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Abstract The research investigates the potential use of maize cobs (or corncobs) from five genotypes, including the B73 inbred line and four locally cultivated landraces from Northern Italy, as substrate for implementing Solid State fermentation processes with four Medicinal Mushrooms (MMs). The corncobs were characterized based on their proximate composition, lignin, phenolics content (both free and bound), and total antioxidant capacity. Among the MMs tested, Pleurotus ostreatus and Ganoderma annularis demonstrated the most robust performance. Their growth was parametrized using Image Analysis technique, and chemical composition of culture samples was characterized compared to that of corncobs alone. In all culture samples, the growth of MMs led to a significant reduction (averaging 40%) in the total phenolics contents compared to that measured in corncobs alone. However, the high content of free phenolics in the cobs negatively impacted the growth of P. ostreatus. The final MM-corncob matrix exhibited reduced levels of free sugars and starch (≤ 2.2% DW, as a sum) and increased levels of proteins (up to 5.9% DW) and soluble dietary fiber (up to 5.0% DW), with a notable trend toward higher levels of β-glucan compared to corncobs alone. This research paves the way for the use of this matrix as an active ingredient to enhance the nutritional value of food preparations.

Abstract Background People with depression often present with concurrent cognitive impairment. Computerized cognitive training (CCT) is a safe and efficacious strategy to maintain or enhance cognitive performance in a range of clinical populations. However, its efficacy in people with depression and how it varies across populations and design factors are currently unclear. Methods We searched MEDLINE, EMBASE, and PsycINFO from inception to 13 July 2021 for randomised controlled trials examining the efficacy of CCT vs any control condition on cognitive, mood, psychiatric symptoms, psychosocial, and daily functioning in adults with depression. Eligible samples include studies specifically targeting people with major depressive disorder as well as those with other diagnoses where at least 50% of the sample meets the clinical criteria for depression, with the exception of major psychiatric disorders or dementia. The primary outcome is change in the overall cognitive performance. Multivariate analyses will be used to examine the effect sizes on each outcome category as well as possible effect modifiers and correlations between categories. The risk of bias will be assessed using the Cochrane risk of bias tool version 2. Discussion To the best of our knowledge, this will be the first systematic review and meta-analysis of narrowly defined CCT across clinical populations with depression. We aim to investigate not only whether CCT is efficacious for cognition, but also how such effects vary across design factors, what other clinically relevant outcomes might respond to CCT, and the extent to which they differ across populations. Systematic review registration PROSPERO CRD42020204209

Arcobacter spp. is an emerging pathogen that is increasingly recognized as a cause of human infections. Gastrointestinal manifestations are most described in the case report literature. We present a case of the first documented case of Arcobacter spp. isolated in pericardial fluid in an immunocompromised patient with worsening cardiac tamponade that was successfully managed with an urgent pericardiocentesis and ensuing steroids, antibiotics, and a pericardial drain. The patient had a past medical history of HIV, latent syphilis, PCP pneumonia, ESRD, and hypertension, and presented with worsening dyspnea, subjective fever, myalgias, cough, pleuritic chest pain, and pericardial rub. Diagnostic workup revealed a positive COVID-19 PCR test, elevated high-sensitive cardiac troponins, elevated CRP, elevated D-dimer, and elevated creatinine. An ECG revealed diffuse ST-segment elevation, and imaging showed cardiomegaly with pulmonary vascular congestion and diffuse interstitial edema. Urgent TTE showed a large circumferential pericardial effusion with tamponade physiology present. Culture on aerobic blood agar grew Arcobacter spp. of unknown specific species, and blood cultures were also positive for Arcobacter spp. Treatment involved intravenous meropenem for five days, followed by oral ciprofloxacin, low-dose colchicine, and a tapered dose of ibuprofen. Repeat laboratory data and TTE showed complete resolution of the pericardial effusion and improved left ventricular function. This case highlights the potential for Arcobacter spp. to cause severe infections and the importance of considering it as a possible pathogen in patients with atypical presentations.

Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y 12 signaling (VerifyNow P2Y 12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y 12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0–167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y 12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583) [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Applying a circular economy approach, this research explores the use of cheese whey permeate (CWP), by-product of whey ultrafiltration, as cheap substrate for the production of bacterial cellulose (BC) and Sakacin-A, to be used in an antimicrobial packaging material. BC from the acetic acid bacterium Komagataeibacter xylinus was boosted up to 6.77 g/L by supplementing CWP with β-galactosidase. BC was then reduced to nanocrystals (BCNCs, 70% conversion yield), which were then conjugated with Sakacin-A, an anti-Listeria bacteriocin produced by Lactobacillus sakei in a CWP based broth. Active conjugates (75 Activity Units (AU)/mg), an innovative solution for bacteriocin delivery, were then included in a coating mixture applied onto paper sheets at 25 AU/cm2. The obtained antimicrobial food package was found effective in reducing Listeria population in storage trials carried out on a fresh Italian soft cheese (named “stracchino”) intentionally inoculated with Listeria. Production costs of the active material have been mainly found to be associated (90%) to the purification steps. Setting a maximum prudential 50% cost reduction during process up-scaling, conjugates coating formulation would cost around 0.89 €/A4 sheet. Results represent a practical example of a circular economy production procedure by using a food industry by-product to produce antimicrobials for food preservation.

