Curcumins and its derivatives as potential inhibitors of New Coronavirus (COVID-19) main protease: an in silico strategy

Coronavirus (COVID-19) disease outbreak caused a worldwide pandemic with a powerful lethal potential and still, there is no specific treatment to it. Natural bioactive molecules like curcumins were investigated in this work aiming to block the active site of COVID-19 Main protease (Mpro), since they present several biological activities, being more suitable in terms of fewer side effects, once this disease overloads the immune system of patients. Hereby, curcumin and several derivatives were screened for their ability to react with Mpro receptors (PDB: 6LU7). N3, Azithromycin (AZT), and Baracitinib (BRT) were evaluated as positive controls and in combined therapeutics possibilities with curcumins. N3, AZT, and BRT bound to different protein receptors, and also it was observed that N3 bound in the same site as hexahydrocurcumin and curcumin glucuronide bound at the AZT’s site and bisdemethoxycurcumin, curcumin, curcumin sulfate, cyclocurcumin, demethoxycurcumin, dihydrocurcumin and hexahydrocurcuminol bound at BRT’s site. All molecules analyzed have high force interaction fields. Once the viral activity is mainly intracellular, these compounds also were evaluated for their hydropathic abilities. All molecules were classified and considered capable of membrane cell invading. These results suggest that the therapeutic approach of the curcumin derivatives associated with AZT and the antiviral inhibitor N3 is promissory for future evaluation of their synergism in in vitro and in vivo tests to define their additional viability in the treatment of COVID-19.

Pathway to the Transformative Policy of Agenda 2030: Evaluation of Finland’s Sustainable Development Policy

Finland has been the first country in the world to conduct a comprehensive evaluation of the national implementation the Agenda 2030. The purpose of the evaluation was to support efficient implementation of the agenda by producing information on the nation’s sustainability work for all administrative branches. The evaluation results are used for coherence in the policies and long-term sustainable development activities. The evaluation produced concrete recommendations on future directions for sustainable development policy. It also proposed future evaluation approaches.In this chapter, the authors present the evaluation approach and discuss the key results and their usage. They identify the essential elements of the utility of the evaluation in contributing to national progress of sustainable development policy. The Agenda 2030 evaluation approach was developmentally oriented and conducted in a very participatory manner. The authors reflect on the evaluative lessons learned and future options. They encourage emphasis on learning throughout the evaluation process even more in policy-level evaluations, and special attention to usefulness of the evaluation results already in evaluation design. Designing inclusive evaluation processes is a crucial precondition for evidence-informed learning and decision making in promoting transformative policy in the country context.

Business Model Creation for Cost Saving in the New World Economic Order

Globalization and economy features in this new world economic order due to SARS-CoV-2 pandemic crisis involve taking into account new ideas and proposals to keep the market share and to fight against competition. It is very important to consider and evaluate the business model of a company to drive all the objectives and the strategy towards the aimed position in the market to assure the market share in the future. Evaluation and analysis of a business model, together with new proposals regarding it may help a company to achieve all the objectives and to increase its competitiveness in the market.

Harnessing the Potential of miRNAs in Malaria Diagnostic and Prevention

Despite encouraging progress over the past decade, malaria remains a major global health challenge. Its severe form accounts for the majority of malaria-related deaths, and early diagnosis is key for a positive outcome. However, this is hindered by the non-specific symptoms caused by malaria, which often overlap with those of other viral, bacterial and parasitic infections. In addition, current tools are unable to detect the nature and degree of vital organ dysfunction associated with severe malaria, as complications develop silently until the effective treatment window is closed. It is therefore crucial to identify cheap and reliable early biomarkers of this wide-spectrum disease. microRNAs (miRNAs), a class of small non-coding RNAs, are rapidly released into the blood circulation upon physiological changes, including infection and organ damage. The present review details our current knowledge of miRNAs as biomarkers of specific organ dysfunction in patients with malaria, and both promising candidates identified by pre-clinical models and important knowledge gaps are highlighted for future evaluation in humans. miRNAs associated with infected vectors are also described, with a view to expandind this rapidly growing field of research to malaria transmission and surveillance.

Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients

Background Both human and veterinary cancer chemotherapy are undergoing a paradigm shift from a “one size fits all” approach to more personalized, patient-oriented treatment strategies. Personalized chemotherapy is dependent on the identification and validation of biomarkers that can predict treatment outcome and/or risk of toxicity. Many cytotoxic chemotherapy agents, including doxorubicin, base their mechanism of action by interaction with DNA and disruption of normal cellular processes. We developed a high-resolution/accurate-mass liquid chromatography-mass spectrometry DNA screening approach for monitoring doxorubicin-induced DNA modifications (adducts) in vitro and in vivo. We used, for the first time, a new strategy involving the use of isotope-labeled DNA, which greatly facilitates adduct discovery. The overall goal of this work was to identify doxorubicin-DNA adducts to be used as biomarkers to predict drug efficacy for use in veterinary oncology. Results We used our novel mass spectrometry approach to screen for adducts in purified DNA exposed to doxorubicin. This initial in vitro screening identified nine potential doxorubicin-DNA adduct masses, as well as an intense signal corresponding to DNA-intercalated doxorubicin. Two of the adduct masses, together with doxorubicin and its metabolite doxorubicinol, were subsequently detected in vivo in liver DNA extracted from mice exposed to doxorubicin. Finally, the presence of these adducts and analytes was explored in the DNA isolated from dogs undergoing treatment with doxorubicin. The previously identified nine DOX-DNA adducts were not detected in these preliminary three samples collected seven days post-treatment, however intercalated doxorubicin and doxorubicinol were detected. Conclusions This work sets the stage for future evaluation of doxorubicin-DNA adducts and doxorubicin-related molecules as candidate biomarkers to personalize chemotherapy protocols for canine cancer patients. It demonstrates our ability to combine in one method the analysis of DNA adducts and DNA-intercalated doxorubicin and doxorubicinol. The last two analytes interestingly, were persistent in samples from canine patients undergoing doxorubicin chemotherapy seven days after treatment. The presence of doxorubicin in all samples suggests a role for it as a promising biomarker for use in veterinary chemotherapy. Future studies will involve the analysis of more samples from canine cancer patients to elucidate optimal timepoints for monitoring intercalated doxorubicin and doxorubicin-DNA adducts and the correlation of these markers with therapy outcome.

Cue-based versus scheduled feeding for preterm infants transitioning from tube to oral feeding: the Cubs mixed-methods feasibility study

Background There is a lack of evidence of the effect of cue-based feeding compared with scheduled feeding on important outcomes for preterm infants. Objectives The objectives were as follows: (1) to describe the characteristics, components, theoretical basis and outcomes of approaches to feeding preterm infants transitioning from tube to oral feeding; (2) to identify operational policies, barriers and facilitators, and staff and parents’ educational needs in neonatal units implementing cue-based feeding; (3) to co-produce an intervention for feeding preterm infants in response to feeding cues; (4) to appraise the willingness of parents and staff to implement and sustain the intervention; (5) to assess associated costs of implementing cue-based feeding; (6) to determine the feasibility and acceptability of a future trial; (7) to scope existing data-recording systems and potential outcome measures; and (8) to determine stakeholders’ views of whether or not a randomised controlled trial of this approach is feasible. Design This was a mixed-methods intervention development and feasibility study comprising (1) a systematic review, case studies, qualitative research and stakeholder consensus; (2) the co-production of the intervention; (3) a mixed-methods feasibility study; and (4) an assessment of stakeholder preferences for a future evaluation. Setting Three neonatal units in the UK (two level 3 units and one level 2 unit). Participants Developmentally normal, clinically stable preterm infants receiving enteral feeds (n = 50), parents (n = 15 pre intervention development; n = 14 in the feasibility study) and health-care practitioners (n = 54 pre intervention development; n = 16 in the feasibility study). Intervention An evidence-informed multicomponent intervention comprising training, a feeding protocol, feeding assessment tools, supplementary training materials [including posters, a film and a narrated PowerPoint (Microsoft Corporation, Redmond, WA, USA) presentation] and the ‘Our Feeding Journey’ document. Main outcome measures The main outcome measures were recruitment and screening rates, infant weight gain, duration of the intervention, feeding outcomes, implementation outcomes (contextual facilitators and barriers, acceptability, adoption, appropriateness and fidelity) and stakeholder preferences for a future evaluation. Results The systematic review of 25 studies concluded that evidence in favour of cue-based feeding should be treated cautiously. The case studies and qualitative research highlighted contextual barriers to and facilitators of the implementation of cue-based feeding. The telephone survey found that many neonatal units are considering implementing cue-based feeding. We recruited 37% of eligible infants, and there was good retention in the study until discharge but a high loss to follow-up at 2 weeks post discharge. The mean number of days from intervention to transition to full oral feeding was 10.8, and the mean daily change in weight gain was 25 g. The intervention was acceptable to parents and staff, although there was dissatisfaction with the study documentation. Intervention training did not reach all staff. A cluster-randomised design with a composite outcome was suggested by stakeholders for a future study. Limitations The intervention was available only in English. Intervention training did not reach all staff. There was low recruitment to qualitative interviews and observations. Only a small number of medical staff engaged in either the training or the interviews. Conclusions It is feasible to implement a cue-based feeding intervention with improved training and documentation. Further work is needed to assess the feasibility of a future trial, noting evidence of existing lack of equipoise. Future work The next steps are to digitalise the intervention and conduct a survey of all neonatal units in the UK. Study registration This study is registered as PROSPERO CRD42018097317 and ISRCTN13414304. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 74. See the NIHR Journals Library website for further project information.

