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Giardiasis and other protozoan infections are major worldwide causes of morbidity and mortality, yet development of new antimicrobial agents with improved efficacy and ability to override increasingly common drug resistance remains a major challenge. Antimicrobial drug development typically proceeds by broad functional screens of large chemical libraries or hypothesis-driven exploration of single microbial targets, but both strategies have challenges that have limited the introduction of new antimicrobials. Here, we describe an alternative drug development strategy that identifies a sufficient but manageable number of promising targets, while reducing the risk of pursuing targets of unproven value. The strategy is based on defining and exploiting the incompletely understood adduction targets of 5-nitroimidazoles, which are proven antimicrobials against a wide range of anaerobic protozoan and bacterial pathogens. Comprehensive adductome analysis by modified click chemistry and multi-dimensional proteomics were applied to the model pathogen Giardia lamblia to identify dozens of adducted protein targets common to both 5'-nitroimidazole-sensitive and -resistant cells. The list was highly enriched for known targets in G. lamblia, including arginine deiminase, α-tubulin, carbamate kinase, and heat shock protein 90, demonstrating the utility of the approach. Importantly, over twenty potential novel drug targets were identified. Inhibitors of two representative new targets, NADP-specific glutamate dehydrogenase and peroxiredoxin, were found to have significant antigiardial activity. Furthermore, all the identified targets remained available in resistant cells, since giardicidal activity of the respective inhibitors was not impacted by resistance to 5'-nitroimidazoles. These results demonstrate that the combined use of click chemistry and proteomics has the potential to reveal alternative drug targets for overcoming antimicrobial drug resistance in protozoan parasites.

To provide culturally-centered care to clients and develop interventions that meet the client's holistic needs, occupational therapists need to consider social and physical environments affecting participation in culturally meaningful occupations. Using a case study, this paper describes the use of the concept of social and environmental determinants of occupation (SEDO) as a necessary strategy to incorporate in clinical practice to determine how SEDO intersect, resulting in occupational justices/injustices that influence access to participation. SEDO are defined as broad (and intersecting) social and environmental factors that increase or limit an individual, community, or population's ability to participate in culturally meaningful occupations of their choice. This information can then be used to develop strategies that more holistically address the SEDO experienced by our clients. The SEDO process refocuses research and practice with more inclusive attention to how these intersecting factors influence the client's ability to access culturally meaningful occupations, provide opportunities for advocacy and empowerment, and better address the needs of our clients. The SEDO strategy can provide data for development of more holistic client-centered interventions. [ABSTRACT FROM AUTHOR]

The Sanak-Baranof belt includes a series of near-trench plutons that intrude the outboard Chugach-Prince William terrane over ~2200 km along the southern Alaskan margin. We present new petrological, geochronological, and geochemical data for comagmatic microgranitoid enclaves and granitoid rocks from the Crawfish Inlet (ca. 53-47 Ma) and Krestof Island (ca. 52 Ma) plutons on Baranof and Krestof Islands, as well as the Mount Stamy (ca. 51 Ma) and Mount Draper (ca. 54-53 Ma) plutons and associated mafic rocks that intrude the Boundary block at Nunatak Fiord near Yakutat, Alaska, USA. These data suggest that intrusion of the Sanak-Baranof belt plutons is actually a tale of two distinct belts: a western belt with crystallization ages that young systematically from west to east (63-56 Ma) and an eastern belt with crystallization ages ranging from 55 to 47 Ma, but with no clear age progression along the margin. Hf isotope analyses of magmatic zircon from the western Sanak-Baranof belt become increasingly evolved toward the east with εHft = 9.3 ± 0.7 on Sanak Island versus εHft = 5.1 ± 0.5 for the Hive Island pluton in Resurrection Bay. The Hf isotope ratios of eastern Sanak-Baranof belt rocks also vary systematically with age but in reverse, with more evolved ratios in the oldest plutons (εHft = +4.7 ± 0.7) and more primitive ratios in the youngest plutons (εHft = +13.7 ± 0.7). We propose that these findings indicate distinct modes of origin and emplacement histories for the western and eastern segments of the Sanak-Baranof belt, and that the petrogenesis of eastern Sanak-Baranof belt plutons (emplaced subsequent to 57-55 Ma) was associated with an increasing mantle component supplied to the youngest eastern Sanak-Baranof belt magmas. These plutons reveal important information about offshore plate geometries and a dynamic period of plate reorganization ca. 57-55 Ma, but a clearer picture of the tectonic setting that facilitated these Sanak-Baranof belt intrusions cannot be resolved until the magnitude and significance of lateral translation of the Chugach-Prince William terrane are better understood. [ABSTRACT FROM AUTHOR]

Direct experience is a powerful learning and teaching tool. However, when trying to teach students about natural hazards such as earthquakes, direct experience is not the best idea. Depending on location, it might be difficult to help young students understand the impact of natural hazards on their lives. Students will naturally find it challenging to understand something they have never experienced. Technology such as mobile devices, smart boards, laptops, tablets and other types of devices can offer students safe glimpses at the effects of natural hazards on human life and property. The technology enables students to gain experiences with natural hazards without actually having to live through the experience. In this article, the authors present the exploration of earthquakes and other natural hazards using technology. While the authors recognize that not all classrooms will have one-to-one access, these activities presented in this article can also be done as centers with a smaller number of devices needed.

Identifies key characteristics of indigenous sole-parent families relative to other such Australian families and analyzes the factors associated with their ongoing levels of economic disadvantage. Raises issues about the efficacy of job-skill-development programs. (Author/JOW)

Individuals with disabilities tend to have more health care access problems, have secondary health conditions, have unmet health care needs, and are less likely to be satisfied with medical care [...], This study examined the relationship between disability, gender and access to physician services due to cost using data from the 2005 Behavioral Risk Factor Surveillance System. Results showed that women with disabilities are less likely than women without disabilities and men with disabilities to report not having seen a physician due to cost. A person with a disability is twice as likely to report not having seen a physician due to cost and women are approximately one and one half times as likely to report not having seen a physician due to cost. Implications for rehabilitation professionals focus on socioeconomic factors such as education, employment and training to increase income and improve access to health plans that provide access to physician services.

Life satisfaction is an important concept as it has been widely considered to be a central aspect of human welfare (Haybron, 2005). It has been further defined as having a [...], The purpose of this paper was to determine the relationship between race, perceptions of racism and disability on life satisfaction. Data from the 2005 Behavioral Risk Factor Surveillance System (BRFSS) examined through chi square and regression analysis found that African Americans with disabilities and without disabilities show a stronger relationship between dissatisfaction with life and perceived racism in the work and health care settings than Caucasians. Other issues such as lower employment and income contribute to dissatisfaction with life significantly more for African Americans. Regression analysis showed that having a disability and perceived racism decreased the likelihood of life satisfaction. These results have implications for rehabilitation professionals who need to consider not only disability, but race when working with clients to achieve an increase in life satisfaction.