AVPCD: a plant-derived medicine database of antiviral phytochemicals for cancer, Covid-19, malaria and HIV.

Serious illnesses caused by viruses are becoming the world's most critical public health issues and lead millions of deaths each year in the world. Thousands of studies confirmed that the plant-derived medicines could play positive therapeutic effects on the patients with viral diseases. Since thousands of antiviral phytochemicals have been identified as lifesaving drugs in medical research, a comprehensive database is highly desirable to integrate the medicinal plants with their different medicinal properties. Therefore, we provided a friendly antiviral phytochemical database AVPCD covering 2537 antiviral phytochemicals from 383 medicinal compounds and 319 different families with annotation of their scientific, family and common names, along with the parts used, disease information, active compounds, links of relevant articles for COVID-19, cancer, HIV and malaria. Furthermore, each compound in AVPCD was annotated with its 2D and 3D structure, molecular formula, molecular weight, isomeric SMILES, InChI, InChI Key and IUPAC name and 21 other properties. Each compound was annotated with more than 20 properties. Specifically, a scoring method was designed to measure the confidence of each phytochemical for the viral diseases. In addition, we constructed a user-friendly platform with several powerful modules for searching and browsing the details of all phytochemicals. We believe this database will facilitate global researchers, drug developers and health practitioners in obtaining useful information against viral diseases.

Fabrication, Physical Characterizations, and In Vitro, In Vivo Evaluation of Ginger Extract-Loaded Gelatin/Poly(Vinyl Alcohol) Hydrogel Films Against Burn Wound Healing in Animal Model.

Crude ginger has been used to treat wounds since ancient times till nowadays. The present study aimed at designing and characterizing topical hydrogel films loaded with ginger extract for wound healing in animal model. The hydrogel films were prepared using PVA and gelatin. The prepared films were evaluated for FTIR analysis, surface morphology, pH, swelling behavior, in vitro release, and % drug content. The wound-healing activity of the extract-loaded hydrogel films was compared with commercially available Silver Sulfadiazine® cream. The drug was compatible with the selected polymers and indicated the suitability of the selected polymers for preparation of topical hydrogel films. The SEM images clearly indicated porous structure of the prepared hydrogel films. Slight changes were observed in pH, ranging from 4.98 ± 0.079 in the beginning of the study to 4.9 ± 0.58 in the end. The swelling percentage after 8 h was 257.7%. The films released 78.7 ± 1.7% of the drug in 250 min. The percent drug content was 97.78 ± 5% which did not change significantly during the storage period. The hydrogel films showed similar wound-healing activity as compared to the commercial product (p > 0.05; ANOVA), while greater wound-healing activity as compared to the control group (p < 0.05; ANOVA) evidenced by intensive collagen formation in histopathological analysis.

Clinically Relevant Cytochrome P450 3A4 Induction Mechanisms and Drug Screening in Three-Dimensional Spheroid Cultures of Primary Human Hepatocytes.

Cytochrome P450 (CYP) 3A4 induction is an important cause of drug-drug interactions, making early identification of drug candidates with CYP3A4 induction liability in drug development a prerequisite. Here, we present three-dimensional (3D) spheroid cultures of primary human hepatocytes (PHHs) as a novel CYP3A4 induction screening model. Screening of 25 drugs (12 known CYP3A4 inducers in vivo and 13 negative controls) at physiologically relevant concentrations revealed a 100% sensitivity and 100% specificity of the system. Three of the in vivo CYP3A4 inducers displayed much higher CYP3A4 induction capacity in 3D spheroid cultures as compared with in two-dimensional (2D) monolayer cultures. Among those, we identified AZD1208, a proviral integration site for Moloney murine leukemia virus (PIM) kinase inhibitor terminated in phase I of development due to unexpected CYP3A4 autoinduction, as a CYP3A4 inducer only active in 3D spheroids but not in 2D monolayer cultures. Gene knockdown experiments revealed that AZD1208 requires pregnane X receptor (PXR) to induce CYP3A4. Rifampicin requires solely PXR to induce CYP3A4 and CYP2B6, while phenobarbital-mediated induction of these CYPs did not show absolute dependency on either PXR or constitutive androstane receptor (CAR), suggesting its ability to switch nuclear receptor activation. Mechanistic studies into AZD1208 uncovered an involvement of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in CYP3A4 induction that is sensitive to the culture format used, as revealed by its inhibition of ERK1/2 Tyrosine 204 phosphorylation and sensitivity to epidermal growth factor (EGF) pressure. In line, we also identified lapatinib, a dual epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) inhibitor, as another CYP3A4 inducer only active in 3D spheroid culture. Our findings offer insights into the pathways involved in CYP3A4 induction and suggest PHH spheroids for preclinical CYP3A4 induction screening.

Aged care clinical mentoring model of change in nursing homes in China: study protocol for a cluster randomized controlled trial.

