The Benefits and Challenges of Preconsent in a Multisite, Pediatric Sickle Cell Intervention Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133619/1/pbc26013.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133619/2/pbc26013_am.pd

Compromised NLRP3 and AIM2 inflammasome function in autoimmune NZB/W F1 mouse macrophages

Inflammasomes are protein complexes activated by infection and cellular stress that promote caspase-1 activation and subsequent inflammatory cytokine processing and cell death. It has been anticipated that inflammasome activity contributes to autoimmunity. However, we previously showed that macrophages from autoimmune New Zealand Black (NZB) mice lack NLRP3 inflammasome function, and their AIM2 inflammasome responses are compromised by high expression of the AIM2 antagonist protein p202. Here we found that the point mutation leading to lack of NLRP3 expression occurred early in the NZB strain establishment, as it is shared with the related obese strain NZO, but not with the unrelated New Zealand White (NZW) strain. The first cross progeny of NZB and NZW mice develop more severe lupus nephritis than the NZB strain. We have compared AIM2 and NLRP3 inflammasome function in macrophages from NZB, NZW and NZB/W F1 mice. The NZW parental strain showed strong inflammasome function, whilst the NZB/W F1 have haploinsufficient expression of NLRP3 and show reduced NLRP3 and AIM2 inflammasome responses, particularly at low stimulus strength. It remains to be established whether the low inflammasome function could contribute to loss of tolerance and the onset of autoimmunity in NZB and NZB/W F1. However, with amplifying inflammatory stimuli through the course of disease, the NLRP3 response in the NZB/W F1 may be sufficient to contribute to kidney damage at later stages of disease. This article is protected by copyright. All rights reserved

Pregnancy-associated serum N-glycome changes studied by high-throughput MALDI-TOF-MS

Pregnancy requires partial suppression of the immune system to ensure maternal-foetal tolerance. Protein glycosylation, and especially terminal sialic acid linkages, are of prime importance in regulating the pro- and anti-inflammatory immune responses. However, little is known about pregnancy-associated changes of the serum N-glycome and sialic acid linkages. Using a combination of recently developed methods, i.e. derivatisation that allows the distinction between α2,3- and α2,6-linked sialic acids by high-throughput MALDI-TOF-MS and software-assisted data processing, we analysed the serum N-glycome of a cohort of 29 healthy women at 6 time points during and after pregnancy. A total of 77 N-glycans were followed over time, confirming in part previous findings while also revealing novel associations (e.g. an increase of FA2BG1S1(6), FA2G1S1(6) and A2BG2S2(6) with delivery). From the individual glycans we calculated 42 derived traits. With these, an increase during pregnancy and decrease after delivery was observed for both α2,3- and α2,6-linked sialylation. Additionally, a difference in the recovery speed after delivery was observed for α2,3- and α2,6-linked sialylation of triantennary glycans. In conclusion, our new high-throughput workflow allowed the identification of novel plasma glycosylation changes with pregnancy

Examining differential responses to the Take Care of Me trial: A latent class and moderation analysis

Given prevalent alcohol misuse-emotional comorbidities among young adults, we developed an internet-based integrated treatment called Take Care of Me. Although the treatment had an impact on several secondary outcomes, effects were not observed for the primary outcome. Therefore, the goal of the current study was to examine heterogeneity in treatment responses. The initial RCT randomized participants to either a treatment or psychoeducational control condition. We conducted an exploratory latent class analysis to distinguish individuals based on pre-treatment risk and then used moderated regressions to examine differential treatment responses based on class membership. We found evidence for three distinct groups. Most participants fell in the “low severity” group (n = 123), followed by the “moderate severity” group (n = 57) who had a higher likelihood of endorsing a previous mental health diagnosis and treatment and higher symptom severity than the low group. The “high severity” group (n = 42) endorsed a family history of alcoholism, and the highest symptom severity and executive dysfunction. Moderated regressions revealed significant class differences in treatment responses. In the treatment condition, high severity (relative to low) participants reported higher alcohol consumption and hazardous drinking and lower quality of life at follow-up, whereas moderate severity (relative to low) individuals had lower alcohol consumption at follow-up, and lower hazardous drinking at end-of-treatment. No class differences were found for participants in the control group. Higher risk individuals in the treatment condition had poorer responses to the program. Tailoring interventions to severity may be important to examine in future research

Hepatitis C Virus Transmission Clusters in Public Health and Correctional Settings, Wisconsin, USA, 2016-20171.

