Alien Registration- Darkes, Thankful J. (Mapleton, Aroostook County)

https://digitalmaine.com/alien_docs/34069/thumbnail.jp

Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.

The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed

A league of their own: demographics, motivations and patterns of use of 1,955 male adult non-medical anabolic steroid users in the United States

Background: Rule violations among elite-level sports competitors and tragedies among adolescents have largely defined the issue of non-medical anabolic-androgenic steroid (NMAAS) use for the public and policy makers. However, the predominant and oft-ignored segment of the NMAAS community exists in the general population that is neither participating in competitive sports nor adolescent. A clearer profile of NMAAS users within the general population is an initial step in developing a full understanding of NMAAS use and devising appropriate policy and interventions. This survey sought to provide a more comprehensive profile of NMAAS users by accessing a large sample of user respondents from around the United States. Methods: U.S.-based male NMAAS users (n = 1955) were recruited from various Internet websites dedicated to resistance training activities and use of ergogenic substances, mass emails, and print media to participate in a 291-item web-based survey. The Internet was utilized to provide a large and geographically diverse sample with the greatest degree of anonymity to facilitate participation. Results: The majority of respondents did not initiate AAS use during adolescence and their NMAAS use was not motivated by athletics. The typical user was a Caucasian, highly-educated, gainfully employed professional approximately 30 years of age, who was earning an above-average income, was not active in organized sports, and whose use was motivated by increases in skeletal muscle mass, strength, and physical attractiveness. These findings question commonly held views of the typical NMAAS user and the associated underlying motivations. Conclusion: The focus on cheating athletes and at risk youth has led to ineffective policy as it relates to the predominant group of NMAAS users. Effective policy, prevention or intervention should address the target population(s) and their reasons for use while utilizing their desire for responsible use and education

Recognising the Significance of Early Years Practitioners as Creators of Knowledge

My inquiry revisits ideas of knowledge, exploring the essential components of a process which enables Early Years Practitioners to generate new knowledge about how to create and sustain rich learning for children through building their own learning and becoming knowledge creators within a learning community. Based on my participatory worldview, which acknowledges the interconnectedness of individuals and the importance of democratic ways of working, the thesis integrates first, second and third person strategies of inquiry. Engaging with others in a process of Collaborative Inquiry, practitioners were able to create and share their own theories of practice, becoming generators of change, making an experiential difference to children's well-being and learning. The research is grounded in the experience of practitioners, who have unique insights into the children and families with whom they work, and particular understandings about what is needed to meet the complexities of carrying out their roles effectively. This knowledge has traditionally not been listened to, and their voices have been silenced. By acknowledging their understanding in a collaborative context, practitioners were able to recognise the significance of their own inner knowing and began to value themselves, becoming confident to make changes to practice and build upon their learning. I reflect upon and discuss the main elements of a process by which practitioners might sustain themselves and advocate for the children in their care. I show how undertaking practitioner-led inquiry presents a way for practitioners to become more critically aware, learning with and from each other to deepen understanding of their pedagogy, and become more confident to articulate and develop practice. Locating our experiences within a wider social and political context, I offer a radical critique of notions of knowledge and neo-liberal influences on early childhood education, proposing an alternative perspective emerging from a democratic vision of participation and interconnectedness

CINESIOTERAPIA E TERAPIA COMPLEXA DESCONGESTIVA NO PÓS-OPERATÓRIO DE MASTECTOMIA RADICAL

Introdução: O câncer de mama é uma enfermidade amplamente estudada em vários aspectos, e seu diagnóstico provoca diversas mudanças no estado emocional das mulheres quando associado à mastectomia, um trauma de natureza física, psicológica, biológica e social (VALOIS, et al, 2019, p. 1). O câncer de mama é uma doença causada pela proliferação sem controle das células da glândula mamária, dando como resultado a formação de um tumor (INCA 2020). Em um estudo realizado por Alves (2019), na cirurgia de mastectomia radical é realizado a remoção das glândulas mamárias, dos músculos peitorais maior e menor e o esvaziamento axilar completo. Justificativa: Visto que a mastectomia radical causa diversas disfunções cinético-funcionais em membro superior, a pesquisa busca desenvolver uma revisão de literatura, onde aborda e averigua as técnicas de cinesioterapia e terapia complexa descongestiva no tratamento fisioterapêutico. Objetivo: Apresentar os benefícios da cinesioterapia e terapia complexa descongestiva no pós-operatório de mastectomia radical em mulheres. Metodologia: Foi elaborada a partir da revisão bibliográfica, nas seguintes bases de dados: Google Acadêmico, SCIELO, Instituto Nacional do Câncer (INCA), Biblioteca Virtual em Saúde (BVS), Medline e LILACS, com os descritores Mastectomia Radical e Fisioterapia, tendo como critério de inclusão, trabalhos publicados no período de 2000 a 2021, nos idiomas em inglês e português, excluindo-se os artigos em duplicidade, que não se referiam ao tema; não disponíveis na íntegra; artigos sem abordagem fisioterapêutica e cirurgias de reconstrução mamaria. Resultados: A pesquisa resultou em 50 manuscritos relacionados às estratégias de buscas empregadas. Após os critérios de elegibilidade, 16 estudos foram considerados para serem analisados. Discussão: Diante do estudo realizado, a mastectomia radical demonstra ser uma cirurgia agressiva, causando múltiplas disfunções. Neste contexto a fisioterapia participa na prevenção de complicações pós-cirúrgicas e reabilitação. Segundo os autores, ambas as técnicas de cinesioterapia e CDT, contribuíram para ganho ADM, melhoria na força muscular, diminuição de linfedema, redução da dor, aderências cicatriciais, e a recuperação das atividades funcionais. É de suma importância o acompanhamento fisioterapêutico nos pós-operatório de mastectomia radical, pois não somente reabilita as pacientes mais traz sua autoestima. Conclusão: Concluímos que tanto a cinesioterapia e terapia complexa descongestiva são de grande ajuda quando aplicada junto a outros procedimentos fisioterapêuticos e de forma precoce no pós-operatório de mastectomia radical em mulheres

Acute lymphoblastic leukemia subsequent to temozolomide use in a 26-year-old man: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the development of acute lymphoblastic leukemia in a patient in whom temozolomide was used for the treatment of a brain tumor. Unlike that of other alkylating agents, the leukemogenic potential of temozolomide is considered to be very low, and very rarely are such cases reported.</p> <p>Case Presentation</p> <p>A 26-year-old Pakistani man who was treated for glioblastoma with temozolomide in an adjuvant setting was diagnosed to have acute lymphoblastic leukemia one year after stopping temozolomide.</p> <p>Conclusion</p> <p>Temozolomide is a highly active agent, used in the management of high-grade brain neoplasms. The agent is generally regarded to be safe, with an acceptable safety profile. Very few cases of myelodysplasia associated with temozolomide use have been reported. We report here the first case of acute lymphoblastic leukemia, which developed in a young man about one year after he finished taking temozolomide. This should provide further insight into a possible toxicity profile of this alkylating agent. This finding should be of interest to physicians in general and to medical oncologists in particular.</p