Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats

Background Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Methods Female Sprague-Dawley rats (age 28 d) were randomly assigned (n = 10/group) to be fed a high fat 12% (wt) diet consisting of either corn oil (CO) or n-3 PUFA rich flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs) and thromoboxanes (TXBs) using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR). Results Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. Conclusions On the basis that the optimal n-3 PUFA sources should provide high digestibility and efficient tissue incorporation with the least tissue lipid peroxidation, TO and SO appeared to be the most beneficial of the n-3 PUFAs sources evaluated in this study

Consensus-based recommendations for investigating clinical heterogeneity in systematic reviews

Abstract Background Critics of systematic reviews have argued that these studies often fail to inform clinical decision making because their results are far too general, that the data are sparse, such that findings cannot be applied to individual patients or for other decision making. While there is some consensus on methods for investigating statistical and methodological heterogeneity, little attention has been paid to clinical aspects of heterogeneity. Clinical heterogeneity, true effect heterogeneity, can be defined as variability among studies in the participants, the types or timing of outcome measurements, and the intervention characteristics. The objective of this project was to develop recommendations for investigating clinical heterogeneity in systematic reviews. Methods We used a modified Delphi technique with three phases: (1) pre-meeting item generation; (2) face-to-face consensus meeting in the form of a modified Delphi process; and (3) post-meeting feedback. We identified and invited potential participants with expertise in systematic review methodology, systematic review reporting, or statistical aspects of meta-analyses, or those who published papers on clinical heterogeneity. Results Between April and June of 2011, we conducted phone calls with participants. In June 2011 we held the face-to-face focus group meeting in Ann Arbor, Michigan. First, we agreed upon a definition of clinical heterogeneity: Variations in the treatment effect that are due to differences in clinically related characteristics. Next, we discussed and generated recommendations in the following 12 categories related to investigating clinical heterogeneity: the systematic review team, planning investigations, rationale for choice of variables, types of clinical variables, the role of statistical heterogeneity, the use of plotting and visual aids, dealing with outlier studies, the number of investigations or variables, the role of the best evidence synthesis, types of statistical methods, the interpretation of findings, and reporting. Conclusions Clinical heterogeneity is common in systematic reviews. Our recommendations can help guide systematic reviewers in conducting valid and reliable investigations of clinical heterogeneity. Findings of these investigations may allow for increased applicability of findings of systematic reviews to the management of individual patients.http://deepblue.lib.umich.edu/bitstream/2027.42/112777/1/12874_2012_Article_987.pd

CD1a autoreactive T cells recognize natural skin oils that function as headless antigens

CD1a autoreactive T cells are common in human blood and skin, but the search for natural autoantigens has been confounded by background T cell responses to CD1 proteins and self lipids. After capturing CD1a-lipid complexes, we gently eluted ligands, while preserving unliganded CD1a for testing lipids from tissues. CD1a released hundreds of ligands of two types. Inhibitory ligands were ubiquitous membrane lipids with polar headgroups, whereas stimulatory compounds were apolar oils. CD1a autoantigens naturally accumulate in epidermis and sebum, where they were identified as squalene and skin waxes. T cell activation by skin oils suggests that headless mini-antigens nest within CD1a and displace non-antigenic resident lipids with large head groups. Oily autoantigens naturally coat the skin's surface, pointing to a new mechanism of barrier immunity

Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Distinct Airway Inflammatory Pathways Associated with Asthma Exacerbations are Modulated by Mepolizumab Therapy in Children

Rationale: Identification of specific airway inflammatory pathways can lead to effective personalized treatment with biologics in asthma and insights to mechanisms of action. Methods: 290 urban children with exacerbation-prone asthma and ≥150/mm3 blood eosinophils were randomized (1:1) to placebo or mepolizumab added to guideline-based care. Nasal lavage samples were collected at randomization and during treatment for RNA-sequencing, and analyzed by cell-deconvolution modular analysis to assess genome-wide expression patterns associated with exacerbation number and effect of treatment. Results: Mepolizumab significantly reduced the frequency of exacerbations compared to placebo. At randomization, there were no differences in expression between treatment groups; multiple modules were subsequently differentially expressed during mepolizumab but not placebo treatment. Furthermore, expression levels of multiple modules were associated with the exacerbation number during the study, with distinct relationships observed in the placebo and/or mepolizumab groups. Notably, higher expression at randomization of an eosinophil-associated module enriched for Type-2 genes including IL4, IL5, and IL13, was associated with increased exacerbations in placebo (β=0.19, p\u3c0.001), but not mepolizumab-treated children (interaction p\u3c0.01). Furthermore, mepolizumab treatment reduced expression of this module (Fold-change=0.62, p\u3c0.001). In contrast, higher expression at randomization of an eosinophil-associated module enriched for eosinophil activation (e.g. CD9) and mucus hypersecretion (e.g. MUC5AC) genes was associated with exacerbation number in both groups throughout the study (β=0.18, p\u3c0.01) and was unaltered by mepolizumab therapy. Conclusions: Multiple distinct airway inflammation patterns were identified associated with exacerbation frequency. These findings identify inflammatory endotypes and indicate likelihood and potential mechanisms of a beneficial clinical response to mepolizumab therapy to prevent exacerbations

An Initial Exploration of Engineering Student Perceptions of COVID’s Impact on Connectedness, Learning, and STEM Identity

This paper studied the development of STEM identity for freshman students in Engineering. An Urban Research University received a 5-year S-STEM award in fall 2018. So far, two cohorts of scholars have received the scholarship as well as academic support, mentoring support, and customized advising from faculty and upper level peers. The objective of this project is to help underrepresented and talented students in engineering to pursue an undergraduate degree. A Multi-Layered Mentoring(MLM) Program was established, and several interviews were conducted with scholarship recipients. The qualitative and qualitative analysis of the student success shows an improvement in GPA of students in the program as compared to the rest of the school. The students not only received financial help through the program based on their unmet needs, they are were placed in an engineering learning community (ELC). The participants in ELC and MLM programs agreed to participate in research studies to assess their success. This NSF funded program also helped freshman students be involved in a hands-on Design Innovations class where they learned design process and human centered design. The students were surveyed on a regular basis to identify their needs and were approached by faculty advisor as well as their mentors to trouble shoot their concerns and help them with both social and academic aspects of their concerns. The first cohort joined the program in AY 2019-2020, as freshmen. This cohort had experienced a full semester of in-person engagement before the COVID-19 hit in the middle of the second semester of their freshman year. We have researched the impact of the pandemic on their academic progress, sense of belonging, and STEM identity. The second cohort joined the program in AY 2020-2021. They have not had the chance to experience the campus life and their perspective of college life is very different than the first cohort. The STEM identity was one of the success indicators for freshman students who entered the university in one of the most difficult and un-usual circumstances under the COVID-19 pandemic