Ending the hepatitis C virus (HCV) epidemic requires stopping transmission among networks of persons who inject drugs. Identifying transmission networks by using genomic epidemiology may inform community responses that can quickly interrupt transmission. We retrospectively identified HCV RNA-positive specimens corresponding to 459 persons in settings that use the state laboratory, including correctional facilities and syringe services programs, in Wisconsin, USA, during 2016-2017. We conducted next-generation sequencing of HCV and analyzed it for phylogenetic linkage by using the Centers for Disease Control and Prevention Global Hepatitis Outbreak Surveillance Technology platform. Analysis showed that 126 persons were linked across 42 clusters. Phylogenetic clustering was higher in rural communities and associated with female sex and younger age among rural residents. These data highlight that HCV transmission could be reduced by expanding molecular-based surveillance strategies to rural communities affected by the opioid crisis

Assessment of Road Culverts as Passage Barriers to Wild and Stocked Trout in Pennsylvania Headwaters

One of the primary threats to brook trout in Pennsylvania is population fragmentation due to habitat alteration. Road culverts in particular can isolate populations by reducing access to upstream spawning habitat. To categorize the degree to which culverts prevent fish movement, watershed managers use physical measurements to classify the passability of the each culvert. The North Atlantic Aquatic Connectivity Collaborative (NAACC) conservatively categorizes culverts as “no AOP (Aquatic Organism Passage)” or “red culverts” when they are considered a barrier to aquatic organisms. The Little Bear Creek watershed, a wild trout stream in the Loyalsock watershed, contains three culverts categorized as “reduced AOP” or “gray culverts” that require further investigation to determine actual organism passage. It is unknown whether these gray culverts are indeed barriers to migratory fish, especially native trout. To measure how passable these culverts are, we tagged 546 wild trout in 2015 and 2016 with passive integrated transponder (PIT) tags, distributed up and downstream of each culvert site and a control site without a culvert. Results show that trout are differences in movements between culvert types, implicating a barrier issue in Little Bear’s tributaries. The only metal corrugated culvert in the watershed, which lies on the upper most extent of Sand Spring Run, has proven to be the most passable of the culverts with an average of 0.85 movements per day. A small box culvert on the lower extent of Sand Spring Run had an average of 0.1 movements per day. The largest culvert, a more recently built box culvert close to the mouth of Red Run, had an average of 0.01 movements per day. None of the movements in Red Run were upstream movements. The barrier-free site on Painter Run resulted in an average of 0.27 movements per day. We will further test for correlations of trout movements with daily stream conditions such as temperature and water level. By “ground-truthing” culvert assessment methods, we anticipate our study will ultimately help watershed managers better prioritize culverts for removal or replacement

Birth Control Use and Access Including Pharmacist-Prescribed Contraception Services during COVID-19

The COVID-19 pandemic influenced health care with effects on contraception access emerging. The study objectives were to analyze pandemic impacts on birth control (BC) use and access; and evaluate perceptions of pharmacist-prescribed BC. A 50-item survey was distributed by 31 Michigan community pharmacies to women aged 18–45 over a three-month period. The survey link was also posted on two websites. 147 surveys were analyzed. Respondents were 29 ± 7.9 years old, primarily white (77%) and straight (81%). Fifty-eight percent of respondents used prescription BC, mostly to prevent pregnancy (84%) with oral pills (76%) being the most common formulation. Some BC users (25%) were worried about BC access and 27% had difficulty taking BC regularly. Half of the respondents (50%) would likely use pharmacist-prescribed BC if available, with advantages being more convenient than visiting a doctor’s office (71%) and easier access (69%). The major concern about pharmacist-prescribed BC was women not receiving PAP smears and screenings (61%). Respondents reported high confidence (72%) in pharmacist-prescribed BC and believe it would help prevent unintended pregnancies (69%). Some respondents experienced altered BC use and access. Half of the respondents supported pharmacist-prescribed BC. Pharmacist-prescribed BC could help solve pandemic-related access problems

Belonging in Education: Lessons from the Belonging Project

This paper presents some preliminary findings from The Belonging Project&mdash;a longitudinal learning and teaching research project seeking to develop and define a new approach to student engagement. In this project, the concept of belonging is used as a tactic to engage both staff and students in the School of Media and Communication at RMIT University as part of the project&rsquo;s aim to improve the student experience. This paper maps the way in which we use belonging&mdash;defined in relation to the educational experience&mdash;as a point of departure to achieve this outcome. Having established our definition of belonging and its purpose in our project, we then discuss some key results of focus groups with students, outlining the way in which students navigate issues of transition, interdisciplinarity, and notions of space and place, in their relationship to university and campus life.&nbsp;</em