Correction: Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms.

Correction for 'Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms' by Lydia W. Njenga et al., Dalton Trans., 2023, 52, 5823-5847, https://doi.org/10.1039/D3DT00366C.

"I Am Now Five Steps Ahead": How Co-design Platforms Sustain Kenyan Community Health Volunteer Engagement.

OBJECTIVES: The aim of this study is to examine how humancentered design (HCD) as a platform for co-production might function to explain community health volunteer (CHV) motivation in self-directed and self-funded community health activities. Sustaining engagement has been difficult for CHVs who lack monetary incentives, expense reimbursement, and are rarely given opportunity to give their own voice to local health priorities. DESIGN: Qualitative study utilized focus group discussions 12 months post intervention and included both an inductive and deductive level of analysis. SETTING: Three community health units (CHU) representing Kenya's diversity were selected with the local Ministry of Health including peri-urban slum, rural agrarian, and a unit where informal day labor and rented housing was the norm. PARTICIPANTS: The participants were selected according to Kenya's community health strategy norms and had previously had the standard basic community health training. INTERVENTION: A 3-day training rooted in HCD utilized multiple quality improvement tools (asset mapping, root cause analysis, key drivers) in order to help CHVs uncover unarticulated community needs and assumptions and encourage behavior change. Action plans with Plan-Do-Study-Act cycles were tracked longitudinally. RESULTS: Key themes were self-interest, common goal, gratitude/indebtedness. Additional thematic analysis identified altruism as supporting sustained engagement. CONCLUSIONS: This study supports HCD as a platform for sustained CHV engagement. It builds the evidence for self-interest, common goal, and gratitude/indebtedness as sustaining factors. These factors are also seen in process-based theories that operationalize and measure trust building reciprocity cycles that mirror the iterative P-D-S-A cycles seen in HCD.

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms.

The platinum drug, cisplatin, is considered as among the most successful medications in cancer treatment. However, due to its inherent toxicity and resistance limitations, research into other metal-based non-platinum anticancer medications with diverse mechanisms of action remains an active field. In this regard, copper complexes feature among non-platinum compounds which have shown promising potential as effective anticancer drugs. Moreover, the interesting discovery that cancer cells can alter their copper homeostatic processes to develop resistance to platinum-based treatments leads to suggestions that some copper compounds can indeed re-sensitize cancer cells to these drugs. In this work, we review copper and copper complexes bearing dithiocarbamate ligands which have shown promising results as anticancer agents. Dithiocarbamate ligands act as effective ionophores to convey the complexes of interest into cells thereby influencing the metal homeostatic balance and inducing apoptosis through various mechanisms. We focus on copper homeostasis in mammalian cells and on our current understanding of copper dysregulation in cancer and recent therapeutic breakthroughs using copper coordination complexes as anticancer drugs. We also discuss the molecular foundation of the mechanisms underlying their anticancer action. The opportunities that exist in research for these compounds and their potential as anticancer agents, especially when coupled with ligands such as dithiocarbamates, are also reviewed.

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy.

Solid tumors have a unique tumor microenvironment (TME), which includes hypoxia, low acidity, and high hydrogen peroxide and glutathione (GSH) levels, among others. These unique factors, which offer favourable microenvironments and nourishment for tumor development and spread, also serve as a gateway for specific and successful cancer therapies. A good example is metal peroxide structures which have been synthesized and utilized to enhance oxygen supply and they have shown great promise in the alleviation of hypoxia. In a hypoxic environment, certain oxygen-dependent treatments such as photodynamic therapy and radiotherapy fail to respond and therefore modulating the hypoxic tumor microenvironment has been found to enhance the antitumor impact of certain drugs. Under acidic environments, the hydrogen peroxide produced by the reaction of metal peroxides with water not only induces oxidative stress but also produces additional oxygen. This is achieved since hydrogen peroxide acts as a reactive substrate for molecules such as catalyse enzymes, alleviating tumor hypoxia observed in the tumor microenvironment. Metal ions released in the process can also offer distinct bioactivity in their own right. Metal peroxides used in anticancer therapy are a rapidly evolving field, and there is good evidence that they are a good option for regulating the tumor microenvironment in cancer therapy. In this regard, the synthesis and mechanisms behind the successful application of metal peroxides to specifically target the tumor microenvironment are highlighted in this review. Various characteristics of TME such as angiogenesis, inflammation, hypoxia, acidity levels, and metal ion homeostasis are addressed in this regard, together with certain forms of synergistic combination treatments.

