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Abstract Introduction The poorest in Burkina Faso face numerous barriers to healthcare access, including financial and geographic obstacles, as well as a high burden of chronic conditions and multimorbidity. This study estimates the average cost of providing curative outpatient consultations at first-level healthcare facilities to the poorest in Burkina Faso. It also estimates the budgetary impact of scaling up free access to these services nationwide. The findings provide essential evidence on cost structures to inform decision-makers in developing policies aimed at achieving universal health coverage and ensuring that no one is left behind. Methods We conducted a micro-costing study to estimate the economic costs of providing curative outpatient healthcare services to the poorest at first-level healthcare facilities, considering a health system perspective. We measured the consumption of capital costs (building and equipment) using survey data from 32 primary health facilities and recurrent costs (drugs and consumables) from medical records of 1380 poor patients in Diébougou district. These individuals were targeted and exempted from user fees through a community-based targeting approach. We obtained unit costs from official price lists, pharmacy registries, and expert interviews. We calculated the national budget for providing curative care services to the exempted poorest based on the average cost per first-level consultation. Results The estimated capital and recurrent costs of providing curative care services ranged between USD 0.59 - USD 0.61 and USD 2.58 - USD 5.00, respectively. The total cost ranged between USD 3.17 - USD 5.61 per first-level consultation. Providing curative care to the bottom 20% of the population, assuming 0.25 healthcare contacts per person per year, would result in an annual expense ranging from USD 2.77 M to USD 5.38 M (0.74-1.43% of the healthcare budget in 2019). With 2 healthcare contacts per person per year, costs increase to USD 22.19 M to USD 43.05 M (5.91-11.45% of the healthcare budget). Conclusion The results can inform policies aimed at expanding access to curative care for the poorest in Burkina Faso, contributing to the goals of universal health coverage and leaving no one behind. Further research is needed to enhance cost estimation and budgeting for higher-level care in the country.

Analyzing time series data in industrial settings demands domain knowledge and computer science expertise to develop effective algorithms. AutoML approaches aim to automate this process, reducing human bias and improving accuracy and cost-effectiveness. This article applies an evolutionary algorithm to synthesize recurrent neurons optimized for specific datasets. This adds another layer to the AutoML framework, targeting the internal structure of neurons. We developed an imitation learning control system for an industry CNC machine to enhance operators' productivity. We specifically examine two recorded operator actions: adjusting the engagement rates for linear feed rate and spindle velocity. We compare the performance of our evolved neurons with support vector machine and four well-established neural network models commonly used for time series data: simple recurrent neural networks, long-short-term-memory, independently recurrent neural networks, and transformers. The results demonstrate that the neurons evolved via the evolutionary approach exhibit lower syntactic complexity than LSTMs and achieve lower error rates than other networks. They yield error rates 270% lower for the first operation action, while the error rates are 20% lower for the second action. We also show that our evolutionary algorithm is capable of creating skip-connections and gating mechanisms adapted to the specific characteristics of our dataset.

Background Burkina Faso has been implementing financing reforms towards universal health coverage (UHC) since 2006. Recently, the country introduced a performance-based financing (PBF) program as well as user fee removal (gratuité) policy for health services aimed at pregnant and lactating women and children under 5. We aim to assess the effect of gratuité and PBF policies on facility-based out-of-pocket expenditures (OOPEs) for outpatient services.Methods Our study is a controlled pre- and post-test design using healthcare facility data from the PBF program’s impact evaluation collected in 2014 and 2017. We compared OOPE related to primary healthcare use incurred by children under 5 and individuals above 5 to assess the effect of the gratuité policy on OOPE. We further compared OOPE incurred by individuals residing in PBF districts and non-PBF districts to estimate the effect of the PBF on OOPE. Effects were estimated using difference-in-differences models, distinguishing the estimation of the probability of incurring OOPE from the estimation of the magnitude of OOPE using a generalized linear model (GLM).Results The proportion of children under 5 incurring OOPE declined significantly from 90% in 2014 to 3% in 2017. Concurrently, mean OOPE also decreased. Differences in both the probability of incurring OOPE and mean OOPE between PBF and non-PBF facilities were small. Our difference in differences estimates indicated that gratuité produced an 84% (CI -86%, -81%) reduction in the probability of incurring OOPE and reduced total OOPE by 54% (CI 63%, 42%). We detected no significant effects of PBF, either in reducing the probability of incurring OOPE or in its magnitude.Conclusion User fee removal is an effective demand-side intervention for enhancing financial accessibility. As a supplyside intervention, PBF appears to have limited effects on reducing financial burden.