Two Zymomonas mobilis wild strains (UMB478 and 479) isolated from water kefir were characterized for their biomass production levels and leavening performance when used as the inoculum of a real bread-like dough formulation. The obtained baked product would be consumable by people with adverse responses to Saccharomyces cerevisiae. In liquid cultures, the two strains reached similar biomass concentration (0.7 g CDW/L). UMB479 showed an interesting resistance to NaCl (MBC 30 g/L), that may be useful in the bakery sector. When inoculated in doughs, UMB479 produced the maximum dough volume (650 mL) after 5 h, glucose was almost consumed and 1 g/100 g of ethanol produced, +200% respective to UMB478. Using S. cerevisiae for comparison purposes, the dough doubled its volume fast, in only 2 h, but reached a final level of 575 mL, lower than that achieved by Z. mobilis. The analysis of bacterial and fungal population dynamics during dough leavening was performed through the Automated Ribosomal Intergenic Spacer Analysis (ARISA); doughs leavened by UMB479 showed an interesting decrease in fungal richness after leavening. S. cerevisiae, instead, created a more complex fungal community, similar before and after leavening. Results will pave the way for the use of Z. mobilis UMB479 in commercial yeast-free leavened products.

Introduction Current dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners.Research design and methods This was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7–14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion.Results D-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002).Conclusions This is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose.Trial registration number NCT02714413.

Summary: Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown. In this prospective PD investigation, vorapaxar was associated with reduced platelet-mediated thrombogenicity without affecting clot kinetics irrespective of DM status. However, platelet-mediated thrombogenicity increased after aspirin withdrawal, particularly among patients with DM. (Optimizing anti-Platelet Therapy In diabetes MellitUS-5 Study [OPTIMUS-5]; NCT02548650) Key Words: dual antiplatelet therapy, pharmacodynamics, platelets, thrombin, vorapaxar

The treatability of seven wastewater samples generated by a textile digital printing industry was evaluated by employing 1) anammox-based processes for nitrogen removal 2) microalgae (Chlorella vulgaris) for nutrient uptake and biomass production 3) white-rot fungi (Pleurotus ostreatus and Phanerochaete chrysosporium) for decolorization and laccase activity. The biodegradative potential of each type of organism was determined in batch tests and correlated with the main characteristics of the textile wastewaters through statistical analyses. The maximum specific anammox activity ranged between 0.1 and 0.2 g N g VSS-1 d-1 depending on the sample of wastewater; the photosynthetic efficiency of the microalgae decreased up to 50% during the first 24 hours of contact with the textile wastewaters, but it improved from then on; Pleurotus ostreatus synthetized laccases and removed between 20-62% of the colour after 14 days, while the enzymatic activity of Phanerochaete chrysosporium was inhibited. Overall, the findings suggest that all microbes have great potential for the treatment and valorisation of textile wastewater after tailored adaptation phases. Yet, the depurative efficiency can be probably enhanced by combining the different processes in sequence.

Background Vorapaxar as an adjunct to dual antiplatelet therapy (DAPT) reduces thrombotic events in patients with prior myocardial infarction at the expense of increased bleeding. Withdrawal of aspirin has emerged as a bleeding reduction strategy. The pharmacodynamic effects of vorapaxar with potent P2Y12 inhibitors as well as the impact of dropping aspirin is unexplored and represented the aim of the VORA‐PRATIC (Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y12 Receptor Inhibitors Prasugrel and Ticagrelor) study. Methods and Results Post–myocardial infarction patients (n=130) on standard DAPT (aspirin+prasugrel or ticagrelor) were randomized to 1 of 3 arms: (1) triple therapy: aspirin+prasugrel/ticagrelor+vorapaxar; (2) dual therapy (drop aspirin): prasugrel/ticagrelor+vorapaxar; (3) DAPT: aspirin+prasugrel/ticagrelor. Pharmacodynamic assessments were performed at 3 time points (baseline and 7 and 30 days). Vorapaxar reduced CAT (collagen‐ADP‐TRAP)–induced platelet aggregation, a marker of platelet‐mediated global thrombogenicity (triple therapy versus DAPT at 30 days: mean difference=–27; 95% CI,–35 to –19; P