Coping with COVID: Developing a Rapid-cycle Frontline Quality-improvement Process to Support Employee Well-being and Drive Institutional Responsiveness in a Tertiary Care Faith-based Hospital in Rural Kenya.

The coronavirus disease 2019 (COVID-19) pandemic has demanded rapid institutional responses to meet the needs of patients and employees in the face of a serious new disease. To support the well-being of frontline staff, a series of debriefing sessions was used to drive a rapid-cycle quality-improvement process. The goals were to confidentially determine personal coping strategies used by staff, provide an opportunity for staff cross-learning, identify what staff needed most, and provide a real-time feedback loop for decision-makers to create rapid changes to support staff safety and coping. Data were collected via sticky notes on flip charts to protect confidentiality. Management reviewed the data daily. Institutional responses to problems identified during debrief sessions were tracked, visualized, addressed, and shared with staff. More than 10% of staff participated over a 2-week period. Feedback influenced institutional decisions to improve staff schedules, transportation, and COVID-19 training.

Beyond DNA-targeting in Cancer Chemotherapy. Emerging Frontiers - A Review.

Modern anti-cancer drugs target DNA specifically for rapid division of malignant cells. One downside of this approach is that they also target other rapidly dividing healthy cells, such as those involved in hair growth leading to serious toxic side effects and hair loss. Therefore, it would be better to develop novel agents that address cellular signaling mechanisms unique to cancerous cells, and new research is now focussing on such approaches. Although the classical chemotherapy area involving DNA as the set target continues to produce important findings, nevertheless, a distinctly discernible emerging trend is the divergence from the cisplatin operation model that uses the metal as the primary active center of the drug. Many successful anti-cancer drugs present are associated with elevated toxicity levels. Cancers also develop immunity against most therapies and the area of cancer research can, therefore, be seen as an area with a high unaddressed need. Hence, ongoing work into cancer pathogenesis is important to create accurate preclinical tests that can contribute to the development of innovative drugs to manage and treat cancer. Some of the emergent frontiers utilizing different approaches include nanoparticles delivery, use of quantum dots, metal complexes, tumor ablation, magnetic hypothermia and hyperthermia by use of Superparamagnetic Iron oxide Nanostructures, pathomics and radiomics, laser surgery and exosomes. This review summarizes these new approaches in good detail, giving critical views with necessary comparisons. It also delves into what they carry for the future, including their advantages and disadvantages.

Implementation research and human-centred design: how theory driven human-centred design can sustain trust in complex health systems, support measurement and drive sustained community health volunteer engagement.

Human-centred design (HCD) can support complex health system interventions by navigating thorny implementation problems that often derail population health efforts. HCD is a pragmatic, 'practice framework', not an intervention protocol. It can build empathy by bringing patient voice, user perspective and innovation to construct and repair pieces of the intervention or health system. However, its emphasis on product development and process change with fixed end points has left it as an approach lacking explanatory power and reproducible measurement. Yet when informed by theory, the tremendous innovation potential of HCD can be harnessed to drive sustainability, mediate implementation problems, frame measurement constructs and ultimately improve population-level health outcomes. In attempting to mine, the potential of HCD we move beyond the pragmatic 'how it works', to the theoretical question, 'why it works'. In doing so, we explore a more fundamental human question, 'How can participation and engagement be sustained for impact in close to the community health systems?' In this exploration, we illustrate the power of HCD by linking it to our theory of trust building. The research method we utilize is that of a longitudinal process evaluation. We leverage the heterogeneity of five community health units from the diverse setting (rural, peri-urban slum) to better understand what works for whom and in what context by tracking 21 groups of community health volunteers (CHVs) over 12 months. We report results with a focus on the outlier case failure to illustrate the contrast with common features of sustained CHV engagement, where recurrent reciprocal cycles of trust building are demonstrated in the successful implementation of action plans in plan-do-study-act cycles for improvement. All was accomplished by CHVs with no external funding. We conclude by discussing how HCD could be unleashed if linked to theoretical frameworks, increasing ability to address implementation challenges in complex health systems.