African swine fever (ASF) is a highly contagious and severe hemorrhagic transboundary swine viral disease with up to a 100% mortality rate, which leads to a tremendous socio-economic loss worldwide. The lack of safe and efficacious ASF vaccines is the greatest challenge in the prevention and control of ASF. In this study, we generated a safe and effective live-attenuated virus (LAV) vaccine candidate VNUA-ASFV-LAVL3 by serially passaging a virulent genotype II strain (VNUA-ASFV-L2) in an immortalized porcine alveolar macrophage cell line (3D4/21, 50 passages). VNUA-ASFV-LAVL3 lost its hemadsorption ability but maintained comparable growth kinetics in 3D4/21 cells to that of the parental strain. Notably, it exhibited significant attenuation of virulence in pigs across different doses (103, 104, and 105 TCID50). All vaccinated pigs remained healthy with no clinical signs of African swine fever virus (ASFV) infection throughout the 28-day observation period of immunization. VNUA-ASFV-LAVL3 was efficiently cleared from the blood at 14–17 days post-infection, even at the highest dose (105 TCID50). Importantly, the attenuation observed in vivo did not compromise the ability of VNUA-ASFV-LAVL3 to induce protective immunity. Vaccination with VNUA-ASFV-LAVL3 elicited robust humoral and cellular immune responses in pigs, achieving 100% protection against a lethal wild-type ASFV (genotype II) challenge at all tested doses (103, 104, and 105 TCID50). Furthermore, a single vaccination (104 TCID50) provided protection for up to 2 months. These findings suggest that VNUA-ASFV-LAVL3 can be utilized as a promising safe and efficacious LAV candidate against the contemporary pandemic genotype II ASFV.

Machilus thunbergii has a history of traditional applications including treating dyspepsia, apoplexy, headaches, abdominal pain, abdominal distension, and leg edema [1]. It is also employed for alleviating allergies, inflammation, pain relief, promoting blood circulation, addressing costal chondritis, and sinusitis [2]. Research into the chemical composition of M. thunbergii has revealed the presence of lignans, flavonoids, lactones, and essential oils [1,3-5]. While some investigations have explored the inhibitory effects of extracts and lignan compounds from this species on NO production [6–8], there has been no research into the flavonoids isolated from this plant and their potential for inhibiting NO production, given our reachable referencing. The ethyl acetate (EtOAc) soluble fraction of M. thunbergii leaves was subjected to column chromatography (CC) using silica gel and Sephadex LH-20 for compound isolation. Nuclear magnetic resonance (NMR) data primarily facilitated the determination of isolated compound structures. Anti-inflammatory activity was evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Anti-inflammatory activity-guided fractionation led to the isolation of twelve secondary metabolites (1−12). The compounds were identified as quercetin (1), kaempferol (2), rhamnetin (3), quercitrin (4), hyperoside (5), reynoutrin (6), guaijaverin (7), afzelin (8), astragalin (9), rutin (10), kaempferol-3-O-rutinoside (11), and rhamnetin-3-O-rutinoside (12). Compounds 3, 5, 6, 9, 11, and 12 were isolated from M. thunbergii for the first time. Evaluation against LPS-induced NO production in macrophage RAW264.7 cells showed that 1−3 exhibited potent inhibitory activity with IC50 values of 15.45, 25.44, and 19.82 µM, respectively. Compounds 4−9 demonstrated IC50 values ranging from 42.15 to 67.42 µM, while 10−12 exhibited inactivity (IC50 > 100 µM).

BackgroundThe COVID-19 pandemic is characterized by rapid increases in infection burden owing to the emergence of new variants with higher transmissibility and immune escape. To date, monitoring the COVID-19 pandemic has mainly relied on passive surveillance, yielding biased epidemiological measures owing to the disproportionate number of undetected asymptomatic cases. Active surveillance could provide accurate estimates of the true prevalence to forecast the evolution of the pandemic, enabling evidence-based decision-making. ObjectiveThis study compared 4 different approaches of active SARS-CoV-2 surveillance focusing on feasibility and epidemiological outcomes. MethodsA 2-factor factorial randomized controlled trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised SARS-CoV-2 prevalence and its precision. The 4 study arms combined 2 factors: individuals versus households and direct testing versus testing conditioned on symptom prescreening. Individuals aged ≥7 years were eligible. Altogether, 27,908 addresses from 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, and a website in 5 languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with reverse transcription loop-mediated isothermal amplification (RT-LAMP); positive and weak results were confirmed with real-time reverse transcription–polymerase chain reaction (RT-PCR). ResultsRecruitment was conducted between November 18 and December 11, 2020. The response rates in the 4 arms varied between 34.31% (2340/6821) and 41.17% (2043/4962). The prescreening classified 16.61% (1207/7266) of the patients as COVID-19 symptomatic. Altogether, 4232 persons without prescreening and 7623 participating in the prescreening provided 5351 gargle samples, of which 5319 (99.4%) could be analyzed. This yielded 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI 0.14%-0.59%) in the arms without prescreening and 0.05% (95% CI 0.00%-0.108%) in the arms with prescreening (initial contacts only). Specifically, we found a prevalence of 0.31% (95% CI 0.06%-0.58%) for individuals and 0.35% (95% CI 0.09%-0.61%) for households, and lower estimates with prescreening (0.07%, 95% CI 0.0%-0.15% for individuals and 0.02%, 95% CI 0.0%-0.06% for households). Asymptomatic infections occurred in 27% (3/11) of the positive cases with symptom data. The 2 arms without prescreening performed the best regarding effectiveness and accuracy. ConclusionsThis study showed that postal mailing of gargle sample kits and returning home-based self-collected liquid gargle samples followed by high-sensitivity RT-LAMP analysis is a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and integration into the public health system may increase the potential to monitor the course of the pandemic. Trial RegistrationDeutsches Register Klinischer Studien (DRKS) DRKS00023271; https://tinyurl.com/3xenz68a International Registered Report Identifier (IRRID)RR2-10.1186/s13063-021-05619-5

