Sensory, emotional, and appropriateness of plant- and meat-based burgers.

The plant-based meat alternative market is experiencing rapid growth. However, whether this growth extends to mainstream consumers will depend on the sensory profile, emotional profile, and situational appropriateness of these products. This study provides a sensory comparison between two plant-based burgers, one hybrid burger, and a conventional 100% ground beef burger. The sensory evaluation was carried out under blind and informed conditions using a between-subject design. Participants (n = 177) were asked to rate the appearance, flavor, odor, and texture of each product and indicate their overall liking. In addition, 26 sensory terms were evaluated using the rate-all-that-apply technique. The study also measured the emotional profile and the situational appropriateness elicited by each product using the check-all-that-apply technique. The results showed that (a) in the blind condition, there were no significant differences observed in overall liking across the four burgers; (b) the plant-based burger made with pea protein received the lowest overall liking score, and its evaluation was not positively influenced by product information disclosure; (c) providing product information influenced the perceived intensity of the attributes associated with meat; (d) discriminatory ability for emotions was higher in the informed condition; and (e) for the situational appropriateness, when prioritizing healthy eating, participants considered plant-based burgers more suitable than the groundbeef burger. PRACTICAL APPLICATION: Our results demonstrate that product descriptions could have an impact on consumer acceptance of different meat burger alternatives. In order to launch successfull meat alternatives, product developers and communication marketing specialists should consider the extent to which these alternatives resemble regular meat products in terms of their sensory and emotional profiles and context of use.

Sensory attributes of fine flavor cocoa beans and chocolate: A systematic literature review.

Fine flavor cocoa (FFC) is known for its unique flavor and aroma characteristics, which vary by region. However, a comprehensive overview of the common sensory attributes used to describe FFC beans and chocolate is lacking. Therefore, a systematic review was conducted to analyze existing literature and identify the most commonly used sensory attributes to describe FFC beans and chocolate. A systematic search of the Web of Science and Scopus databases was conducted in May 2023, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to ensure transparency and reproducibility. This review summarizes the origins of cocoa and explores their unique flavor profiles, encompassing caramel, fruity, floral, malty, nutty, and spicy notes. Although some origins may exhibit similar unique flavors, they are often described using more specific terms. Another main finding is that although differences in sensory attributes are anticipated at each production stage, discrepancies also arise between liquor and chocolate. Interestingly, fine chocolate as the final product does not consistently retain the distinctive flavors found in the liquor. These findings emphasize the need for precise descriptors in sensory evaluation to capture flavor profiles of each origin. As such, the exploration of attributes from bean to bar holds the potential to empower FFC farmers and chocolate producers to effectively maintain quality control.

Restrictive versus conventional ward fluid therapy in non-cardiac surgery patients and the effect on postoperative complications: a meta-analysis.

BACKGROUND: Diligent fluid management is an instrumental part of Enhanced Recovery After Surgery. However, the effect of a ward regimen to limit intravenous fluid administration on outcome remains unclear. We performed a meta-analysis investigating the effect of a restrictive versus a conventional fluid regimen on complications in patients after non-cardiac surgery in the postoperative period on the clinical ward. STUDY DESIGN: We performed a systematic search in MEDLINE, Embase, Cochrane Library, and CINAHL databases, from the start of indexing until June 2022, with constraints for English language and adult human study participants. Data were combined using classic methods of meta-analyses and were expressed as weighted pooled risk ratio (RR) or odds ratio (OR) with 95% confidence interval (CI). Quality assessment and risk of bias analyses was performed according to PRISMA guidelines. RESULTS: Seven records, three randomized controlled trials, and four non-randomized studies were included with a total of 883 patients. A restrictive fluid regimen was associated with a reduction in overall complication rate in the RCTs (RR 0.46, 95% CI 0.23 to 0.95; P < .03; I2 = 35%). This reduction in overall complication rate was not consistent in the non-randomized studies (RR 0.74, 95% CI 0.53 to 1.03; P 0.07; I2 = 45%). No significant association was found for mortality using a restrictive fluid regimen (RCTs OR 0.51, 95% CI 0.05 to 4.90; P = 0.56; I2 = 0%, non-randomized studies OR 0.30, 95% CI 0.06 to 1.46; P = 0.14; I2 = 0%). A restrictive fluid regimen is significantly associated with a reduction in postoperative length of stay in the non-randomized studies (MD - 1.81 days, 95% CI - 3.27 to - 0.35; P = 0.01; I2 = 0%) but not in the RCTs (MD 0.60 days, 95% CI - 0.75 to 1.95; P = 0.38). Risk of bias was moderate to high. Methodological quality was very low to moderate. CONCLUSION: This meta-analysis suggests restrictive fluid therapy on the ward may be associated with an effect on postoperative complication rate. However, the quality of evidence was moderate to low, the sample size was small, and the data came from both RCTs and non-randomized studies.

cCMP and cUMP phosphodiesterases in viral infections.

