Antibodies can prevent malaria by neutralizing the infectious Plasmodium falciparum sporozoites (SPZ) before they establish an infection in the liver. Circumsporozoite protein (CSP), the most ...abundant surface protein of SPZ is the leading candidate for passive (and subunit) immunization approaches against malaria. Comprehensive assessment of the parasite-inhibitory capacity of anti-CSP monoclonal antibodies (mAbs) is an important step in advancing CSP-based immunization strategies. In this study, we employed a quantitative imaging-based motility assay to quantify the effect of anti-CSP mAbs on SPZ motility, both in vitro and in human skin.Our assay provided a quantitative measure of mAb parasite-inhibitory capacity through measurement of the half-maximal motility inhibitory concentration (IC
) value for anti-CSP mAbs (IC
2A10: 24 nM, IC
3SP2: 71 nM). We found a sevenfold discrepancy between the IC
and the binding saturation concentration measured by ELISA, possibly related to the observed shedding of CSP-mAb complexes during SPZ movement. In a subset of SPZ (5%), in vitro motility was unaffected by the presence of 2A10 while 3SP2 was able to completely block movement. In our ex vivo skin explant model, SPZ proved less susceptible to anti-CSP mAbs compared to SPZ in an in vitro environment. By quantitatively assessing motility, we created a valuable tool that can be used for comprehensive assessment of anti-CSP mAb potency. Insight that will help deepen our understanding of anti-CSP mAb potency and guide selection of the most promising anti-CSP mAbs for downstream clinical development.
Malaria vaccine candidates based on live, attenuated sporozoites have led to high levels of protection. However, their efficacy critically depends on the sporozoites' ability to reach and infect the ...host liver. Administration via mosquito inoculation is by far the most potent method for inducing immunity but highly impractical. Here, we observed that intradermal syringe-injected
sporozoites (
SPZ) were 3-fold less efficient in migrating to and infecting mouse liver than mosquito-inoculated sporozoites (
SPZ). This was related to a clustered dermal distribution (2-fold-decreased median distance between
SPZ and
SPZ) and, more importantly, a 1.4-fold (significantly)-slower and more erratic movement pattern. These erratic movement patterns were likely caused by alteration of dermal tissue morphology (>15-μm intercellular gaps) due to injection of fluid and may critically decrease sporozoite infectivity. These results suggest that novel microvolume-based administration technologies hold promise for replicating the success of mosquito-inoculated live, attenuated sporozoite vaccines.
Malaria still causes a major burden on global health and the economy. The efficacy of live, attenuated malaria sporozoites as vaccine candidates critically depends on their ability to migrate to and infect the host liver. This work sheds light on the effect of different administration routes on sporozoite migration. We show that the delivery of sporozoites via mosquito inoculation is more efficient than syringe injection; however, this route of administration is highly impractical for vaccine purposes. Using confocal microscopy and automated imaging software, we demonstrate that syringe-injected sporozoites do cluster, move more slowly, and display more erratic movement due to alterations in tissue morphology. These findings indicate that microneedle-based engineering solutions hold promise for replicating the success of mosquito-inoculated live, attenuated sporozoite vaccines.
Diet has been associated with better mental health in general populations, but less is known on this association in patients with a history of coronary heart disease. The objective of this study is ...to examine the cross-sectional associations between dietary patterns and mental health in elderly patients with a history of myocardial infarction.
Data were drawn from the final assessment of the Alpha Omega cohort that monitored patients with a history of myocardial infarction (age range 60-80 years). 2171 patients with complete data for diet and mental health were included in this study. Diet was assessed with the 203-item Food Frequency Questionnaire, and subsequently categorized into two scores: the Dutch Healthy Nutrient and Food Score (DHNaFS) and the Dutch Undesirable Nutrient and Food Score (DUNaFS). Depressive symptoms, assessed with the Geriatric Depression Scale (GDS-15), and dispositional optimism, assessed with the 4-item questionnaire (4Q), were cross-sectionally analyzed in relation to dietary patterns using linear regression analysis.
Patients were on average 72.2 years old and 79.5% were male. The DHNaFS score was associated with less depressive symptoms and higher dispositional optimism (β = -0.108; P<0.001; and β = 0.074; P<0.001), whereas no associations were found with the DUNaFS score. Particularly, consumption of vegetables, fruits, whole grains, fish, and low fat-dairy were associated with less depressive symptoms and higher optimism. Similar associations were found when analyzing the association between average DHNaFS score over the preceding 41 months with depression β = -0.085; P<0.001) and higher dispositional optimism (β = 0.084; P<0.001).
A healthy dietary pattern, in particular a higher consumption of vegetables, fruit, whole grains, fish and low-fat dairy, was associated with less depressive symptoms and higher optimism. However, given the cross-sectional nature of our analyses, our findings may also be explained by more optimistic participants making healthier food choices. Therefore, future prospective or interventions studies are needed to establish the direction of causality of this association.
ClinicalTrials.gov NCT03192410.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phased microphone arrays have become a well-established tool for performing aeroacoustic measurements in wind tunnels (both open-jet and closed-section), flying aircraft, and engine test beds. This ...paper provides a review of the most well-known and state-of-the-art acoustic imaging methods and recommendations on when to use them. Several exemplary results showing the performance of most methods in aeroacoustic applications are included. This manuscript provides a general introduction to aeroacoustic measurements for non-experienced microphone-array users as well as a broad overview for general aeroacoustic experts.
