Predicting treatment efficacy via quantitative magnetic resonance imaging: a Bayesian joint model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90333/1/RSSC_1015_sm_SupportingInformation.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90333/2/j.1467-9876.2011.01015.x.pd

Association of Alleles Carried at TNFA -850 and BAT1 -22 with Alzheimer\u27s Disease

Background: Inflammatory changes are a prominent feature of brains affected by Alzheimer\u27s disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases. Methods: Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE ε4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases. Results: APOE ε4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE ε4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases. Conclusion: These findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology

Beyond literacy and numeracy in patient provider communication: Focus groups suggest roles for empowerment, provider attitude and language

<p>Abstract</p> <p>Background</p> <p>Although the number of people living in the United States with limited English proficiency (LEP) is substantial, the impact of language on patients' experience of provider-patient communication has been little explored.</p> <p>Methods</p> <p>We conducted a series of 12 exploratory focus groups in English, Spanish and Cantonese to elicit discussion about patient-provider communication, particularly with respect to the concerns of the health literacy framework, i.e. ability to accurately understand, interpret and apply information given by providers. Within each language, 2 groups had high education and 2 had low education participants to partially account for literacy levels, which cannot be assessed consistently across three languages. Eighty-five (85) adults enrolled in the focus groups. The resulting video tapes were transcribed, translated and analyzed via content analysis.</p> <p>Results</p> <p>We identified 5 themes: 1) language discordant communication; 2) language concordant communication; 3) empowerment; 4) providers' attitudes; 5) issues with the health care system. Despite efforts by facilitators to elicit responses related to cognitive understanding, issues of interpersonal process were more salient, and respondents did not readily separate issues of accurate understanding from their overall narratives of experience with health care and illness. Thematic codes often appeared to be associated with education level, language and/or culture.</p> <p>Conclusion</p> <p>Our most salient finding was that for most of our participants there was no clear demarcation between literacy and numeracy, language interpretation, health communication, interpersonal relations with their provider and the rest of their experience with the health care system.</p

Engaging patients, clinicians and health funders in weight management: the Counterweight Programme.

Background. The Counterweight Programme provides an evidence based and effective approach for weight management in routine primary care. Uptake of the programme has been variable for practices and patients. Aim. To explore key barriers and facilitators of practice and patient engagement in the Counterweight Programme and to describe key strategies used to address barriers in the wider implementation of this weight management programme in UK primary care. Methods. All seven weight management advisers participated in a focus group. In-depth interviews were conducted with purposeful samples of GPs (n = 7) and practice nurses (n = 15) from 11 practices out of the 65 participating in the programme. A total of 37 patients participated through a mixture of in-depth interviews (n = 18) and three focus groups. Interviews and focus groups were analysed for key themes that emerged. Results. Engagement of practice staff was influenced by clinicians beliefs and attitudes, factors relating to the way the programme was initiated and implemented, the programme content and organizational/contextual factors. Patient engagement was influenced by practice endorsement of the programme, clear understanding of programme goals, structured proactive follow-up and perception of positive outcomes. Conclusions. Having a clear understanding of programme goals and expectations, enhancing self-efficacy in weight management and providing proactive follow-up is important for engaging both practices and patients. The widespread integration of weight management programmes into routine primary care is likely to require supportive public policy

Marine pelagic ecosystems: the West Antarctic Peninsula

The marine ecosystem of the West Antarctic Peninsula (WAP) extends from the Bellingshausen Sea to the northern tip of the peninsula and from the mostly glaciated coast across the continental shelf to the shelf break in the west. The glacially sculpted coastline along the peninsula is highly convoluted and characterized by deep embayments that are often interconnected by channels that facilitate transport of heat and nutrients into the shelf domain. The ecosystem is divided into three subregions, the continental slope, shelf and coastal regions, each with unique ocean dynamics, water mass and biological distributions. The WAP shelf lies within the Antarctic Sea Ice Zone (SIZ) and like other SIZs, the WAP system is very productive, supporting large stocks of marine mammals, birds and the Antarctic krill, Euphausia superba. Ecosystem dynamics is dominated by the seasonal and interannual variation in sea ice extent and retreat. The Antarctic Peninsula is one among the most rapidly warming regions on Earth, having experienced a 28C increase in the annual mean temperature and a 68C rise in the mean winter temperature since 1950. Delivery of heat from the Antarctic Circumpolar Current has increased significantly in the past decade, sufficient to drive to a 0.68C warming of the upper 300 m of shelf water. In the past 50 years and continuing in the twenty-first century, the warm, moist maritime climate of the northern WAP has been migrating south, displacing the once dominant cold, dry continental Antarctic climate and causing multi-level responses in the marine ecosystem. Ecosystem responses to the regional warming include increased heat transport, decreased sea ice extent and duration, local declines in icedependent Ade´lie penguins, increase in ice-tolerant gentoo and chinstrap penguins, alterations in phytoplankton and zooplankton community composition and changes in krill recruitment, abundance and availability to predators. The climate/ecological gradients extending along theWAPand the presence of monitoring systems, field stations and long-term research programmes make the region an invaluable observatory of climate change and marine ecosystem response

PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects.

The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5'-splice site (5'SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5'SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches

Yersinia pestis targets neutrophils via complement receptor 3

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111208/1/cmi12391.pd

Atrazine-induced apoptosis of splenocytes in BALB/C mice

<p>Abstract</p> <p>Background</p> <p>Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR), is the most commonly applied broad-spectrum herbicide in the world. Unintentional overspray of ATR poses an immune function health hazard. The biomolecular mechanisms responsible for ATR-induced immunotoxicity, however, are little understood. This study presents on our investigation into the apoptosis of splenocytes in mice exposed to ATR as we explore possible immunotoxic mechanisms.</p> <p>Methods</p> <p>Oral doses of ATR were administered to BALB/C mice for 21 days. The histopathology, lymphocyte apoptosis and the expression of apoptosis-related proteins from the Fas/Fas ligand (FasL) apoptotic pathway were examined from spleen samples.</p> <p>Results</p> <p>Mice administered ATR exhibited a significant decrease in spleen and thymus weight. Electron microscope histology of ultrathin sections of spleen revealed degenerative micromorphology indicative of apoptosis of splenocytes. Flow cytometry revealed that the percentage of apoptotic lymphocytes increased in a dose-dependent manner after ATR treatment. Western blots identified increased expression of Fas, FasL and active caspase-3 proteins in the treatment groups.</p> <p>Conclusions</p> <p>ATR is capable of inducing splenocytic apoptosis mediated by the Fas/FasL pathway in mice, which could be the potential mechanism underlying the immunotoxicity of ATR.</p