In bacteria, cCMP and cUMP have a key role in defense against infection with bacterial viruses. Bacteriophages encode phosphodiesterases (PDEs; 'nucleases'; Apyc1), which cleave cCMP/cUMP, counteracting this defense. We propose that PDEs are of broader biological relevance, including cCMP/cUMP-cleaving PDEs of eukaryotic viruses, which may constitute new drug targets.

European stakeholders' perspectives on implementation potential of precision weed control: the case of autonomous vehicles with laser treatment.

Weed control is a basic agricultural practice, typically achieved through herbicides and mechanical weeders. Because of the negative environmental impacts of these tools, alternative solutions are being developed and adopted worldwide. Following recent technical developments, an autonomous laser-based weeding system (ALWS) now offers a possible solution for sustainable weed control. However, beyond recent proof of performance, little is known about the adoption potential of such a system. This study assesses the adoption potential of ALWS, using a mixed-method approach. First, six macro-environmental factors regarding the adoption of ALWS were determined. This assessment is referred to as a Political, Economic, Social, Technological, Legal, Environmental (PESTLE) analysis and is conducted in a form of a literature review initiated by expert consultations. Second, a range of European stakeholders' perceptions of ALWS was evaluated in four focus-group discussions (n = 55), using a strengths, weaknesses, opportunities, threats (SWOT) analysis. The factors identified in the PESTLE and SWOT analyses were subsequently merged to provide a comprehensive overview of the adoption potential of ALWS. Labour reduction, precision treatment and environmental sustainability were found to be the most important advantages of ALWS. High costs and performance uncertainty were identified as the main weaknesses. To promote the adoption of ALWS, this study recommends the following: (1) Concrete performance results, both technical and economic, should be communicated to farmers. (2) Farmers' knowledge of precision agriculture should be improved. (3) Advantage should be taken of policies that are favourable towards non-chemical methods and the high demand for organic products. This article also extensively discusses regulatory barriers, the risks posed to the safety of both humans and the machines involved, technological challenges and requirements, and policy recommendations related to ALWS adoption.

Physico-Chemical Property, Sensory Profile and Consumer Acceptability of Water Buffalo (Bubalus bubalis L.) Chocolate Milk Using Alkalized and Natural Cocoa Powder.

Due to its nutritional quality and palatability, chocolate milk beverages are gaining popularity globally. Alkalized cocoa powder is mostly used in its production since it provides for more intense color and dispersibility, but it has a negative effect on the phytochemical content of cocoa powder. Studies have suggested that water buffalo milk is superior to other milk due to its higher protein content and superior emulsion properties. As such, this study investigated the physico-chemical characteristics, sensory profile, and consumer acceptability of commercial and prototype water buffalo chocolate milk incorporated with alkalized and natural cocoa powder. Based on four buffalo chocolate milk samples, consumer acceptance was assessed by 120 consumers, which was combined with descriptive sensory data using a trained panel (n = 8) to determine drivers of liking. Compositional proximate analysis of alkalized and natural cocoa powders showed a significant difference in pH, moisture content, ash content, and fat content. Descriptive analysis showed that 8 out of 13 attributes (color, visual sandiness, cocoa and vanilla aroma, smoothness, creaminess, vanilla taste, and chocolate aftertaste) were effective discriminators of sensory attributes. Overall, buffalo chocolate milk samples were equally liked, but hedonic ratings of the individual attributes revealed that the samples were statistically different for color, viscosity (mouthfeel), and chocolate flavor. Partial least square regression (PLSR) identified chocolate flavor, viscous appearance, viscous mouthfeel, and bitter aftertaste as positive "drivers of liking". The darker color provided by alkalized cocoa powder did not increase consumer liking. The purchase intention was equal for all chocolate milk samples, whether alkalized or natural. Both cocoa powders showed comparable performance in the manufacture of buffalo chocolate milk. Using natural cocoa powder may be beneficial to local producers of cocoa powder and cocoa farmers since it is easier to produce, while it can provide a marketing advantage for dairy beverages in the global trend of going back to "organic" and "natural".

