Ampicillin-Improved Glucose Tolerance in Diet-Induced Obese C57BL/6NTac Mice Is Age Dependent

Ampicillin has been shown to improve glucose tolerance in mice. We hypothesized that this effect is present only if treatment is initiated prior to weaning and that it disappears when treatment is terminated. High-fat fed C57BL/6NTac mice were divided into groups that received Ampicillin at different ages or not at all. We found that both diet and Ampicillin significantly changed the gut microbiota composition in the animals. Furthermore, there was a significant improvement in glucose tolerance in Ampicillin-treated, five-week-old mice compared to nontreated mice in the control group. At study termination, expressions of mRNA coding for tumor necrosis factor, serum amyloid A, and lactase were upregulated, while the expression of tumor necrosis factor (ligand) superfamily member 15 was downregulated in the ileum of Ampicillin-treated mice. Higher dendritic cell percentages were found systemically in high-fat diet mice, and a lower tolerogenic dendritic cell percentage was found both in relation to high-fat diet and late Ampicillin treatment. The results support our hypothesis that a “window” exists early in life in which an alteration of the gut microbiota affects glucose tolerance as well as development of gut immunity and that this window may disappear after weaning

Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. RESULTS: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. CONCLUSIONS: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world

A dual thromboxane inhibitor and thromboxane receptor antagonist prevents pig myocardial infarction induced by coronary thrombosis

peer reviewe

Epistemic Dependence and Collective Scientific Knowledge

I argue that scientific knowledge is collective knowledge, in a sense to be specified and defended. I first consider some existing proposals for construing collective knowledge and argue that they are unsatisfactory, at least for scientific knowledge as we encounter it in actual scientific practice. Then I introduce an alternative conception of collective knowledge, on which knowledge is collective if there is a strong form of mutual epistemic dependence among scientists, which makes it so that satisfaction of the justification condition on knowledge ineliminably requires a collective. Next, I show how features of contemporary science support the conclusion that scientific knowledge is collective knowledge in this sense. Finally, I consider implications of my proposal and defend it against objections. © 2013 Springer Science+Business Media Dordrecht

Type six secretion system of Bordetella bronchiseptica and adaptive immune components limit intracellular survival during infection

The Type Six Secretion System (T6SS) is required for Bordetella bronchiseptica cytotoxicity, cytokine modulation, infection, and persistence. However, one-third of recently sequenced Bordetella bronchiseptica strains of the predominantly human-associated Complex IV have lost their T6SS through gene deletion or degradation. Since most human B. bronchiseptica infections occur in immunocompromised patients, we determine here whether loss of Type Six Secretion is beneficial to B. bronchiseptica during infection of immunocompromised mice. Infection of mice lacking adaptive immunity (Rag1-/- mice) with a T6SS-deficient mutant results in a hypervirulent phenotype that is characterized by high numbers of intracellular bacteria in systemic organs. In contrast, wild-type B. bronchiseptica kill their eukaryotic cellular hosts via a T6SS-dependent mechanism that prevents survival in systemic organs. High numbers of intracellular bacteria recovered from immunodeficient mice but only low numbers from wild-type mice demonstrates that B. bronchiseptica survival in an intracellular niche is limited by B and T cell responses. Understanding the nature of intracellular survival during infection, and its effects on the generation and function of the host immune response, are important to contain and control the spread of Bordetella-caused disease.Liron Bendor, Laura S. Weyrich, Bodo Linz, Olivier Y. Rolin, Dawn L. Taylor, Laura L. Goodfield, William E. Smallridge, Mary J. Kennett, Eric T. Harvil

Scientific Perspectives, Feminist Standpoints, and Non-silly Relativism

Defences of perspectival realism are motivated, in part, by an attempt to find a middle ground between the realist intuition that science seems to tell us a true story about the world, and the Kuhnian intuition that scientific knowledge is historically and culturally situated. The first intuition pulls us towards a traditional, absolutist scientific picture, and the second towards a relativist one. Thus, perspectival realism can be seen as an attempt to secure situated knowledge without entailing epistemic relativism. A very similar motivation is behind feminist standpoint theory, a view which aims to capture the idea that knowledge is socially situated, whilst retaining some kind of absolutism. Elsewhere I argue that the feminist project fails to achieve this balance; its commitment to situated knowledge unavoidably entails epistemic relativism (though of an unproblematic kind), which allows them to achieve all of their feminist goals. In this paper I will explore whether the same arguments apply to perspectival realism. And so I will be asking whether perspectival realism too is committed to an unproblematic kind of relativism, capable of achieving scientific goals; or, whether it succeeds in carving out a third view, between or beyond the relativism/absolutism dichotomy