IntroductionBacterial plant diseases cause tremendous economic losses worldwide. However, a few effective and sustainable control methods are currently available. To discover novel and effective management approaches, we screened marine fungi for their antibacterial activity against phytopathogenic bacteria in vitro and in vivo.MethodsWe screened the culture broth of 55 fungal strains isolated from various marine sources (seawater, algae, and sediment) for their in vitro antibacterial activity using the broth microdilution method. Then, only the fungal strain (designated UL-Ce9) with higher antibacterial activity in vitro was tested in an in vivo experiment against tomato bacterial wilt. The active compounds of UL-Ce9 were extracted using ethyl acetate, purified by a series of chromatography, and the structure was elucidated by nuclear magnetic resonance spectroscopy. Pesticide formulations of toluquinol were prepared as soluble concentrates and wettable powder. The disease control efficacy of toluquinol formulations was evaluated against blight of rice and the bacterial wilt of tomato.Results and discussionThe culture broth of UL-Ce9 showed high antibacterial activity against Agrobacterium tumefaciens, Ralstonia solanacearum, and Xanthomonas arboricola pv. pruni in vitro, and we selected UL-Ce9 for the in vivo test. The UL-Ce9 culture broth completely suppressed the bacterial wilt of tomato at a dilution of 1:5. The phylogenetic analysis identified UL-Ce9 as Penicillium griseofulvum, and the antibacterial metabolites were revealed as patulin, gentisyl alcohol, and toluquinol, all of which were associated with the biosynthetic pathway of the mycotoxin patulin. Patulin exhibited the highest antibacterial activity against 16 phytopathogenic bacteria in vitro, followed by toluquinol and gentisyl alcohol. As patulin is toxic, we selected toluquinol to investigate its potential use as a pesticide against bacterial plant diseases. Compared with the chemicals currently being applied in agriculture (streptomycin and oxytetracycline), toluquinol formulations exhibited similar and higher control efficacies against bacterial leaf blight of rice and bacterial wilt of tomato, respectively. To the best of our knowledge, this is the first report of the antibacterial activity of toluquinol against phytopathogenic bacteria. Our results suggest that toluquinol is a potential candidate for the development of novel and effective pesticides for the management of bacterial plant diseases.

Abstract Background Economic growth is dependent on economic activity, which often translates to higher levels of carbon emissions. With the emergence of technologies that promote sustainable production, governments are working towards achieving their target economic growth while minimizing environmental emissions to meet their commitments to the international community. The IPCC reports that economic activities associated with electricity and heat production contributed most to GHG emissions and it led to the steady increase in global average temperatures. Currently, more than 90% of the total GHG emissions of the ASEAN region is attributable to Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. These regions are expected to be greatly affected with climate change. This work analyzes how ASEAN nations can achieve carbon reduction targets while aspiring for economic growth rates in consideration of interdependencies between nations. We thus develop a multi-regional input–output model which can either minimize collective or individual carbon emissions. A high-level eight-sector economy is used for analyzing different economic strategies. Results This model shows that minimizing collective carbon emissions can still yield economic growth. Countries can focus on developing sectors that have potentials for growth and lower carbon intensity as new technologies become available. In the case study examined, results indicate that the services sector, agriculture, and food manufacturing sector have higher potential for economic growth under carbon reduction emission constraints. In addition, the simultaneous implementation of multiple carbon emission reduction strategies provides the largest reduction in regional carbon emissions. Conclusions This model provides a more holistic view of how the generation of carbon emissions are influenced by the interdependence of nations. The emissions reduction achieved by each country varied depending on the state of technology and the level of economic development in the different regions. Though the presented case focused on the ASEAN region, the model framework can be used for the analysis of other multi-regional systems at various levels of resolution if data is available. Insights obtained from the model results can be used to help nations identify more appropriate and achievable carbon reduction targets and to develop coordinated and more customized policies to target priority sectors in a country. This model is currently limited by the assumption of fixed technical coefficients in the exchange and interdependence of different regions. Future work can investigate modelling flexible multi-regional trade where regions have the option of substituting goods and products in its import or export structure. Other strategies for reducing carbon emission intensity can also be explored, such as modelling transport mode choices, or establishing sectors for waste management. Hybrid models which integrate the multi-regional input–output linear program model with data envelopment analysis can also be developed.