A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication.

Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro, and had an IC50 of 18 µM for PLpro inhibition. Compound 1 also had low non-specific reactivity with thiols and reacted with glutathione 1-2 orders of magnitude slower than other commonly used electrophilic warheads. Finally, compound 1 had low toxicity in cells and mice and has a molecular weight of only 247 daltons and consequently has great potential for further optimization. Collectively, these results demonstrate that compound 1 is a promising lead fragment for future PLpro drug discovery campaigns.

Structure Elucidation and Biosynthesis of Nannosterols A and B, Myxobacterial Sterols from Nannocystis sp. MNa10993.

Myxobacteria represent an underinvestigated source of chemically diverse and biologically active secondary metabolites. Here, we report the discovery, isolation, structure elucidation, and biological evaluation of two new bacterial sterols, termed nannosterols A and B (1, 2), from the terrestrial myxobacterium Nannocystis sp. (MNa10993). Nannosterols feature a cholestanol core with numerous modifications including a secondary alcohol at position C-15, a terminal vicinal diol side chain at C-24-C-25 (1, 2), and a hydroxy group at the angular methyl group at C-18 (2), which is unprecedented for bacterial sterols. Another rare chemical feature of bacterial triterpenoids is a ketone group at position C-7, which is also displayed by 1 and 2. The combined exploration based on myxobacterial high-resolution secondary metabolome data and genomic in silico investigations exposed the nannosterols as frequently produced sterols within the myxobacterial suborder of Nannocystineae. The discovery of the nannosterols provides insights into the biosynthesis of these new myxobacterial sterols, with implications in understanding the evolution of sterol production by prokaryotes.

Microwave Roasting as an Alternative to Convection Roasting: Sensory Analysis and Physical Characterization of Dark Chocolate.

Roasting cocoa beans by means of microwave radiations seems to be a potential alternative to convection roasting, but little is known about the impact of this method on the perceived flavor profile of the chocolate. Therefore, this research focused on revealing the flavor perception of chocolate produced with microwave roasted cocoa beans assessed by both a trained panel and chocolate consumers. Samples of 70% dark chocolate produced from cocoa beans microwave roasted at 600 W for 35 min were compared with samples of 70% dark chocolate produced from cocoa beans convectively roasted at 130 °C for 30 min. Non-significant differences (p > 0.05) in the measured physical properties, such as color, hardness, melting, and flow behavior, showed that chocolate produced from microwave roasted cocoa beans can exhibit the same physical qualities as convection roasted chocolate. Moreover, combined discriminative triangle tests, with 27 judgements in total, performed by a trained panel, showed that each type of chocolate exhibited distinctive characteristics (d'-value = 1.62). Regarding the perceived flavor, "cocoa aroma" was cited as significantly higher for the chocolate produced from microwave roasted cocoa beans (n = 112) compared to chocolate produced from convection roasted cocoa beans (n = 100) by consumers. Both preference and willingness to buy were higher, though insignificant at a 5% level, for the microwave roasted chocolate. A final potential benefit (studied in this research) of microwave roasting cocoa beans is the reduced energy consumption, which was estimated at 75%. Taking all these results together, the microwave roasting of cocoa is shown to be a promising alternative to convection roasting.

Phage Therapy in Germany-Update 2023.

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany. They identified critical shortcomings including the lack of clinical trials, a paucity of appropriate regulation and a shortage of phages for clinical use. Phage therapy is currently being applied to a limited number of patients as individual treatment trials. There is presently only one site in Germany for large-scale good-manufacturing-practice (GMP) phage production, and one clinic carrying out permission-free production of medicinal products. Several phage banks exist, but due to varying institutional policies, exchange among them is limited. The number of phage research projects has remarkably increased in recent years, some of which are part of structured networks. There is a demand for the expansion of production capacities with defined quality standards, a structured registry of all treated patients and clear therapeutic guidelines. Furthermore, the medical field is still poorly informed about phage therapy. The current status of non-approval, however, may also be regarded as advantageous, as insufficiently restricted use of phage therapy without adequate scientific evidence for effectiveness and safety must be prevented. In close coordination with the regulatory authorities, it seems sensible to first allow some centers to treat patients following the Belgian model. There is an urgent need for targeted networking and funding, particularly of translational research, to help advance the clinical application of phages.

Recombinant Reporter Phage rTUN1::nLuc Enables Rapid Detection and Real-Time Antibiotic Susceptibility Testing of Klebsiella pneumoniae K64 Strains.

