RESUMO
Background and Objective: Public health nurses (PHNs) are vital in the local implementation of the provisions of the Universal Healthcare (UHC) Act of 2019. However, they need adequate competencies in health systems approach to successfully implement the provisions of the law. In response to this, a leadership development course for public health nurses (LDC-PHN), anchored on the building blocks of health systems, was developed and implemented. This paper aims to describe the extent to which training participants have applied the competencies acquired from the LDC-PHN as manifested by the workplace application of their capstone projects. Methods: Following Kirkpatrick's Model of Evaluation, we used a multi-method study design to evaluate the extent of the participants' workplace application of acquired competencies. Sources of data included the Workplace Application Plan (WAP) accomplished by each participant, a questionnaire to determine the perceived implementation status of the participants' capstone project, interviews, and focus group discussions (FGDs) conducted with selected participants and their supervisors, and observation visits. Data were collected from May to December 2022. Data from the semistructured interviews and FGDs were analyzed through content analysis, while the participants' perceived status of their capstone project implementation was summarized as frequencies. Results: Majority of the participants (61.9%) reported partial implementation of their capstone project while 16.77% reported full implementation. Capstone project implementation was facilitated by the support received from their supervisors and local chief executives. Barriers identified included the demands of the COVID-19 pandemic and the challenges imposed by the events before and after the 2022 Philippine National elections. Major themes emerged from the interviews conducted among participants and their supervisors. The workplace application of the training program outcomes, based on participants' perspectives, yielded increased capacity to lead and innovate, improved ability to advocate for capstone project implementation, transferability of acquired skill sets, and improved population outcomes. From supervisors' perspectives, workplace application of training program outcomes include increased ability of PHNs to deliver health services, and visible enhancement of leadership and supervision skills among PHNs. Conclusion: Given ample support and opportunities, and despite the barriers and challenges they faced, LDC-PHN participants, in general, utilized and applied the competencies they gained from the course in their actual work setting. Course graduates participated in health systems strengthening at various capacities by acting upon their capstone projects that addressed UHC challenges within their particular work settings.
RESUMO
Many biological mechanisms rely on the precise control of conformational changes in proteins. Understanding such dynamic processes requires methods for determining structures and their temporal evolution. In this study, we introduce a novel approach to time-resolved ion mobility mass spectrometry. We validated the method on a simple photoreceptor model and applied it to a more complex system, the animal-like cryptochrome from Chlamydomonas reinhardtii (CraCRY), to determine the role of specific amino acids affecting the conformational dynamics as reaction to blue light activation. In our setup, using a high-power LED mounted in the source region of an ion mobility mass spectrometer, we allow a time-resolved evaluation of mass and ion mobility spectra. Cryptochromes like CraCRY are a widespread type of blue light photoreceptors and mediate various light-triggered biological functions upon excitation of their inbuilt flavin chromophore. Another hallmark of cryptochromes is their flexible carboxy-terminal extension (CTE), whose structure and function as well as the details of its interaction with the photolyase homology region are not yet fully understood and differ among different cryptochromes types. Here, we addressed the highly conserved C-terminal domain of CraCRY, to study the effects of single mutations on the structural transition of the C-terminal helix α22 and the attached CTE upon lit-state formation. We show that D321, the putative proton acceptor of the terminal proton-coupled electron transfer event from Y373, is essential for triggering the large-scale conformational changes of helix α22 and the CTE in the lit state, while D323 influences the timing.
Assuntos
Chlamydomonas reinhardtii , Criptocromos , Conformação Proteica , Criptocromos/química , Criptocromos/metabolismo , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/metabolismo , Espectrometria de Massas/métodos , Espectrometria de Mobilidade Iônica/métodos , Modelos MolecularesRESUMO
A series of cinnamylideneacetophenones were synthesized via a modified Claisen-Schmidt condensation reaction and evaluated for cytotoxicity against breast cancer cells using the Alamar Blue™ assay. Derivatives 17 and 18 bearing a 2-nitro group on the B ring, exhibited sub-micromolar cytotoxicity in MCF-7 cells (IC50=71 and 1.9 nM), respectively. Derivative 17 also displayed sub-micromolar (IC50=780 nM) cytotoxicity in MDA-MB-468 cells. Additionally, 17 and 18 displayed significantly less cytotoxicity than the chemotherapeutic doxorubicin in non-tumorigenic MCF-10A cells. This study provides evidence supporting the continued development of nitro-substituted cinnamylideneacetophenones as small molecules to treat breast cancer.