Research aims: This study focuses on the correlation between public investment, current expenditure and payment for government debt, and economic growth in short-run and long-run estimations. Design/Methodology/Approach: Macro data of Vietnam in the period 1991-2020 were extracted from the World Bank and the Vietnam General Statistics Office. This research employed the Autoregressive Distributed Lag (ARDL) for time series. Research findings: The results of this study uncovered that an improvement in public investment could enhance economic growth; it is also true of the government’s current spending. However, it is worth noting that the coefficients of changes in public investment and government current spending reduced the economic growth change in one and two periods ago. Moreover, debt payment was found to have a negative effect on the economy at all lags with different levels of significance. Theoretical contribution/Originality: This study provides empirical evidence on the role of government spending in economic growth, thereby confirming that Keynesian theory still holds in the case of Vietnam. The study also verifies the vital role of government activity in regulating economic development through investment and expenditure. Practitioner/Policy implication: Some important implications for policymakers focusing on government spending are: (i) The government needs to have an investment strategy that focuses on the important areas, such as infrastructure and technology foundation. (ii) Government needs to improve accountability and transparency in the management. (iii) Supportive policies on capital, technology, human resources, and the market must be continued to encourage economic investment activities. (iv) The selection, evaluation, and approval of investment portfolios should be carefully and appropriately made. Research limitation: This study was limited by looking at the overview of government spending with economic growth, ignoring the spending structure due to the lack of necessary data. Therefore, the following studies need to clarify the spending structure of Vietnam to determine which expenditure types have negative/positive impacts on economic growth, thereby providing incentive solutions and necessary support from the government.

African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon the confirmation of the presence of the virus. Studies leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serially passaging a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophages (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 102 HAD50, to the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV in a dose range of 102 to 105 HAD50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was eliminated from blood by 28 days post-inoculation (DPI), and from feces or oral fluids by 17 DPI. Although the vaccine strain in serum remained a safe and attenuated phenotype after five passages in swine, a reversion-to-virulence study using blood or tissue homogenates at peak viremia will be conducted in the future. ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.

Abstract Background Antigen-based rapid diagnostic tests (Ag-RDT) have been implemented in hospitals and nursing homes to screen for infectious individuals without symptoms suggestive of SARS-CoV-2 infections and to prevent entry into these high-risk settings. Despite their benefits for screening, the cost of large-scale implementation is largely understudied. Our study presents evidence on their implementation costs in high-risk settings. This study aimed to estimate the economic costs of implementing Ag-RDT-based screening for SARS-CoV-2 in two tertiary care hospitals (University Hospital Heidelberg - UKHD, and Charité – Universitätsmedizin Berlin) and one nursing home in Germany. Methods We adopted a health system perspective and followed the three sequential steps to costing: identification of resources, measurement of resource consumption, and valuation of costs. Data on resource consumption were collected between October 2020 and April 2021 through various techniques and data sources. The cost estimation considered all costs along the screening algorithm including PCR confirmation tests for positive cases. We estimated the costs for the two implementation modalities observed: staff dedicated exclusively to screening and staff not dedicated exclusively to screening. Furthermore, cost estimations were performed under both observed capacity use and hypothetical capacity use assumptions (60, 80 and 100%). Results Our study indicates that the average cost per Ag-RDT is highly dependent on the capacity use and implementation mode. Staff time and test kits are the two main cost drivers of implementing the large-scale screening programs for SARS-CoV-2 using Ag-RDTs. For hospitals, the average cost per test in UKHD was €30.12 (capacity observed); €14.56 (non-dedicated mode); €19.47, €16.37, €14.53 at 60, 80, 100% capacity respectively (dedicated mode); and at Charité €13.10 (non-dedicated mode). For the nursing home the estimated average cost per test was €15.03 (non-dedicated mode). Conclusions The information on the estimated costs by mode of implementation and capacity use may support the planning of Ag-RDT-based covid-19 screening programs suitable for each institution. Further research is needed to cost this screening strategy for COVID-19 in other high-risk, high-income settings to reach generalizability.

Research aims: This study focuses on the correlation between tax revenue, investment, and economic growth, taking into account the non-linear effects of tax revenue. Design/Methodology/Approach: Macro data of nine countries in ASEAN (including Brunei, Cambodia, Indonesia, Laos, Malaysia, Philippines, Singapore, Thailand, and Vietnam) in 2000 - 2020 were extracted from the World Bank database. This research employed panel data estimations. Research findings: This study found statistical evidence of a negative effect of tax revenue on economic growth. However, when considering the non-linear effects of tax revenue, the empirical findings showed that higher tax revenue could reduce the disadvantages of tax impacts to boost economic growth. The negative effect of taxes is as obvious as the economic growth theories, but it depends on the taxation revenue. Lower tax revenue may encourage saving and investment, but it also leads to an increased government deficit, reducing economic growth through government debt, spending and investment. Moreover, this study provides consistent evidence of investment’s positive effect on economic growth in ASEAN countries during the research period. Theoretical contribution/Originality: The theoretical contribution provides evidence on the direct effect of tax revenue and investment on economic growth with a broader understanding of the tax’s non-linear effects and investment contributions in the ASEAN. The study confirms the vital role of government activity in regulating the development of the economy through taxation and investment. Practitioner/Policy implication: The severe impact of the COVID-19 pandemic has increased macroeconomic uncertainties, including uncertainty over savings, investment, and spending, potentially leading to tax revenue and investment losses. It, in turn, affects economic activities, so it requires careful consideration. Learned lessons from this study can prepare for future economic shocks and financial crises to reduce negative impacts on economic growth, including their adverse tax revenue effects. Research limitation: This study is limited by looking at the tax revenue ratio overview, which ignores the tax structure due to the lack of data collection. The following studies need to clarify the tax structure of ASEAN countries to determine which tax gives a negative impact/and which tax has a positive effect on economic growth.