The emergence of multi-drug-resistant Klebsiella pneumoniae (Kp) strains constitutes an enormous threat to global health as multi-drug resistance-associated treatment failure causes high mortality rates in nosocomial infections. Rapid pathogen detection and antibiotic resistance screening are therefore crucial for successful therapy and thus patient survival. Reporter phage-based diagnostics offer a way to speed up pathogen identification and resistance testing as integration of reporter genes into highly specific phages allows real-time detection of phage replication and thus living host cells. Kp-specific phages use the host's capsule, a major virulence factor of Kp, as a receptor for adsorption. To date, 80 different Kp capsule types (K-serotypes) have been described with predominant capsule types varying between different countries and continents. Therefore, reporter phages need to be customized according to the locally prevailing variants. Recently, we described the autographivirus vB_KpP_TUN1 (TUN1), which specifically infects Kp K64 strains, the most predominant capsule type at the military hospital in Tunis (MHT) that is also associated with high mortality rates. In this work, we developed the highly specific recombinant reporter phage rTUN1::nLuc, which produces nanoluciferase (nLuc) upon host infection and thus enables rapid detection of Kp K64 cells in clinical matrices such as blood and urine. At the same time, rTUN1::nLuc allows for rapid antibiotic susceptibility testing and therefore identification of suitable antibiotic treatment in less than 3 h.

Clinical and virological features of first human monkeypox cases in Germany.

BACKGROUND: Monkeypox is a zoonotic orthopoxvirus infection endemic in central and western Africa. In May 2022, human monkeypox infections including human-to-human transmission were reported in a multi-country outbreak in Europe and North America. CASE PRESENTATIONS: Here we present the first two cases of monkeypox infection in humans diagnosed in Germany. We present clinical and virological findings, including the detection of monkeypox virus DNA in blood and semen. The clinical presentation and medical history of our patients suggest close physical contact during sexual interactions as the route of infection. CONCLUSION: Monkeypox requires rapid diagnosis and prompt public health response. The disease should be considered in the current situation especially the differential diagnosis of vesicular or pustular rash, particularly in patients with frequent sexual contacts. Most importantly, it is essential to raise awareness among all health professionals for the rapid and correct recognition and diagnosis of this disease, which is probably still underreported in Europe (Adler et al. in Lancet Infect Dis https://doi.org/10.1016/s1473-3099(22)00228-6 , 2022).

Emoji meanings (pleasure-arousal-dominance dimensions) in consumer research: Between-country and interpersonal differences.

In line with the increasing popularity of emoji, the need for methodological research into these pictorial representations of emotion remains. The present research contributes to this goal by continuing to establish the meaning of emoji and exploring these according to between-country and interpersonal differences. The emoji (n = 12) were selected to span the valence × arousal emotion space, and the PAD model (Pleasure-Arousal-Dominance) was used to establish emoji meaning for the three dimensions, operationalized as measurement on 6 × 3 semantic differentials. Participants in the main study came from three countries-Germany, Singapore, and Malaysia (n = 2465), and a supplementary study included the United Kingdom and New Zealand (n = 600) (subset of four emoji). The results confirmed that emoji meanings according to the PAD model were largely similar between countries (albeit not identical). There were multiple minor significant differences for individual emoji, and where these existed, they often related to the dimension of Arousal, prompting a need for further investigation. Interpersonal differences were examined for gender (men and women), age group (18-45 and 46-69 years old), and frequency of emoji use. Again, significant differences were smaller rather than larger and supported the notion that emoji are generally applicable for multicountry research. However, caution regarding the participants who use emoji infrequently may be warranted. PRACTICAL APPLICATION: The findings from this research will help academics and practitioners who are interested in using emoji for sensory and consumer research (or are already doing so) with more robust interpretations of their findings. For a set of 12 emoji that provide broad coverage of the valence × arousal emotional space, meanings are provided on the three dimensions of the PAD model. The data is collected in five countries and contributes to increased confidence that emoji meanings are by and large similar in these countries.

Frying dough with yellow mealworm oil: Aroma profile and consumer perception at a central location test and at home.

