RESUMO
Background: Opioid overdose deaths continue to present major public health challenges in the U.S. Harm reduction agencies have begun using drug checking technologies to identify adulterants in the local drug supply and reduce overdose risk among people who use drugs (PWUD). Through qualitative and ethnographic methods, we assess the use of portable mass spectrometers at a harm reduction agency in a Northeastern U.S. city. Methods: We conducted participant observation, and on-the-spot qualitative interviews with harm-reduction staff members (n = 10) and their clientele (n = 17) between May 2019 and December 2020. Interviews explored emic views on drug checking (process, logistics, technology), and perceived benefits and challenges. We used thematic content analysis techniques to code and analyze interview transcriptions. Results: Implementation and use of drug checking devices were not free of challenges and malfunctions, often delaying drug checking opportunities and increasing suspicions and distrust among clients. Yet, staff members perceived that when working properly, or in conjunction with an additional device, they offered information about purchased drugs that could empower clients and potentially lead to positive behavior change. Use of these devices also enhanced engagement between harm reduction staff and PWUD, facilitating meaningful conversations around self-advocacy and harm reduction engagement. Conclusion: We report qualitative findings on the experiences and perceptions of drug checking devices among harm reduction staff and PWUD. Our findings indicate that use of this technology has the potential to decrease risk behaviors, expand health promotion services, and help reduce high rates of fentanyl-related overdose.
Assuntos
Overdose de Drogas , Drogas Ilícitas , Overdose de Opiáceos , Humanos , Fentanila , Overdose de Drogas/prevenção & controle , Saúde Pública , Tecnologia , Redução do Dano , Analgésicos OpioidesRESUMO
NUTM1-rearranged tumors are defined by the presence of a gene fusion between NUTM1 and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. NUTM1-rearranged tumors display histologic features of a poorly differentiated carcinoma with areas of focal squamous differentiation and typically express the BRD4-NUTM1 fusion gene defining a distinct clinicopathologic entity-NUT carcinoma (NC). NCs with mesenchymal differentiation have rarely been described in the literature. In this report, we describe the characterization of two cases of high-grade spindle cell sarcoma harboring a novel MGA-NUTM1 fusion. Whole-genome sequencing identified the presence of complex rearrangements resulting in a MGA-NUTM1 fusion gene in the absence of other significant somatic mutations. Genetic rearrangement was confirmed by fluorescence in situ hybridization, and expression of the fusion gene product was confirmed by transcriptomic analysis. The fusion protein was predicted to retain nearly the entire protein sequence of both MGA (exons 1-22) and NUTM1 (exons 3-8). Histopathologically, both cases were high-grade spindle cell sarcomas without specific differentiation markers. In contrast to typical cases of NC, these cases were successfully treated with aggressive local control measures (surgery and radiation) and both patients remain alive without disease. These cases describe a new subtype of NUTM1-rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of MGA-NUTM1 or alternative NUTM1 gene fusions in the diagnostic workup of high-grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Sarcoma/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores Tumorais/genética , Diferenciação Celular/genética , Criança , Feminino , Fusão Gênica/genética , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Fusão Oncogênica/genética , Recombinação Genética/genética , Sarcoma/metabolismo , Sarcoma Sinovial/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Sequenciamento Completo do Genoma/métodosRESUMO
Human aging is an inevitable and complex phenomenon characterized by a progressive, gradual degradation of physiological and cellular processes that leads from vulnerability to death. Mammalian somatic cells display limited proliferative properties in vitro that results in a process of permanent cell cycle arrest commonly known as senescence. Events leading to cellular senescence are complex but may be due to the increase in tumor suppressor genes, caused by lifetime somatic mutations. Cumulative mutation leaves an imprint on the genome of the cell, an important risk factor for the occurrence of cancer. Adults over the age of 65+ are vulnerable to age related diseases such as cancers but such changes may begin at middle age. MicroRNAs (miRNAs), which are small non-coding RNA, can regulate cancer progression, recurrence and metastasis. This chapter discusses the role of miRNA in tumor microenvironment, consequent to aging.
