Research attitudes, practice and literacy among Kenyan palliative care healthcare professionals: an observational, crosssectional online survey

Background: While research is needed to advocate for implementation of global agendas to strengthen palliative care, healthcare professionals’ research literacy must improve to bridge the gap between evidence and practice. A resurgent focus on North-South power disparities, means attention should also focus on understanding low- and middle-income countries’ local agency to implement palliative care research agendas. Methods: An observational, cross-sectional online survey among Kenyan palliative healthcare professionals currently working at any of the palliative and hospice care organizations operational during January – December 2019, using descriptive statistics. Results: Among the 93 survey respondents, participants were mainly nurses (50.54%; n=47). Regarding research attitudes: all agreed/strongly agreed research was important for their professional work. Over nine-tenths (91.21%; n=83) reported having the skills to conduct research, and 91.30% (n=84) wanted to conduct research in their clinical work. 90% (90.21%; n=83) reported supervisory support to conduct research. A comparable proportion (90.22%; n=83) would undertake research if they could find funding. Regarding research practice: over two-thirds (70.65%; n=65) reported ever having had a mentor who encouraged them to do research, while approximately half (50.59%; n=43) reported reading evidence-based journal articles about once per month and attending monthly in-house meetings on palliative care (56.79%; n=46). Regarding research literacy: while over two-fifths of respondents described their current research literacy level as ‘none’ or ‘beginner’ (44.56%; n=41), a comparable proportion described it as ‘intermediate’ (45.65%; n=42), with 9 (9.78%) stating it was ‘advanced’. Conclusion: The majority of palliative healthcare professionals report having interest, skills and support at work to conduct palliative care research, with a low-to-medium level of research literacy. The current study explored palliative care staff attitudes to, experience in, and literacy with the research process, which is necessary to creating a dialogue on implementing research findings. This study also adds to the global empowerment agenda, addressing inequities in research opportunities and local capacity to own and undertake palliative care research

Kenyan palliative care providers’ and leaders’ perceptions of palliative care research needs and support to facilitate rigorous research

Background: Palliative care (PC) can reduce symptom distress and improve quality of life for patients and their families experiencing life-threatening illness. While the need for PC in Kenya is high, PC service delivery and research is limited. Qualitative research is needed to explore potential areas for PC research and support needed to enable that research. This insight is critical for informing a national PC research agenda and mobilizing limited resources for conducting rigorous PC research in Kenya. Objectives: To explore perceptions of priority areas for PC research and support needed to facilitate rigorous research from the perspective of Kenyan PC providers and leaders. Methods: Focus groups (FGs) were conducted in November and December of 2018 using a semi-structured interview guide. FGs were audio-recorded, transcribed, and analyzed using a thematic content analysis approach. Results: Three FGs were conducted (n = 22 participants). Ten themes related to PC research emerged, including research on: 1) beliefs about death, disease, and treatment to inform PC; 2) awareness about PC, 3) integration of PC within the health system; 4) understanding caregiver experiences and needs; 5) community health volunteers (CHVs) and volunteer programs; 6) evaluation of costs and benefits of PC; 7) treatment approaches, including complementary and alternative medicine (CAM) and advanced diagnostics at end of life; 8) other suggestions for research, 9) populations in need of PC research; and 10) resources for enabling research. Conclusions: Kenyan PC providers and leaders identified key areas requiring increased scientific inquiry and critical resources needed to enable this research. These findings can help to focus future PC research in Kenya and encourage funding agencies to prioritize the issues identified

Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.</p> <p>Methods</p> <p>Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. <it>In vivo </it>effect of EGCG on tumor growth was examined in a xenograft model.</p> <p>Results</p> <p>Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H₂O₂, 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.</p> <p>Conclusions</p> <p>Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.</p

Screening for Active Small Molecules in Mitochondrial Complex I Deficient Patient's Fibroblasts, Reveals AICAR as the Most Beneficial Compound

Congenital deficiency of the mitochondrial respiratory chain complex I (CI) is a common defect of oxidative phosphorylation (OXPHOS). Despite major advances in the biochemical and molecular diagnostics and the deciphering of CI structure, function assembly and pathomechanism, there is currently no satisfactory cure for patients with mitochondrial complex I defects. Small molecules provide one feasible therapeutic option, however their use has not been systematically evaluated using a standardized experimental system. In order to evaluate potentially therapeutic compounds, we set up a relatively simple system measuring different parameters using only a small amount of patient's fibroblasts, in glucose free medium, where growth is highly OXPOS dependent. Ten different compounds were screened using fibroblasts derived from seven CI patients, harboring different mutations