Background and Aim: The selection and proper application of disinfectants are crucial to the prevention of many diseases, so disinfectants must be evaluated before being used for the prevention of African swine fever (ASF). Three disinfectant products belonging to the group of potassium hydrogen peroxymonosulfates, product A and product B, and a quaternary ammonium compound called product C, were examined in vitro for host cell cytotoxicity and the efficacy of ASF virus inactivation. The study parameters included various concentrations, exposure times, temperatures, and degrees of cytotoxicity. Materials and Methods: Three disinfectant products were evaluated for cytotoxicity using primary porcine alveolar macrophage (PAM) cells at dilutions from 1:200 to 1:51,200. Disinfectants in concentrations of 1:200, 1:400, and 1:800 were prepared, the pH and the virucidal activity were tested. An equal volume of each dilution was mixed with the ASF virus and incubated at room temperature (20°C) or on ice (4°C) for 1 min, 5 min, or 30 min. Hemadsorption (HAD) or rosette formation was observed using an inverted microscope for 5 days after inoculation, and the virus titer was calculated as HAD50/mL. Each treatment and virus control were tested in triplicate, and the titers were reported as means and standard deviations. The reduction factor was used to measure inactivation. Results: Products A, B, and C at 1:400, 1:800, and 1:25,600 of dilution, respectively, did not show significant cytotoxic effects on PAM cells. Products A and B could inactivate ASF virus at 1:200 dilution within 5 min after exposure at 4°C. However, at 20°C, the exposure time had to be extended to 30 min to inactivate the virus. Product C could inactivate the virus at 1:400 dilution within 5 min under both temperature conditions, whereas at 1:800 dilution, the exposure time had to be extended to 30 min to completely inactivate the virus at 20°C. Conclusion: All disinfectants could inactivate ASF virus in various concentrations, under appropriate exposure times and reaction temperatures, and there was no evidence of host cell cytotoxicity. For the control of ASF in pig farms, the appropriate concentration, ambient temperature, and contact time of these disinfectants should be taken into account.

Abstract Background To achieve higher effectiveness in population-based SARS-CoV-2 surveillance and to reliably predict the course of an outbreak, screening, and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. Methods This trial implements a two-factorial, randomized, controlled, multi-arm, prospective, interventional, single-blinded design with cluster sampling and four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy based on individuals’ self-collection of saliva samples which are then sent to and analyzed by a laboratory. The targeted sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (2500 participants per arm). Strategies differ with respect to tested population groups (individuals vs. all household members) and testing approach (without vs. with pre-screening survey). The trial is complemented by an economic evaluation and qualitative assessment of user experiences. Primary outcomes include costs per completely screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Discussion Systems for active surveillance of the general population will gain more importance in the context of pandemics and related disease prevention efforts. The pandemic parameters derived from such active surveillance with routine population monitoring therefore not only enable a prospective assessment of the short-term course of a pandemic, but also a more targeted and thus more effective use of local and short-term countermeasures. Trial registration ClinicalTrials.gov DRKS00023271 . Registered November 30, 2020, with the German Clinical Trials Register (Deutsches Register Klinischer Studien)

Background and Aim: African swine fever (ASF) is currently the most prevalent disease in swine. The disease is spreading throughout primary swine-producing countries with heavy losses in population and revenue. To date, no successful vaccines or medications have been reported. This study aimed to design and develop a blend of natural essential oils and test its efficacy against the ASF virus (ASFV) in swine. Materials and Methods: We attempted to develop a natural oil blend formulation (NOBF) and determine its efficacy against the ASFV. This study follows on from a previously published in vitro study that reported that the NOBF has anti ASFV properties. A study was designed using 21 healthy piglets of triple-cross (Landrace + Yorkshire + Durok) crossbred pathogen-free pigs with an average weight of 15 kg. The study consisted of NOBF-incubated, NOBF, positive control, and negative control groups. The NOBF groups were administered NOBF (80 mL/ton mixed in drinking water) beginning 10 days before the challenge and continuing throughout the experiment. The positive and negative control pigs consumed regular drinking water. The pigs were challenged by a sublethal dose of pure isolate ASFV strain Vietnam National University of Agriculture-ASFV-L01/HN/04/19 inoculation with 103.5 HAD50/dose through the intramuscular route. There were sic pigs in each group, three pigs directly IM challenged, and three pigs were considered cohoused pigs. Results: Both challenged (three) and cohoused (three) pigs in the positive control showed clinical signs of ASFV infection, as detected by real-time polymerase chain reaction (RT-PCR) in blood samples, oral swabs, and feces. There was 100% cumulative mortality, that is, both challenged and contact pigs died in the positive control group on day 20 of infection. No signs of infection or mortality were observed in the NOBF-incubated group. The challenged pigs in the NOBF-direct challenge group showed clinical signs and mortality, whereas no clinical signs or symptoms occurred in the cohoused pigs. The immunoglobulin G (IgG) level of the contact pigs was the highest in the treatment group and the lowest in the positive control group. The IgM level of the contact pigs in the treatment groups was the lowest, whereas that of the positive control was the highest. The RT-PCR test showed that the ASFV was deactivated in the NOBF-incubated group. The challenged and contact pigs of the positive control group had high Ct values. The challenged pigs of the NOBF group had high Ct values, whereas the contact pigs from the same group and those of the negative control were negative for the ASFV, determined by PCR, in all samples. The comparison of the challenged groups showed that the appearance of the virus was delayed by at least 2 days in the NOBF group compared to the positive control group. Conclusion: The results showed that NOBF can prevent the spread of the ASFV in a population. Moreover, NOBF can enhance the pig humoral immune system by enhancing IgG levels and reducing IgM levels. This study successfully demonstrated that NOBF is an anti-ASFV agent, which prevents horizontal transmission and enhances pig humoral immunity.