Micro-algae are a new and promising source of nutrients. The main products obtainable are dried algae with high nutrients content and high-value compounds such as fatty acids, pigments and ...anti-oxidants. This paper analyses the market and the economic opportunities of micro-algae-based food and feed sectors in the EU through an integrated methodology composed by literature search, interviews to experts and Delphi survey. Results show that the quantities produced and the market size of nutrients obtained from micro-algae are still significantly smaller in comparison to the ones derived from cereals and other commodity crops, but that the sector has seen an impressive and unique growth. Despite the challenges due to the climatic conditions together with the insufficient domestic demand and the complexity of the EU Novel Food regulation, the survey revealed that the EU can improve its market position in the next decade, thanks to its scientific and technological capacity and its dominant position in the global agri-food markets. New micro-algae-based products can be developed for foreign markets, and the improved global production share of European firms (presently of about 5%) may be the result of strategic acquisitions of foreign companies.
•Micro-algae are considered an alternative source of high-value nutrients.•Their production is not yet able to contribute to food security but is growing.•Production in the EU is limited due to climatic, economic and regulatory issues.•The EU can nonetheless become market leader in the next decade.•The EU's strengths are its technological capacity and the agri-food markets.
Purpose
The COVID-19 pandemic had a major impact on the health services worldwide. We aimed to investigate the impact of the pandemic on colorectal cancer (CRC) care in the Netherlands in 2020.
...Methods
CRC patients, diagnosed in 2018–2020 in the Netherlands, were selected from the Netherlands Cancer Registry (NCR). The year 2020 was divided in four periods reflecting COVID-19 developments in the Netherlands (pre-COVID, 1st peak, recovery period, 2nd peak) and compared with the same periods in 2018/2019. Patient characteristics and treatment were compared using the Chi-squared test. Median time between diagnosis and treatment, and between (neo)adjuvant therapy and surgery were analyzed by the Mann–Whitney
U
test.
Results
In total, 38,021 CRC patients were diagnosed in 2018/2019 (
n
= 26,816) and 2020 (
n
= 11,205). Median time between diagnosis and initial treatment decreased on average 4 days and median time between neoadjuvant radiotherapy and surgery in clinical stage II or III rectal cancer patients increased on average 34 days during the three COVID-19 periods compared to the same periods of 2018/2019. The proportion of colon cancer patients that underwent elective surgery significantly decreased with 3.0% during the 1st peak. No differences were found in the proportion of patients who received (neo)adjuvant therapy, systemic therapy, or no anti-cancer treatment.
Conclusion
Only minor changes in the care for CRC patients occurred during the COVID-19 pandemic, mostly during the 1
st
peak. In conclusion, the impact on CRC care in the Netherlands was found to be limited. However, long-term effects cannot be precluded.
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•Soluble proteins from the green alga Tetraselmis suecica were extracted.•The extraction process was mild and simple (one step), requiring low energy input.•Protein enrichment was ...achieved by controlling the bead milling time.•The crude protein extract showed excellent surface activity and gelation behaviour.•The functionality of the alga extract was superior to whey protein isolates.
The use of a single controlled bead milling step of the microalga Tetraselmis suecica resulted in a soluble fraction, rich in functional proteins. This was achieved by fine-tuning the processing time, thereby exploiting the difference in rates of protein and carbohydrate release during milling. Soluble proteins were extracted under mild conditions -room temperature, no addition of chemicals, pH 6.5-, with a yield of 22.5% and a specific energy consumption of 0.6 kWh kgDW−1, which is within the recommended minimum energy for an extraction step in a biorefinery process. The resulting protein extract contained 50.4% (DW) of proteins and 26.4% carbohydrates, showed light green color and displayed superior surface activity and gelation behavior compared to whey protein isolate. The proposed process is simple (only one bead milling step), scalable, and allows the mild extraction of functional proteins, making it interesting for industrial applications in the food industry.
Conservation initiatives are failing to arrest the global loss of biodiversity. From our mechanistic studies of ecology and economics, we suggest that for grazing lands the root cause of this failure ...is a powerful economic deterrent to measures designed to protect diversity. We identify an exponential relationship between monetary returns and intensification of farming methods over an extremely wide range of grassland productivities and farm systems. At intermediate to high levels of fertility, however, this exponential increase in financial benefit from intensification is associated with a decline in biodiversity and an acceleration of the ecological processes driving species losses from grassland ecosystems.
Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard ...combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH.
In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability.
Seventy patients (mean 57.9 years SD 14.0; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018).
In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF.
This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis.
#NCT02900443.
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•Limited efficacy and tolerability of standard prednisolone and azathioprine combination therapy in autoimmune hepatitis.•Mycophenolate mofetil combined with prednisolone is effective as first-line therapy for achieving biochemical remission.•Mycophenolate mofetil has a more favourable tolerability profile than azathioprine.
•A 100g.L−1 slurry of Nannochloropsis gaditana was submitted to cell disruption.•Multiple cell disruption methods were screened on the slurry.•High-pressure homogenization and bead milling were the ...most efficient.•Pulsed Electric Field was the least efficient on all levels.•The lowest energy cost per unit of released protein was obtained with HPH.•The mathematical model corresponds to the experimental data of HPH and bead milling.
Several cell disruption methods were tested on Nannochloropsis gaditana, to evaluate their efficiency in terms of cell disintegration, energy input and release of soluble proteins. High-pressure homogenization (HPH) and bead milling were the most efficient with >95% cell disintegration, ±50% (w/w) release of total proteins and low energy input (<0.5kWh.kg−1biomass). Enzymatic treatment required low energy input (<0.34kWh.kg−1biomass), but it only released ±35% protein (w/w). Pulsed Electric Field (PEF) was neither energy-efficient (10.44kWh.kg−1biomass) nor successful for protein release (only 10% proteins w/w) and cell disintegration. The release of proteins after applying HPH and bead milling always required less intensive operating conditions for cell disruption. The energy cost per unit of released protein ranged from 0.15–0.25 €.kgProtein−1 in case of HPH, and up to 2–20 €.kgProtein−1 in case of PEF.
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