Glutaredoxin-1 Overexpression Enhances Neovascularization and Diminishes Ventricular Remodeling in Chronic Myocardial Infarction

Oxidative stress plays a critical role in the pathophysiology of cardiac failure, including the modulation of neovascularization following myocardial infarction (MI). Redox molecules thioredoxin (Trx) and glutaredoxin (Grx) superfamilies actively maintain intracellular thiol-redox homeostasis by scavenging reactive oxygen species. Among these two superfamilies, the pro-angiogenic function of Trx-1 has been reported in chronic MI model whereas similar role of Grx-1 remains uncertain. The present study attempts to establish the role of Grx-1 in neovascularization and ventricular remodeling following MI. Wild-type (WT) and Grx-1 transgenic (Grx-1Tg/+) mice were randomized into wild-type sham (WTS), Grx-1Tg/+ Sham (Grx-1Tg/+S), WTMI, Grx-1Tg/+MI. MI was induced by permanent occlusion of the LAD coronary artery. Sham groups underwent identical time-matched surgical procedures without LAD ligation. Significant increase in arteriolar density was observed 7 days (d) after surgical intervention in the Grx-1Tg/+MI group as compared to the WTMI animals. Further, improvement in myocardial functional parameters 30 d after MI was observed including decreased LVIDs, LVIDd, increased ejection fraction and, fractional shortening was also observed in the Grx-1Tg/+MI group as compared to the WTMI animals. Moreover, attenuation of oxidative stress and apoptotic cardiomyocytes was observed in the Grx-1Tg/+MI group as compared to the WTMI animals. Increased expression of p-Akt, VEGF, Ang-1, Bcl-2, survivin and DNA binding activity of NF-κB were observed in the Grx-1Tg/+MI group when compared to WTMI animals as revealed by Western blot analysis and Gel-shift analysis, respectively. These results are the first to demonstrate that Grx-1 induces angiogenesis and diminishes ventricular remodeling apparently through neovascularization mediated by Akt, VEGF, Ang-1 and NF-κB as well as Bcl-2 and survivin-mediated anti-apoptotic pathway in the infarcted myocardium

Mitochondrial Pathway Mediates the Antileukemic Effects of Hemidesmus Indicus, a Promising Botanical Drug

Although cancers are characterized by the deregulation of multiple signalling pathways, most current anticancer therapies involve the modulation of a single target. Because of the enormous biological diversity of cancer, strategic combination of agents targeted against the most critical of those alterations is needed. Due to their complex nature, plant products interact with numerous targets and influence several biochemical and molecular cascades. The interest in further development of botanical drugs has been increasing steadily and the FDA recently approved the first new botanical prescription drug. The present study is designed to explore the potential antileukemic properties of Hemidesmus indicus with a view to contributing to further development of botanical drugs. Hemidesmus was submitted to an extensive in vitro preclinical evaluation.A variety of cellular assays and flow cytometry, as well as a phytochemical screening, were performed on different leukemic cell lines. We have demonstrated that Hemidesmus modulated many components of intracellular signaling pathways involved in cell viability and proliferation and altered the protein expression, eventually leading to tumor cell death, mediated by a loss of mitochondrial transmembrane potential and increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial permeability transition pore inhibitors did not reverse Hemidesmus-induced mitochondrial depolarization. Hemidesmus induced a significant [Ca(2+)](i) raise through the mobilization of intracellular Ca(2+) stores. Moreover, Hemidesmus significantly enhanced the antitumor activity of three commonly used chemotherapeutic drugs (methotrexate, 6-thioguanine, cytarabine). A clinically relevant observation is that its cytotoxic activity was also recorded in primary cells from acute myeloid leukemic patients.These results indicate the molecular basis of the antileukemic effects of Hemidesmus and identify the mitochondrial pathways and [Ca(2+)](i) as crucial actors in its anticancer activity. On these bases, we conclude that Hemidesmus can represent a valuable tool in the anticancer pharmacology, and should be considered for further investigations