Background and Aim: African swine fever is one of the severe pathogens of swine. It has a significant impact on production and economics. So far, there are no known remedies, such as vaccines or drugs, reported working successfully. In the present study, the natural oil blend formulation's (NOBF) efficacy was evaluated against ASFV in vitro using porcine alveolar macrophages (PAMs) cells of swine. Materials and Methods: The capacity of NOBF against the ASFV was tested in vitro. The NOBF combines Eucalyptus globulus, Pinus sylvestris, and Lavandula latifolia. We used a 2-fold serial dilution to test the NOBF formulation dose, that is, 105 HAD50/mL, against purified lethal dose of African swine in primary PAMs cells of swine. The PAM cells survival, real-time polymerase chain reaction (PCR) test, and hemadsorption (HAD) observation were performed to check the NOBF efficacy against ASFV. Results: The in vitro trial results demonstrated that NOBF up to dilution 13 or 0.000625 mL deactivates the lethal dose 105 HAD50 of ASFV. There was no HAD (Rosetta formation) up to dilution 12 or 0.00125 mL of NOBF. The Ct value obtained by running real-time PCR of the NOBF group at 96 h post-infection was the same as the initial value or lower (25), whereas the Ct value of positive controls increased several folds (17.84). Conclusion: The in vitro trial demonstrated that NOBF could deactivate the ASFV. The NOBF has the potential to act as anti-ASFV agent in the field. The next step is to conduct in vivo level trial to determine its efficacy.

Abstract Objectives In this cluster-randomised controlled study (CoV-Surv Study), four different “active” SARS-CoV-2 testing strategies for general population surveillance are evaluated for their effectiveness in determining and predicting the prevalence of SARS-CoV-2 infections in a given population. In addition, the costs and cost-effectiveness of the four surveillance strategies will be assessed. Further, this trial is supplemented by a qualitative component to determine the acceptability of each strategy. Findings will inform the choice of the most effective, acceptable and affordable strategy for SARS-CoV-2 surveillance, with the most effective and cost-effective strategy becoming part of the local public health department’s current routine health surveillance activities. Investigating its everyday performance will allow us to examine the strategy’s applicability to real time prevalence prediction and the usefulness of the resulting information for local policy makers to implement countermeasures that effectively prevent future nationwide lockdowns. The authors would like to emphasize the importance and relevance of this study and its expected findings in the context of population-based disease surveillance, especially in respect to the current SARS-CoV-2 pandemic. In Germany, but also in many other countries, COVID-19 surveillance has so far largely relied on passive surveillance strategies that identify individuals with clinical symptoms, monitor those cases who then tested positive for the virus, followed by tracing of individuals in close contact to those positive cases. To achieve higher effectiveness in population surveillance and to reliably predict the course of an outbreak, screening and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. To better control and manage the SARS-CoV-2 pandemic, current strategies therefore need to be complemented by an active surveillance of the wider population, i.e. routinely conducted testing and monitoring activities to identify and isolate infected individuals regardless of their clinical symptoms. Such active surveillance strategies will enable more effective prevention of the spread of the virus as they can generate more precise population-based parameters during a pandemic. This essential information will be required in order to determine the best strategic and targeted short-term countermeasures to limit infection spread locally. Trial design This trial implements a cluster-randomised, two-factorial controlled, prospective, interventional, single-blinded design with four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy. Participants Eligible are individuals age 7 years or older living in Germany’s Rhein-Neckar Region who consent to provide a saliva sample (all four arms) after completion of a brief questionnaire (two arms only). For the qualitative component, different samples of study participants and non-participants (i.e. eligible for study, but refuse to participate) will be identified for additional interviews. For these interviews, only individuals age 18 years or older are eligible. Intervention and comparator Of the four surveillance strategies to be assessed and compared, Strategy A1 is considered the gold standard for prevalence estimation and used to determine bias in other arms. To determine the cost-effectiveness, each strategy is compared to status quo, defined as the currently practiced passive surveillance approach. Strategy A1: Individuals (one per household) receive information and study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the sample is tested for SARS-CoV-2 using Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP). Strategy A2: Individuals (one per household) receive information and study material by mail with instructions on how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. Strategy B1: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms and risk exposures. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the saliva sample is tested for SARS-CoV-2 using RT-LAMP. Strategy B2: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. In each strategy, RT-LAMP positive samples are additionally analyzed with qPCR in order to minimize the number of false positives. Main outcomes The identification of the one best strategy will be determined by a set of parameters. Primary outcomes include costs per correctly screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Secondary outcomes include participation rate, costs per asymptomatic case, prevalence estimates, number of asymptomatic cases per study arm, ratio of symptomatic to asymptomatic cases per study arm, participant satisfaction. Additional study components (not part of the trial) include cost effectiveness of each of the four surveillance strategies compared to passive monitoring (i.e. status quo), development of a prognostic model to predict hospital utilization caused by SARS-CoV-2, time from test shipment to test application and time from test shipment to test result, and perception and preferences of the persons to be tested with regard to test strategies. Randomisation Samples are drawn in three batches of three continuous weeks. Randomisation follows a two-stage process. First, a total of 220 sampling points have been allocated to the three different batches. To obtain an integer solution, the Cox-algorithm for controlled rounding has been used. Afterwards, sample points have been drawn separately per batch, following a probability proportional to size (PPS) random sample. Second, for each cluster the same number of residential addresses is randomly sampled from the municipal registries (self-weighted sample of individuals). The 28,125 addresses drawn per municipality are then randomly allocated to the four study arms A1, A2, B1, and B2 in the ratio 5 to 2.5 to 14 to 7 based on the expected response rates in each arm and the sensitivity and specificity of the pre-screening tool as applied in strategy B1 and B2. Based on the assumptions, this allocation should yield 2500 saliva samples in each strategy. Although a municipality can be sampled by multiple batches and the overall number of addresses per municipality might vary, the number of addresses contacted in each arm is kept constant. Blinding (masking) The design is single-blinded, meaning the staff conducting the SARS-CoV-2 tests are unaware of the study arm assignment of each single participant and test sample. Sample sizes Total sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (i.e. 2,500 participants per arm). For the qualitative component, up to 60 in-depth interviews will be conducted with about 30 study participants (up to 15 in each arm A and B) and 30 participation refusers (up to 15 in each arm A and B) purposefully selected from the quantitative study sample to represent a variety of gender and ages to explore experiences with admission or rejection of study participation. Up to 25 asymptomatic SARS-CoV-2 positive study participants will be purposefully selected to explore the way in which asymptomatic men and women diagnosed with SARS-CoV-2 give meaning to their diagnosis and to the dialectic between feeling concurrently healthy and yet also being at risk for transmitting COVID-19. In addition, 100 randomly selected study participants will be included to explore participants’ perspective on testing processes and implementation. Trial Status Final protocol version is “Surveillance_Studienprotokoll_03Nov2020_v1_2” from November 3, 2020. Recruitment started November 18, 2020 and is expected to end by or before December 31, 2020. Trial registration The trial is currently being registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00023271 ( https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00023271). Retrospectively registered 30 November 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Endoscopic retrograde cholangiopancreatography (ERCP) is a standard for diagnosing and treating hepato-pancreatico-biliary (HPB) diseases in clinical settings. ERCP-related complications are relatively common, ranging from 4 to 30%. The most common one is acute pancreatitis. ERCP-related necrotizing pancreatitis accounts for 7.7% of ERCP-related pancreatitis cases. This complication may still be misdiagnosed, which might lead to inappropriate treatment with a worse prognosis. Here, we report a 34-year-old case with ERCP-related necrotizing pancreatitis who was successfully managed, but initially misdiagnosed with biliary peritonitis.