Updated Global Fuel Exploitation Inventory (GFEI) for methane emissions from the oil, gas, and coal sectors: evaluation with inversions of atmospheric methane observations

We present an updated version of the Global Fuel Exploitation Inventory (GFEI) for methane emissions and evaluate it with results from global inversions of atmospheric methane observations from satellite (GOSAT) and in situ platforms (GLOBALVIEWplus). GFEI allocates methane emissions from oil, gas, and coal sectors and subsectors to a 0.1° × 0.1° grid by using the national emissions reported by individual countries to the United Nations Framework Convention on Climate Change (UNFCCC) and mapping them to infrastructure locations. Our updated GFEI v2 gives annual emissions for 2010–2019 that incorporate the most recent UNFCCC national reports, new oil/gas well locations, and improved spatial distribution of emissions for Canada, Mexico, and China. Russia's oil/gas emissions decrease by 83 % in its latest UNFCCC report while Nigerian emissions increase sevenfold, reflecting changes in assumed emission factors. Global gas emissions in GFEI v2 show little net change from 2010 to 2019 while oil emissions decrease and coal emissions slightly increase. Global emissions in GFEI v2 are lower than the EDGAR v6 and IEA inventories for all sectors though there is considerable variability in the comparison for individual countries. GFEI v2 estimates higher emissions by country than the Climate TRACE inventory with notable exceptions in Russia, the US, and the Middle East. Inversion results using GFEI as a prior estimate confirm the lower Russian emissions in the latest UNFCCC report but Nigerian emissions are too high. Oil/gas emissions are generally underestimated by the national inventories for the highest emitting countries including the US, Venezuela, Uzbekistan, Canada, and Turkmenistan. Offshore emissions in GFEI tend to be overestimated. Our updated GFEI v2 provides a platform for future evaluation of national emission inventories reported to the UNFCCC using the newer generation of satellite instruments such as TROPOMI with improved coverage and spatial resolution. It responds to recent aspirations of the Intergovernmental Panel on Climate Change (IPCC) to integrate top-down and bottom-up information into the construction of national emission inventories.

Mining Anti-Inflammation Molecules From Nippostrongylus brasiliensis-Derived Products Through the Metabolomics Approach

Hookworm is one type of soil-transmitted helminth, which could exert an anti-inflammatory effect in human or animal host, which provides a beneficial possibility for the discovery of inflammatory-related disease interventions. The identification of hookworm-derived anti-inflammatory molecules is urgently needed for future translational research. The emergence of metabolomics has become a powerful approach to comprehensively characterize metabolic alterations in recent times. Herein, excretory and secretory products (ESPs) were collected from cultured adult worm, while small intestinal contents were obtained from Nippostrongylus brasiliensis (N. brasiliensis, Nb)-infected mice. Through ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) platform, metabolomics analysis was used to explore the identification of anti-inflammatory molecules. Out of 45 differential metabolites that were discovered from ESPs, 10 of them showed potential anti-inflammatory properties, which could be subclassed into amino acids, furanocoumarins, linear diarylheptanoids, gamma butyrolactones, and alpha-keto acids. In terms of intestinal contents that were derived from N. brasiliensis-infected mice, 14 out of 301 differential metabolites were discovered to demonstrate anti-inflammatory effects, with possible subclassification into amino acids, benzylisoquinolines, quaternary ammonium salts, pyrimidines, pregnane steroids, purines, biphenyls, and glycerophosphocholines. Furthermore, nine of the differential metabolites appeared both in ESPs and infected intestinal contents, wherein four were proven to show anti-inflammation properties, namely, L-glutamine, glutamine (Gln), pyruvate, and alanine-Gln (Ala-Gln). In summary, we have provided a method for the identification and analysis of parasite-derived molecules with potential anti-inflammatory properties in the present study. This array of anti-inflammatory metabolites could provide clues for future evaluation and translational study of these anti-inflammatory molecules.

Teleoncology Orientation of Low-Income Breast Cancer Patients during the COVID-19 Pandemic: Feasibility and Patient Satisfaction

Objective The present study aims to assess the feasibility and patient satisfaction of teleoncology orientation in a vulnerable population of breast cancer patients assessed in a government health system during the coronavirus pandemic in 2020. Methods Eligible patients received an invitation to receive remote care to minimize exposure to an environment in which the risk of respiratory infection was present. The means of communication was telephone through an application that allows free conversation with no charge. An anonymous-response questionnaire based on a Likert-type scale was sent through a cell phone application or e-mail directly to each patient or close relative of the patient immediately after teleconsultation. Responses to the questions, which addressed utility, facility, interface quality, interaction quality, reliability, satisfaction, and interest in future evaluation, were compiled and analyzed. Results A total of 176 eligible patients scheduled for consultation were evaluated and 98 were included. Seventy (71.4%) successfully undertook the teleorientation. The questionnaire was submitted by 43 (61.4%) patients. The overall teleoncology orientation was classified as very positive by 41 (95.3%) patients. Specifically, regarding the questionnaire items, 43 (100%) patients scored 4 or 5 (agreed that the teleconsultation was beneficial) concerning the facility, followed by 42 (97.2%) for the interface quality, 41 (95.3%) for both utility and interaction quality, 40 (93%) for satisfaction and interest in future evaluation, and, finally, 39 (90.6%) for reliability. Conclusion Teleoncology orientation of low-income breast cancer patients is most feasible and leads to high patient satisfaction.