Insect oil is a valuable fraction that is obtained from insect processing. The aim of this study is to evaluate the impact of yellow mealworm oil (YMW) oil (crude, deodorized, and blended with vegetable oil) on the sensory evaluation and aroma profile of fried dough. The sensory evaluation was performed in a sensory lab (central location test, CLT) and at home in order to examine how the evaluation environment or context impacts consumer perceptions. The strongest liking and preference were found for the donuts that were fried in 100% deodorized YMW oil and in YMW oil blended with vegetable oil. The evaluation environment did not affect overall liking scores but had an impact on sensory profiling, with more discriminating sensory terms observed for the test that was conducted at the sensory lab than for the test that was conducted at home. A distinctive profile of volatile organic compounds (VOCs) was found for every fried dough. The discrimination between VOCs and other frying oils that were observed is well in line with the sensory descriptors and the consumer test results. Acetic acid, acetic acid ethenyl ester, and tetrahydro-6-propyl-2H-Pyran-2-one were present in the doughs that were fried in crude YMW oil and in its blend with vegetable oil. They were absent from deodorized YMW oil and from its blend with vegetable oil. This study shows that, as far as fried donuts are concerned, deodorized YMW oil is an alternative to a vegetable oil-the two lead to similar sensorial experiences and preferences. PRACTICAL APPLICATION: Yellow mealworm oil (YMW) oil is a co-product of insect protein that can be valorized in the food industry. In the present study, it is demonstrated that the deodorization of YMW oil produces positive sensorial experiences and increases consumer acceptance of insect-based food. Furthermore, findings indicate that consumer testing at home yields similar acceptance and preference ratings suggesting that this type of testing may be an alternative means of collecting reliable consumer data.

Feasibility to estimate mean systemic filling pressure with inspiratory holds at the bedside.

Background: A decade ago, it became possible to derive mean systemic filling pressure (MSFP) at the bedside using the inspiratory hold maneuver. MSFP has the potential to help guide hemodynamic care, but the estimation is not yet implemented in common clinical practice. In this study, we assessed the ability of MSFP, vascular compliance (Csys), and stressed volume (Vs) to track fluid boluses. Second, we assessed the feasibility of implementation of MSFP in the intensive care unit (ICU). Exploratory, a potential difference in MSFP response between colloids and crystalloids was assessed. Methods: This was a prospective cohort study in adult patients admitted to the ICU after cardiac surgery. The MSFP was determined using 3-4 inspiratory holds with incremental pressures (maximum 35 cm H2O) to construct a venous return curve. Two fluid boluses were administered: 100 and 500 ml, enabling to calculate Vs and Csys. Patients were randomized to crystalloid or colloid fluid administration. Trained ICU consultants acted as study supervisors, and protocol deviations were recorded. Results: A total of 20 patients completed the trial. MSFP was able to track the 500 ml bolus (p < 0.001). In 16 patients (80%), Vs and Csys could be determined. Vs had a median of 2029 ml (IQR 1605-3164), and Csys had a median of 73 ml mmHg-1 (IQR 56-133). A difference in response between crystalloids and colloids was present for the 100 ml fluid bolus (p = 0.019) and in a post hoc analysis, also for the 500 ml bolus (p = 0.010). Conclusion: MSFP can be measured at the bedside and provides insights into the hemodynamic status of a patient that are currently missing. The clinical feasibility of Vs and Csys was judged ambiguously based on the lack of required hemodynamic stability. Future studies should address the clinical obstacles found in this study, and less-invasive alternatives to determine MSFP should be further explored. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03139929.

Discovery, Biosynthesis and Biological Activity of a Succinylated Myxochelin from the Myxobacterial Strain MSr12020.

Myxobacteria feature unique biological characteristics, including their capability to glide on the surface, undergo different multicellular developmental stages and produce structurally unique natural products such as the catecholate-type siderophores myxochelins A and B. Herein, we report the isolation, structure elucidation and a proposed biosynthesis of the new congener myxochelin B-succinate from the terrestrial myxobacterial strain MSr12020, featuring a succinyl decoration at its primary amine group. Myxochelin-B-succinate exhibited antibacterial growth inhibition and moderate cytotoxic activity against selected human cancer cell lines. This unique chemical modification of myxochelin B might provide interesting insights for future microbiological studies to understand the biological function and biosynthesis of secondary metabolite succinylation.

Three New Stigmatellin Derivatives Reveal Biosynthetic Insights of Its Side Chain Decoration.