Plant bacterial and fungal diseases cause significant agricultural losses and need to be controlled. Beneficial bacteria are promising candidates for controlling these diseases. In this study, Streptomyces sp. JCK-6131 exhibited broad-spectrum antagonistic activity against various phytopathogenic bacteria and fungi. In vitro assays showed that the fermentation filtrate of JCK-6131 inhibited the growth of bacteria and fungi with minimum concentration inhibitory (MIC) values of 0.31–10% and 0.31–1.25%, respectively. In the in vivo experiments, treatment with JCK-6131 effectively suppressed the development of apple fire blight, tomato bacterial wilt, and cucumber Fusarium wilt in a dose-dependent manner. RP-HPLC and ESI-MS/MS analyses indicated that JCK-6131 can produce several antimicrobial compounds, three of which were identified as streptothricin E acid, streptothricin D, and 12-carbamoyl streptothricin D. In addition, the disease control efficacy of the foliar application of JCK-6131 against tomato bacterial wilt was similar to that of the soil drench application, indicating that JCK-6131 could enhance defense resistance in plants. Molecular studies on tomato plants showed that JCK-6131 treatment induced the expression of the pathogenesis-related (PR) genes PR1, PR3, PR5, and PR12, suggesting the simultaneous activation of the salicylate (SA) and jasmonate (JA) signaling pathways. The transcription levels of PR genes increased earlier and were higher in treated plants than in untreated plants following Ralstonia solanacearum infection. These results indicate that Streptomyces sp. JCK-6131 can effectively control various plant bacterial and fungal diseases via two distinct mechanisms of antibiosis and induced resistance.

