Life Review In Aging: A Primer

Humans are narrative beings. We understand and speak of ourselves and the events of our lives in the context of stories. The stories we tell are influenced by our lived experiences, the quality of our memories (what’s recalled and forgotten), relationships, personality styles, values, accomplishments, regrets, spiritual beliefs, and a host of other factors. Telling our stories from the vantage point of old age is reflective of a maturational process of introspection and discovery called life review

Legacy Beliefs Across Generations: Learning From A Mixed Methods Approach

Dr. Tom Meuser gives an overview presentation of his research focused on legacy beliefs in advancing age.https://dune.une.edu/ssw_facpres/1000/thumbnail.jp

Comprehensive Geriatric Assessment: A Primer

Comprehensive Geriatric Assessment is an integrative approach to diagnosis, treatment and management of older adults that takes the whole person into account. While deficits may be a primary focus, strengths are also considered

Ion-Optical Design of a Pilot Separator for the JHP-ISOL

開始ページ、終了ページ: 冊子体のページ付

Drug screening using shape-based virtual screening and in vitro experimental models of cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is one of the most disregarded tropical neglected disease with the occurrence of self-limiting ulcers and triggering mucosal damage and stigmatizing scars, leading to huge public health problems and social negative impacts. Pentavalent antimonials are the first-line drug for CL treatment for over 70 years and present several drawbacks in terms of safety and efficacy. Thus, there is an urgent need to search for non-invasive, non-toxic and potent drug candidates for CL. In this sense, we have implemented a shape-based virtual screening approach and identified a set of 32 hit compounds. In vitro phenotypic screenings were conducted using these hit compounds to check their potential leishmanicidal effect towards Leishmania amazonensis (L. amazonensis). Two (Cp1 and Cp2) out of the 32 compounds revealed promising antiparasitic activities, exhibiting considerable potency against intracellular amastigotes present in peritoneal macrophages (IC₅₀ values of 9.35 and 7.25 μm, respectively). Also, a sterile cidality profile was reached at 20 μm after 48 h of incubation, besides a reasonable selectivity (≈8), quite similarly to pentamidine, a diamidine still in use clinically for leishmaniasis. Cp1 with an oxazolo[4,5-b]pyridine scaffold and Cp2 with benzimidazole scaffold could be developed by lead optimization studies to enhance their leishmanicidal potency

Belonging and participation as portrayed in the curriculum guidelines of five European countries

This study seeks to explore how the belonging and participation, as well as its related concepts, are framed in the national curriculum guidelines of the Netherlands, Finland, Iceland, Norway, and Sweden. We employed a scoping study with concept-mapping methodology. The results reveal macro level principles related to human rights and values, multiliteracy and language, policy measures and ideologies. Meso level principles stressed that education is supposed to guarantee a child’s overall development and skills acquisition, participation involvement in the activities related to a child’s environment and cultural heritage. The micro level principles were indicative of the need for inclusive and accessible physical and social environments, along with teaching methods which foster positive attitudes about diversity and teachers’ expertise levels to address diversity. We also found the importance of designing opportunities that encourage socializing, building relationships, and belongingness. Additionally, the results show how frequently the chosen key concepts are represented in the guidelines. Based on our study we can conclude that curriculum guidelines do not provide sufficent frameworks for promoting children’s belonging and participation. Further exploration on those concepts is needed, along with increased scholarly attention within the spheres of ECEC and compulsory education practice to enable inclusion for all children.publishedVersio

Ion-Optical Design of the High-Resolution Mass Separator for the Japanese Hadron Project (IV)

開始ページ、終了ページ: 冊子体のページ付

4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.

BackgroundChagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice.Methodology/principal findingsBoth acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart.Conclusions/significanceThe positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life