BACKGROUND: Residents living in nursing homes usually have complex healthcare needs and require a comprehensive care approach to identifying and meeting their care needs. Suboptimal quality of care is reported in nursing homes and is associated with the poor health and well-being of the residents, the burden on acute care hospitals and the high costs of healthcare for the government. The aim of this study is to test the hypothesis that an Aged Care Clinical Mentoring Model will create and sustain evidence-based quality improvement in priority areas and will be cost-effective in nursing homes in Hunan Province, China. METHODS: A cluster randomized controlled trial will be applied to the study. Fourteen nursing homes will be randomly allocated to either the intervention group (n = 7) or the control group (n = 7). Forty staff will be recruited from each nursing home and the estimated sample size will be 280 staff in each group. The intervention includes a structured, evidence-based quality improvement education program for staff to facilitate knowledge translation in evidence-based quality improvement targeting urinary incontinence, pressure injury and falls prevention. The primary outcomes are nursing homes' capacity to create and sustain quality improvement, staff perceptions of person-centered care, self-reported quality of care by residents and selected quality indicators at 12 months follow-up adjusted for baseline value. Secondary outcomes are residents' quality of life, residents' unplanned admissions to acute care hospitals, quality of care reported by staff, staff job satisfaction and staff intention to leave adjusted for baseline value. A mixed linear regression model will be adopted to compare the significant differences between groups over a 12-month period. DISCUSSION: Although the Aged Care Clinical Mentoring Model has been tested as an effective model to bring positive changes in nursing homes in a high-income country, factors affecting the adaptation of the model in nursing homes in low- and middle-income countries are unknown. The carefully planned intervention protocol enables the project team to consider enablers and barriers when adapting the Model. Therefore, strategies and resources will be in place to manage challenges while demonstrating best practice in this study. TRIAL REGISTRATION: Prospectively registered via Chinese Clinical Trial Registry (ChiCTR), ChiCTR-IOC-17013109 , Registered on 25 October 2017.

Human hepatic 3D spheroids as a model for steatosis and insulin resistance.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health concern as reflected in its widespread distribution in the general population. Yet, treatment options are scarce which is at least in part due to lack of reliable human in vitro disease models. Here, we report a human hepatic 3D spheroid system cultured under defined chemical conditions that has the potential to mimic steatotic conditions in a reversible manner, useful for identification of novel drug treatment conditions. Primary human hepatocytes (PHH) from different donors were cultured as spheroid microtissues in physiological in vivo -like culture conditions. Hepatic steatosis was induced over the course of three weeks in culture by supplementing the culture medium with pathophysiological concentrations of free fatty acids, carbohydrates and insulin. Effects of steatosis in the 3D system were evaluated on transcriptional, metabolomic and lipidomic levels. Free fatty acids on one hand as well as a combination of insulin and monosaccharides, promoted lipid accumulation in hepatocytes and increased expression of lipogenic genes, such as fatty acid synthase. This milieu also promoted development of insulin resistance within 2 weeks as manifested by an increase in gluconeogenic and insulin resistance markers, which are observed in type 2 diabetes mellitus and metabolic syndrome. Induced steatosis was reversible after withdrawal of lipogenic substrates and a further reduction in cellular fat content was observed following treatment with different antisteatotic compounds, such as metformin, glucagon, olaparib and antioxidants. Taken together, these results demonstrate that the 3D hepatic spheroids can serve as a valuable, HTS compatible model for the study of liver steatosis and facilitate translational discovery of novel drug targets.

The current practice, preparedness and educational preparation of oncology professionals to provide spiritual care.

AIM: Limited data are available on how spiritual needs of patients with cancer care are addressed by Australian oncologists. The objectives of this study were to explore the current practice, preparedness and education of Australian oncologists and oncology trainees on the provision of spiritual care for their patients with cancer. METHODS: Participants were recruited through oncology professional organizations and data collected through an anonymous online survey using a validated questionnaire. RESULTS: Responses from a total of 69 medical professionals were suitable for data analysis. The majority of the respondents had encountered patients with spiritual care needs during clinical consultations. Only 45% of the respondents perceived that they were able to meet the spiritual needs of their patients. Barriers to providing spiritual care identified a lack of time, education and understanding of spirituality and spiritual care in the context of health. Only 25% stated they had received some form of education on spiritual care with 7% of these stated that the education was adequate. Participants believed that they learnt how to provide spiritual care on the job or because of their self-interest, and not as formal training. CONCLUSION: The results of this study indicate that Australian oncology professionals often encounter patients with spiritual care needs in their clinical practice. Despite this finding, only a small proportion of the medical professionals had education on spiritual care during their professional training. Forty-five percent of the medical practitioners believed that they were able to partly or completely meet their patients' spiritual care needs.

A double-blind randomized controlled trial of normal saline, lactated Ringer's, and hypertonic saline nasal irrigation solution after endoscopic sinus surgery.

BACKGROUND: Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringer's, and hypertonic saline nasal douching solutions after ESS. METHODS: Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center were blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution. RESULTS: Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringer's solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6. CONCLUSION: Douching with lactated Ringer's solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.

Modelling the population-level impact of tai-chi on falls and fall-related injury among community-dwelling older people.

OBJECTIVE: To model the population level impact of tai-chi on future rates of falls and fall-related injury in older people as a tool for policy development. DESIGN: An epidemiological and economic model for estimating population-level effectiveness of tai-chi. SETTING: Australia, 2009. Patients or subjects Australian community-dwelling population aged 70+ years, ambulatory and without debilitating conditions or profound visual defects. Intervention Group-based tai-chi, for 1 h twice weekly for 26 weeks, assuming no sustained effect beyond the intervention period. Main outcome measure Total falls and fall-related hospitalisation prevented in 2009. RESULTS: Population-wide tai-chi delivery would prevent an estimated 5440 falls and 109 fall-related hospitalisations, resulting in a 0.18% reduction in the fall-related hospital admission rate for community-dwelling older people. The gross costs per fall and per fall-related hospital admission prevented were $A4414 (€3013) and $A220,712 (€150,684), respectively. A total investment of $A24.01 million (€16.39 million), equivalent to 4.2% of the cost of fall-related episodes of hospital care in 2003/4, would be required to provide tai-chi for 31,998 people and achieve this effect. CONCLUSIONS: Substantial investment in, and high population uptake of, tai-chi would be required to have a large effect on falls and fall-related hospitalisation rates. Although not accounted for in this study, investment in tai-chi is likely to be associated with additional significant health benefits beyond falls prevention. This approach could be applied to other interventions to assist selection of the most cost-effective falls-prevention portfolio for Australia and other countries.