In recent years, the green synthesis of nanoparticles via biological processes has attracted considerable attention. Herein, we introduce a facile and green approach for the synthesis of poriferous silver nanoparticles (Ag-NPs) decorated hydroxylapatite (HAp@Ag) nanoparticles with excellent antibacterial properties. All the nanocomposites were fully characterized in the solid state via various techniques such as X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectrometer (EDX), in which the synthesized Ag-NPs (24 nm in diameter) and their homogeneous incorporation on HAp have been studied by ultraviolet-visible (UV-vis) technique, transmission electron microscopy (TEM), and dynamic light scattering (DLS) analysis. The obtained results indicate that the structure and morphology of HAp have no significant changes after the incorporation of Ag-NPs on its surface. Moreover, an impressive antibacterial activity of HAp@Ag nanocomposite against Gram-positive bacterium Staphylococcus aureus and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa has been recorded by using the agar well diffusion method. As a result, the HAp@Ag nanocomposite promises to be a great biomedical material with high antibacterial properties.

Abstract Background Bloodstream infections (BSIs) are associated with high morbidity and mortality worldwide. However their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. Systematic data from Vietnam are scarce. Here we present aetiologic data on BSI in adults admitted to a large tertiary referral hospital for infectious diseases in Hanoi, Vietnam. Methods A retrospective study was conducted at the National Hospital for Tropical Diseases between January 2011 and December 2013. Cases of BSI were determined from records in the microbiology department. Case records were obtained where possible and clinical findings, treatment and outcome were recorded. BSI were classified as community acquired if the blood sample was drawn ≤48 h after hospitalization or hospital acquired if >48 h. Results A total of 738 patients with BSI were included for microbiological analysis. The predominant pathogens were: Klebsiella pneumoniae (17.5%), Escherichia coli (17.3%), Staphylococcus aureus (14.9%), Stenotrophomonas maltophilia (9.6%) and Streptococcus suis (7.6%). The overall proportion of extended spectrum beta-lactamase (ESBL) production among Enterobacteriaceae was 25.1% (67/267 isolates) and of methicillin-resistance in S. aureus (MRSA) 37% (40/108). Clinical data was retrieved for 477 (64.6%) patients; median age was 48 years (IQR 36–60) with 27.7% female. The overall case fatality rate was 28.9% and the highest case fatality was associated with Enterobacteriaceae BSI (34.7%) which accounted for 61.6% of all BSI fatalities. Conclusions Enterobacteriaceae (predominantly K. pneumoniae and E. coli) are the most common cause of both community and hospital acquired bloodstream infections in a tertiary referral clinic in northern Vietnam.

Objective: The Knema genus contains various naturally occurring secondary metabolites with pharmacological potential, including antitumor, neuroprotective, antidiabetic, and hepatoprotective activities. This study focuses on identifying nitric oxide production inhibitors from Vietnamese Knema globularia. Methods: The secondary metabolites were isolated using several chromatographic techniques. Their chemical structures were determined using nuclear magnetic resonance (NMR) spectroscopy and compared with published literature. The anti-inflammatory effect was evaluated using the Griess assay, and protein interactions were investigated through docking studies. Results: Based on their anti-inflammatory activity, six compounds (1-6) were isolated from Vietnamese K. globularia. These compounds were identified as lupeol (1), formononetin (2), isoliquiritigenin (3), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]propane-1,3-diol (4), (+)-catechin (5), and (−)-epicatechin (6). For the first time, compounds 1, 3, and 4 were reported from Vietnamese K. globularia. All isolated compounds were tested against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells to assess their anti-inflammatory potential. Compound 5 exhibited the highest inhibitory activity, with an IC50 value of 5.61 μM, followed by compounds 3 and 6, with IC50 values of 6.76 and 11.52 μM, respectively. However, compounds 1, 2, and 4 showed inactivity with IC50 values exceeding 30 μM. Molecular docking was then employed to investigate the affinity and interactions between compounds 3, 5, and 6 and proteins involved in inflammation, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-8 (IL-8), along with ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions. Conclusion: These findings suggest that the active constituents derived from Vietnamese K. globularia have the potential as anti-inflammatory agents worthy of further exploration and development. [ABSTRACT FROM AUTHOR]

Introduction and aim. In real life, metastatic castration-resistant prostate cancer patients (mCRPC) had more complex clinical presentation than patients in the COU-AA-302 trial. This study primarily aimed to describe the overall survival of chemotherapy-naive mCRPC treated with abiraterone acetate plus prednisone (AAP). Other relevant outcomes and baseline characteristics of these patients were also evaluated. Material and methods. This retrospective, observational study collected data from chemotherapy-naive mCRPC patients treated with AAP in Vietnam. Kaplan-Meier curves were used to estimate time to treatment failure (TTF), and overall survival (OS). The impact of baseline characteristics on OS was explored using univariate and multivariate Cox proportional hazard models. Results. Data from 65 eligible patients were analyzed. The rate of PSA response was 73.8%, median PSA PFS was 10.5 months (95% CI: 7.4-13.6), median TTF was 15 months (95% CI: 11.1-18.9), and median OS was 24.9 months (95% CI: 18.9-30.9). Shorter OS was significantly associated with a higher Gleason score (≥8), shorter time from ADT start to mCRPC (<12 months), visceral metastases, and <50% PSA decline (p<0.05). Conclusion. Abiraterone acetate plus prednisone is well tolerated and effective for chemotherapy-naive mCRPC patients in clinical practice. Moreover, Gleason score, visceral metastasis, time from ADT start to mCRPC, and PSA response are the independent indicators for predicting the OS of mCRPC patients in both univariate and multivariate analyses. [ABSTRACT FROM AUTHOR]