Crash-testing policies; How scenarios can support climate change policy formulation A methodological guide with case studies from Latin America

The objective of this handbook is to guide policy makers and practitioners from the public, private and research sector in the development and use of scenarios to support the inclusive formulation of policies and other decision-making processes related to complex issues taking place in changing environments. The lessons shared are based on nine policy formulation processes for climate in Latin America supported by the CCAFS future scenarios project since 2013. Five of these cases are discussed to exemplify the steps described to use scenarios and support the development of policies

Predictors of activity level and retention among African American lay health advisors (LHAs) from The National Witness Project: ...

Background Lay health advisor (LHA) programs are increasingly being implemented in the USA and globally in the context of health promotion and disease prevention. LHAs are effective in addressing health disparities when used to reach medically underserved populations, with strong evidence among African American and Hispanic women. Despite their success and the evidence supporting implementation of LHA programs in community settings, there are tremendous barriers to sustaining LHA programs and little is understood about their implementation and sustainability in “real-world” settings. The purpose of this study was to (1) propose a conceptual framework to investigate factors at individual, social, and organizational levels that impact LHA activity and retention; and (2) use prospective data to investigate the individual, social, and organizational factors that predict activity level and retention among a community-based sample of African American LHAs participating in an effective, evidence-based LHA program (National Witness Project; NWP). Methods Seventy-six LHAs were recruited from eight NWP sites across the USA. Baseline predictor data was collected from LHAs during a telephone questionnaire administered between 2010 and 2011. Outcome data on LHA participation and program activity levels were collected in the fall of 2012 from NWP program directors. Chi-square and ANOVA tests were used to identify differences between retained and completely inactive LHAs, and LHAs with high/moderate vs. low/no activity levels. Multivariable logistic regression models were conducted to identify variables that predicted LHA retention and activity levels. Results In multivariable models, LHAs based at sites with academic partnerships had increased odds of retention and high/moderate activity levels, even after adjusting for baseline LHA activity level. Higher religiosity among LHAs was associated with decreased odds of being highly/moderately active. LHA role clarity and self-efficacy were associated with retention and high/moderate activity in multivariable models unadjusted for baseline LHA activity level. Conclusions Organizational and role-related factors are critical in influencing the retention and activity levels of LHAs. Developing and fostering partnerships with academic institutions will be important strategies to promote successful implementation and sustainability of LHA programs. Clarifying role expectations and building self-efficacy during LHA recruitment and training should be further explored to promote LHA retention and participation

Maternal self-efficacy and 1–5-year-old children's brushing habits

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73681/1/j.1600-0528.2007.00313.x.pd

Deficient Plakophilin-1 Expression Due to a Mutation in PKP1 Causes Ectodermal Dysplasia-Skin Fragility Syndrome in Chesapeake Bay Retriever Dogs

In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis) are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children

Kidney disease in nail–patella syndrome

Nail–patella syndrome (NPS) is a pleiotropic autosomal-dominant disorder due to mutations in the gene LMX1B. It has traditionally been characterized by a tetrad of dermatologic and musculoskeletal abnormalities. However, one of the most serious manifestations of NPS is kidney disease, which may be present in up to 40% of affected individuals. Although LMX1B is a developmental LIM-homeodomain transcription factor, it is expressed in post-natal life in the glomerular podocyte, suggesting a regulatory role in that cell. Kidney disease in NPS seems to occur more often in some families with NPS, but it does not segregate with any particular mutation type or location. Two patterns of NPS nephropathy may be distinguished. Most affected individuals manifest only an accelerated age-related loss of filtration function in comparison with unaffected individuals. Development of symptomatic kidney failure is rare in this group, and proteinuria (present in approximately one-third) does not appear to be progressive. A small minority (5–10%) of individuals with NPS develop nephrotic-range proteinuria as early as childhood or young adulthood and progress to end-stage kidney failure over variable periods of time. It is proposed that this latter group reflects the effects of more global podocyte dysfunction, possibly due to the combination of a mutation in LMX1B along with an otherwise innocuous polymorphism or mutation involving any of several genes expressed in podocytes (e.g. NPHS2, CD2AP), the transription of which is regulated by LMX1B

Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease

Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases

Psychosocial factors and early childhood caries among low-income African–American children in Detroit

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75540/1/j.1600-0528.2006.00352.x.pd

Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion

Background: During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Intracellular thiols are maintained in their reduced state by a network of redox regulating peptides, proteins and enzymes such as glutathione, thioredoxins and thioredoxin reductase. Here we have investigated whether any relationship exists between age and secreted or cell surface thioredoxin-1, intracellular glutathione concentration and T cell surface thioredoxin 1 (Trx-1) and how this is related to interleukin (IL)-2 production.Results: Healthy older adults have reduced lymphocyte surface expression and lower circulating plasma Trx-1 concentrations. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show that cell surface Trx-1 is lowered, secretion of Trx-1 is decreased and the response to the lectin phytohaemagglutinin measured as IL-2 production is also affected. These effects are recapitulated by another glutathione depleting agent, diethylmaleate.Conclusion: Together these data suggest that a relationship exists between the intracellular redox compartment and Trx-1 proteins. Loss of lymphocyte surface Trx-1 may be a useful biomarker of healthy ageing. © 2013 Carilho Torrao et al.; licensee Chemistry Central Ltd

The International HapMap Project

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62838/1/nature02168.pd