New Palladium(II) and Platinum(II) Complexes Based on Pyrrole Schiff Bases: Synthesis, Characterization, X-ray Structure, and Anticancer Activity.

New palladium (Pd)II and platinum (Pt)II complexes (C1-C5) from the Schiff base ligands, R-(phenyl)methanamine (L1), R-(pyridin-2-yl)methanamine (L2), and R-(furan-2-yl)methanamine (L3) (R-(E)-N-((1H-pyrrol-2-yl) methylene)) are herein reported. The complexes (C1-C5) were characterized by FTIR, 1H and 13C NMR, UV-vis, and microanalyses. Single-crystal X-ray crystallographic analysis was performed for the two ligands (L1-L2) and a Pt complex. Both L1 and L2 belong to P21/n monoclinic and P-1 triclinic space systems, respectively. The complex C5 belongs to the P21/c monoclinic space group. The investigated molar conductivity of the complexes in DMSO gave the range 4.0-8.8 µS/cm, suggesting neutrality, with log P values ≥ 1.2692 ± 0.004, suggesting lipophilicity. The anticancer activity and mechanism of the complexes were investigated against various human cancerous (Caco-2, HeLa, HepG2, MCF-7, and PC-3) and noncancerous (MCF-12A) cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Apopercentage assays, respectively. C5 demonstrated strong DNA-binding affinity for calf thymus DNA (CT-DNA) with a binding constant of 8.049 × 104 M-1. C3 reduced cell viability of all the six cell lines, which included five cancerous cell lines, by more than 80%. The C5 complex also demonstrated remarkably high selectivity with no cytotoxic activity toward the noncancerous breast cell line but reduced the viability of the five cancerous cell lines, which included one breast cancer cell line, by more than 60%. Further studies are required to evaluate the selective toxicity of these two complexes and to fully understand their mechanism of action.

Improving maternal and newborn health: effectiveness of a community health worker program in rural Kenya.

BACKGROUND: Volunteer community health workers (CHWs) form an important element of many health systems, and in Kenya these volunteers are the foundation for promoting behavior change through health education, earlier case identification, and timely referral to trained health care providers. This study examines the effectiveness of a community health worker project conducted in rural Kenya that sought to promote improved knowledge of maternal newborn health and to increase deliveries under skilled attendance. METHODS: The study utilized a quasi-experimental nonequivalent design that examined relevant demographic items and knowledge about maternal and newborn health combined with a comprehensive retrospective birth history of women's children using oral interviews of women who were exposed to health messages delivered by CHWs and those who were not exposed. The project trained CHWs in three geographically distinct areas. RESULTS: Mean knowledge scores were higher in those women who reported being exposed to the health messages from CHWs, Eburru 32.3 versus 29.2, Kinale 21.8 vs 20.7, Nyakio 26.6 vs 23.8. The number of women delivering under skilled attendance was higher for those mothers who reported exposure to one or more health messages, compared to those who did not. The percentage of facility deliveries for women exposed to health messages by CHWs versus non-exposed was: Eburru 46% versus 19%; Kinale 94% versus 73%: and Nyakio 80% versus 78%. CONCLUSION: The delivery of health messages by CHWs increased knowledge of maternal and newborn care among women in the local community and encouraged deliveries under skilled attendance.