Myxobacteria generate natural products with unique chemical structures, which not only feature remarkable biological functions, but also demonstrate unprecedented biosynthetic assembly strategies. The stigmatellins have been previously described as potent inhibitors of the mitochondrial and photosynthetic respiratory chain and originate from an unusual polyketide synthase assembly line. While previous biosynthetic investigations were focused on the formation of the 5,7-dimethoxy-8-hydroxychromone ring, side chain decoration of the hydrophobic alkenyl chain in position 2 was investigated less thoroughly. We report here the full structure elucidation, as well as cytotoxic and antimicrobial activities of three new stigmatellins isolated from the myxobacterium Vitiosangium cumulatum MCy10943T with side chain decorations distinct from previously characterized members of this compound family. The hydrophobic alkenyl chain in position 2 of the herein described stigmatellins feature a terminal carboxylic acid group (1), a methoxy group at C-12' (2) or a vicinal diol (3). These findings provide further implications considering the side chain decoration of these aromatic myxobacterial polyketides and their underlying biosynthesis.

Cell-free production of personalized therapeutic phages targeting multidrug-resistant bacteria.

Bacteriophages are potent therapeutics against biohazardous bacteria, which rapidly develop multidrug resistance. However, routine administration of phage therapy is hampered by a lack of rapid production, safe bioengineering, and detailed characterization of phages. Thus, we demonstrate a comprehensive cell-free platform for personalized production, transient engineering, and proteomic characterization of a broad spectrum of phages. Using mass spectrometry, we validated hypothetical and non-structural proteins and could also monitor the protein expression during phage assembly. Notably, a few microliters of a one-pot reaction produced effective doses of phages against enteroaggregative Escherichia coli (EAEC), Yersinia pestis, and Klebsiella pneumoniae. By co-expressing suitable host factors, we could extend the range of cell-free production to phages targeting gram-positive bacteria. We further introduce a non-genomic phage engineering method, which adds functionalities for only one replication cycle. In summary, we expect this cell-free methodology to foster reverse and forward phage engineering and customized production of clinical-grade bacteriophages.

Prophylactic furosemide to prevent transfusion-associated circulatory overload: a randomized controlled study in rats.

Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion related morbidity and mortality. The only treatment is empirical use of furosemide. Our aim was to investigate if furosemide can prevent TACO. A randomized controlled trial was performed using a previously validated two-hit rat model for TACO. Volume incompliance was induced (first hit) in anemic, anesthetized Lewis rats. Rats were randomized to placebo, low-dose (5 mg kg-1) or high-dose (15 mg kg-1) furosemide-administered prior to transfusion (second-hit) and divided over two doses. Primary outcome was change in left-ventricular end-diastolic pressure (∆LVEDP) pre- compared to post-transfusion. Secondary outcomes included changes in preload, afterload, contractility and systemic vascular resistance, as well as pulmonary outcomes. Furosemide treated animals had a significantly lower ∆LVEDP compared to placebo (p = 0.041), a dose-response effect was observed. ∆LVEDP in placebo was median + 8.7 mmHg (IQR 5.9-11), + 3.9 (2.8-5.6) in the low-dose and 1.9 (- 0.6 to 5.6) in the high-dose group. The effect of furosemide became apparent after 15 min. While urine output was significantly higher in furosemide treated animals (p = 0.03), there were no significant changes in preload, afterload, contractility or systemic vascular resistance. Furosemide rapidly and dose-dependently decreases the rise in hydrostatic pulmonary pressure following transfusion, essential for preventing TACO.

Adolescent Substance Use Behavior Change Through School Intervention Is Improved by Teacher and School Implementation Support Together, Especially for Girls.

An earlier trial of a school-based, preventative intervention, HealthWise South Africa, demonstrated some efficacy in preventing adolescent drinking and smoking in the Western Cape, South Africa. This was followed by the current implementation trial, which examined how implementation support conditions influenced adolescent drinking and smoking behavior change in the HealthWise intervention. The hybridized implementation-effectiveness trial included 34 schools (n = 2175 students) that provided student data at four waves through Grades 8 to 10. Implementation support conditions included a combination of two components (enhanced school environment and teacher consultation), resulting in four conditions: enhanced school environment, teacher consultation, both components, and standard delivery. Using configural frequency analysis, we examined how drinking and smoking behavior change differed across four configurations of intervention support longitudinally and by gender. For baseline non-smokers, results indicated sustained differences in abstention from smoking and smoking initiation between schools that received both support components and schools in the standard delivery condition. These results were primarily driven by girls. For baseline drinkers and smokers in the both components condition, changes in drinking were delayed until Grade 9 and smoking decayed by Grade 10. Results suggest that providing both school and teacher implementation support synergistically facilitates improved intervention outcomes both immediately following intervention and 2 years later across schools with diverse resource levels. Future iterations of HealthWise, and other interventions, may benefit from a multilevel implementation support strategy to improve student outcomes. More research is needed to understand how to improve HealthWise effectiveness among boys.