Regulatory T Cells in Asthma

Asthma is characterized by T helper cell 2 (Th2) type inflammation, leading to airway hyperresponsiveness and tissue remodeling. Th2 cell-driven inflammation is likely to represent an abnormal response to harmless airborne particles. These reactions are normally suppressed by regulatory T cells, which maintain airway tolerance. The anti-inflammatory cytokine IL-10 is likely to play a central role. The role of the cytokine transforming growth factor β (TGF-β) is more complex, with evidence for immune suppression and remodeling in the airways. In asthmatic individuals there is a breakdown in these regulatory mechanisms. There is emerging evidence that early life events, including exposure to allergen and infections, are critical in programming effective regulatory pathways to maintain pulmonary homeostasis. In this review we examine the clinical and experimental evidence for T regulatory cell function in the lung and discuss the events that might influence the functioning of these cells. Ultimately, the ability to enhance regulatory function in affected individuals may represent an effective treatment for asthma

A Two Hour Quasi-Period in an Ultra-luminous X-Ray source in NGC628

Quasi-periodic oscillations and X-ray spectroscopy are powerful probes of black hole masses and accretion disks, and here we apply these diagnostics to an ultraluminous X-ray source (ULX) in the spiral galaxy NGC628 (M74). This object was observed four times over two years with the Chandra X-ray Observatory and XMM-Newton, with three long observations showing dramatic variability, distinguished by a series of outbursts with a quasi-period (QPO) of 4,000-7,000 seconds. This is unique behavior among both ULXs and Galactic X-ray binaries due to the combination of its burst-like peaks and deep troughs, its long quasi-periods, its high variation amplitudes of $>90$%, and its substantial variability between observations. The X-ray spectra is fitted by an absorbed accretion disk plus a power-law component, suggesting the ULX was in a spectral state analogous to the Low Hard state or the Very High state of Galactic black hole X-ray binaries. A black hole mass of $\sim2$--$20\times10^3 M_\odot$ is estimated from the $f_b$--$M_\bullet$ scaling relation found in the Galactic X-ray binaries and active galactic nuclei.Comment: 12 pages, 3 figures. accepted for publication in ApJ Lette

Directory of Surveys in Developing Countries: Data on Families and Households, 1975–92

This directory of surveys contains data on families and households in developing countries. The emphasis is on intergenerational linkages as well as conjugal ties and co-residential arrangements. Surveys that do not situate individuals within a family or household context are excluded. Thus, many labor force surveys with data on the employment status and earnings of men and women are not included unless they also collected data on respondents’ children and/or households. The same is true of contraceptive prevalence surveys that limit their attention to women’s reproductive behavior. The majority of surveys included in the directory are either household-based or woman-based. Most of the information for this directory was collected through two mailings to a total of 1,250 individuals or institutions in developing and developed countries. Requests for information were also mailed directly to various institutions involved in data collection and storage. Recipients were informed about the project’s goals and asked to complete a questionnaire on each survey for which they were responsible or of which they had specific knowledge

Are we asking the right questions? Working with the LGBTQ+ community to prioritise healthcare research themes.

BackgroundConversations about research priorities with members of the public are rarely designed specifically to include people who identify as Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ+) and are not researchers.MethodsGenerally, to address this gap, and specifically, to inform future research for CLS, we carried out a rapid review of published research priority sets covering LGBTQ+ topics, and an online workshop to prioritise identified themes.ResultsRapid review: results. The rapid review identified 18 LGBTQ+ research priority sets. Some focussed on specific populations such as women or men, younger or older people or people living within families. Five addressed transgender and gender non- conforming populations. All of the research priority sets originated from English-speaking, high and middle-income countries (UK, US, Canada, and Australia), and date from 2016 onwards. Prioritization approaches were wide-ranging from personal commentary to expert workshops and surveys. Participants involved in setting priorities mostly included research academics, health practitioners and advocacy organisations, two studies involved LGBTQ+ public in their process. Research priorities identified in this review were then grouped into themes which were prioritised during the workshop. Workshop: results. For the workshop, participants were recruited using local (Cambridge, UK) LGBTQ+ networks and a national advert to a public involvement in research matching website to take part in an online discussion workshop. Those that took part were offered payment for their time in preparing for the workshop and taking part. Participants personal priorities and experiences contributed to a consensus development process and a final ranked list of seven research themes and participants' experiences of healthcare, mental health advocacy, care homes, caring responsibilities, schools and family units added additional context.ConclusionsFrom the workshop the three research themes prioritised were: healthcare services delivery, prevention, and particular challenges / intersectionality of multiple challenges for people identifying as LGBTQ+. Research themes interconnected in many ways and this was demonstrated by the comments from workshop participants. This paper offers insights into why these priorities were important from participants' perspectives and detail about how to run an inclusive and respectful public involvement research exercise. On a practical level these themes will directly inform future research direction for CLS

