but not in the spring, autumn, or winter. E. coli O157:H7 isolates were distinguished by pulsed-field gel electrophoresis (PFGE) of chromosomal DNA and toxin gene restriction fragment length polymorphism (RFLP) analysis. Ten PFGE patterns and five RFLP patterns, identified among the isolates, showed that multiple E. coli O157:H7 strains were isolated from one flock, that a single animal simultaneously shed multiple E. coli O157:H7 strains, and that the strains shed by individuals changed over time. E. coli O157:H7 was isolated only by selective enrichment culture of 10 g of ovine feces. In contrast, strains of eight STEC serotypes other than O157:H7 were cultured from feces of sheep from a separate flock without enrichment. The predominant non-O157 STEC serotype found was O91:NM (NM indicates nonmotile), and others included O128:NM, O88:NM, O6:H49, and O5:NM. Irrespective of serotype, 98% of the ovine STEC isolates possessed various combinations of the virulence-associated genes for Shiga toxin(s) and the attaching-and-effacing lesion (stx1, stx2, and eae), suggesting their potential for human pathogenicity. The most common toxin-eae genotype was positive for stx1, stx2, and eae. A Vero cell cytotoxicity assay demonstrated that 90% of the representative STEC isolates tested expressed the toxin gene. The report demonstrates that sheep transiently shed a variety of STEC strains, including E. coli O157:H7, that have potential as human pathogens
Sweep net sampling of spring and winter wheat (Triticum spp.) was conducted in 2007 and 2008 at the Fort Ellis Research and Extension Center, Montana State University, Bozeman, MT to determine ...hymenoptera parasitoid family composition, abundance, and diversity in two wheat-fallow cropping systems managed by either tillage, herbicides, or domestic sheep (Ovis aries) grazing. Eleven hymenopteran families classified as parasitoids were captured in 2007 and 16 families in 2008. The mean abundance of parasitoids was greatest (P ≤ 0.05) in crops where the fallow component of the rotation was managed with sheep grazing, as opposed to tillage and herbicide systems. Family diversity, as indexed by Simpson's D, did not differ between fallow management treatments (P = 0.88) or cropping system (P = 0.74) but did differ between study year (P ≤ 0.01).
The purpose of this study was to develop a sheep model to investigate reproduction, transmission, and shedding of Escherichia coli O157:H7 in ruminants. In addition, we investigated the effect of ...diet change on these parameters. Six groups of twin lambs given oral inoculations of 10(5) or 10(9) CFU of E. coli O157:H7 and their nondosed mothers were monitored for colonization by culture of fecal samples. A modified selective enrichment protocol that detected E. coli O157:H7 at levels as low as 0.06 CFU per g of ovine feces was developed. Horizontal transmission of infection occurred between the lambs and most of the nondosed mothers. When animals were kept in confinement and given alfalfa pellet feed, lambs receiving the higher dose shed the bacteria sooner and longer than all other animals. However, when the animals were released onto a sagebrush-bunchgrass range, every animal, regardless of its previous status (dosed at one of the inoculum levels tested or nondosed) shed E. coli O157:H7 uniformly. Shedding persisted for 15 days, after which all animals tested negative. E. coli O157:H7 reproduction and transmission and the combined effect of diet change and feed withholding were also investigated in a pilot study with experimentally inoculated rams. Withholding feed induced animals to shed the bacteria either by triggering growth of E. coli O157:H7 present in the intestines or by increasing susceptibility to infection. Introduction of a dietary change with brief starvation caused uniform shedding and clearance of E. coli O157:H7, and all animals then tested negative for the bacteria. This work suggests that appropriate preharvest management to control diet may significantly reduce the risk of E. coli O157:H7-positive animals going to slaughter
Late gestation supplementation of feed additives, such as rumen undegradable intake protein (RUIP), vitamin E, Zn, and chlortetracycline, has inconsistently improved ewe/lamb productivity. In 3 ...experiments, Western white-faced ewes were supplemented for at least 30 d during late gestation with 204 g/(ewe·d) on a DM basis of high (HS; 12.5% RUIP, 880 IU/kg of vitamin E, 176 mg/kg of Zn supplied by an AA complex, and 352 mg/kg of chlortetracycline) or low (LS; 7.56% RUIP and no supplemental vitamin E, Zn, or chlortetracycline) supplements. Ewes of different age (Exp. 1; 3- vs. 6-yr-old; n = 52) and BCS (Exp. 2; good vs. poor BCS; 3.0 and 1.7 ± 0.5, respectively; n = 40) were supplemented individually in a 2 x 2 factorial arrangement of treatments for 29 d. Thereafter, each ewe was group fed the appropriate supplement until lambing (14 ± 7 d). Ewe intake, colostral IgG, ewe and lamb parainfluenza type 3 (PI₃) titers, milk production, ewe BW and BCS change, and lamb production were measured in both experiments. In Exp. 3, approximately 600 ewes were group fed HS or LS over 2 yr. Ewe BW, ewe BCS, lamb production, and lamb survival was measured in Exp. 3 with groups within year as the experimental unit. In Exp. 1, lambs born to 3-yr-old ewes fed the HS had greater (P = 0.01) anti-PI₃ antibody titers than lambs born to 3-yr-old ewes fed the LS. Three-year-old ewes had greater (P < 0.01) DMI than 6-yr-old ewes. In Exp. 1 and 2, d 3 and 10 milk production differences (P less-than or equal to 0.10) were detected among treatments; however, lamb production did not differ among treatments in either experiment. In Exp. 3, late gestation supplementation did not affect indices of ewe or lamb production. Under the condition of these 3 studies, late gestation supplementation of HS or LS did not affect ewe productivity. Similarly, ewe age and BCS did not affect productivity, nor did ewe age or BCS interact with type of late gestation supplement.
PDF