Accumulation of metabolic cardiovascular risk factors in black and white young adults over 20 years

BACKGROUND: Cross-sectional clustering of metabolic risk factors for cardiovascular disease in middle-aged adults is well described, but less is known regarding the order in which risk factors develop through young adulthood and their relation to subclinical atherosclerosis. METHOD AND RESULTS: A total of 3178 black and white women and men in the Coronary Artery Risk Development in Young Adults study were assessed to identify the order in which cardiovascular disease risk factors including diabetes, hypertension, dyslipidemia (low high-density lipoprotein cholesterol or high triglyceride levels), hypercholesterolemia (high total or low-density lipoprotein cholesterol), and obesity develop. Observed patterns of risk factor development were compared with those expected if risk factors accumulated randomly, given their overall distribution in the population. Over the 20 years of follow-up, 80% of participants developed at least 1 risk factor. The first factor to occur was dyslipidemia in 39% of participants, obesity in 20%, hypercholesterolemia in 11%, hypertension in 7%, and diabetes in 1%. Dyslipidemia was the only risk factor both to occur first and to be followed by additional risk factors more often than expected (P \u3c 0.001 for both). Order of risk factor accrual did not affect subclinical atherosclerosis at year 20. Results were similar by sex, race, and smoking status. CONCLUSIONS: Multiple patterns of cardiovascular risk factor development were observed from young adulthood to middle age. Dyslipidemia, a potentially modifiable condition, often preceded the development of other risk factors and may be a useful target for intervention and monitoring

Viral factors in influenza pandemic risk assessment

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk

Association of the degree of adiposity and duration of obesity with measures of cardiac structure and function: The CARDIA study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109634/1/oby20865.pd

Proteomic Analysis of Saliva from Patients with Oral Chronic Graft-Versus-Host Disease

AbstractChronic graft-versus-host disease (cGVHD) is an immune-mediated disorder and is the major long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The oral mucosa, including the salivary glands, is affected in the majority of patients with cGVHD; however, at present there is only a limited understanding of disease pathobiology. In this study, we performed a quantitative proteomic analysis of saliva pooled from patients with and without oral cGVHD—cGVHD(+) and cGVHD(−), respectively—using isobaric tags for relative and absolute quantification labeling, followed by tandem mass spectrometry. Among 249 salivary proteins identified by tandem mass spectrometry, 82 exhibited altered expression in the oral cGVHD(+) group compared with the cGVHD(−) group. Many of the identified proteins function in innate or acquired immunity, or are associated with tissue maintenance functions, such as proteolysis or the cytoskeleton. Using ELISA immunoassays, we further confirmed that 2 of these proteins, IL-1 receptor antagonist and cystatin B, showed decreased expression in patients with active oral cGVHD (P < .003). Receiver operating curve characteristic analysis revealed that these 2 markers were able to distinguish oral cGVHD with a sensitivity of 85% and specificity of 60%, and showed slightly better discrimination in newly diagnosed patients evaluated within 12 months of allo-HSCT (sensitivity, 92%; specificity 73%). In addition to identifying novel potential salivary cGVHD biomarkers, our study demonstrates that there is coordinated regulation of protein families involved in inflammation, antimicrobial defense, and tissue protection in oral cGVHD that also may reflect changes in salivary gland function and damage to the oral mucosa