Abstract Background The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI). Following clinical implementation of CYP2C19 genotyping at University Florida (UF) Health Shands Hospital in 2012, where genotype results are available approximately 3 days after PCI, testing was expanded to UF Health Jacksonville in 2016 utilizing a rapid genotyping approach. We describe metrics with this latter implementation. Methods Patients at UF Health Jacksonville undergoing left heart catheterization with intent to undergo PCI were targeted for genotyping using the Spartan RX™ system. Testing metrics and provider acceptance of testing and response to genotype results were examined, as was antiplatelet therapy over the 6 months following genotyping. Results In the first year, 931 patients, including 392/505 (78%) total patients undergoing PCI, were genotyped. The median genotype test turnaround time was 96 min. Genotype results were available for 388 (99%) PCI patients prior to discharge. Of 336 genotyped PCI patients alive at discharge and not enrolled in an antiplatelet therapy trial, 1/6 (17%) poor metabolizers (PMs, with two nonfunctional alleles), 38/93 (41%) intermediate metabolizers (IMs, with one nonfunctional allele), and 119/237 (50%) patients without a nonfunctional allele were prescribed clopidogrel (p = 0.110). Clopidogrel use was higher among non-ACS versus ACS patients (78.6% vs. 42.2%, p

The lace plant (Aponogeton madagascariensis) is an aquatic monocot that utilizes programmed cell death (PCD) to form perforations throughout its mature leaves as part of normal development. The lace plant is an emerging model system representing a unique form of developmental PCD. The role of autophagy in lace plant PCD was investigated using live cell imaging, transmission electron microscopy (TEM), immunolocalization, and in vivo pharmacological experimentation. ATG8 immunostaining and acridine orange staining revealed that autophagy occurs in both healthy and dying cells. Autophagosome-like vesicles were also found in healthy and dying cells through ultrastructural analysis with TEM. Following autophagy modulation, there was a noticeable increase in vesicles and vacuolar aggregates. A novel cell death assay utilizing lace plant leaves revealed that autophagy enhancement with rapamycin significantly decreased cell death rates compared to the control, whereas inhibition of autophagosome formation with wortmannin or blocking the degradation of cargoes with concanamycin A had an opposite effect. Although autophagy modulation significantly affected cell death rates in cells that are destined to die, neither the promotion nor inhibition of autophagy in whole plants had a significant effect on the number of perforations formed in lace plant leaves. Our data indicate that autophagy predominantly contributes to cell survival, and we found no clear evidence for its direct involvement in the induction of developmental PCD during perforation formation in lace plant leaves.

First isolated in 1943, Stenotrophomonas maltophilia (S. maltophilia) has historically been of little significance as it was considered a pathogen of low virulence noted to rarely infect immunocompromised hosts. However, over the last 30 years the prevalence of infection caused by the organism has increased significantly. Bacterial endocarditis from S. maltophilia remains exceedingly rare with only a small number of reported cases in the literature. This case involves a 27 year old male with sickle cell anemia with an indwelling right subclavian port who presented to the emergency department with myalgias, fever, and chills. His initial blood cultures grew Gram negative rods later identified as S. maltophilia. Transthoracic echocardiogram showed a mass in the right atrium. Transesophageal echocardiogram revealed a large C-shaped mass with attachment to the tricuspid annulus, mitral valve wall, and port tip in right atrium. The patient underwent sternotomy with removal of the vegetation to prevent embolization. He was treated with intravenous ciprofloxacin and oral trimethoprim/sulfamethoxazole to complete a full 6 weeks of therapy, making a full recovery. This report will further explore the unique presentation of this pathogen along with its epidemiology, resistance mechanisms, risk factors for infection, diagnosis, and appropriate antimicrobial treatment. Keywords: S. Maltophilia, Endocarditis

The present research investigates the effect of different pretreatments on glucose and fructose consumption and ethanol production by four Saccharomyces cerevisiae wine strains, three isolated and identified from different wine regions in Turkey and one reference strain. A mild stress temperature (45 °C, 1 h) and the presence of ethanol (14% v/v) were selected as pretreatments applied to cell cultures prior to the fermentation step in synthetic must. The goodness fit of the mathematical models was estimated: linear, exponential decay function and sigmoidal model were evaluated with the model parameters R2 (regression coefficient), RMSE (root mean square error), MBE (mean bias error) and χ2 (reduced Chi-square). Sigmoidal function was determined as the most suitable model with the highest R2 and lower RMSE values. Temperature pretreatment allowed for an increase in fructose consumption rate by two strains, evidenced by a t90 value 10% lower than the control. One of the indigenous strains showed particular promise for mild temperature treatment (45 °C, 1 h) prior to the fermentation step to reduce residual glucose and fructose in wine. The described procedure may be effective for indigenous yeasts in preventing undesirable sweetness in wines.

A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y 12 inhibition with cangrelor to oral P2Y 12 inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI). This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients. SWAP-6 (Switching Antiplatelet-6) was a prospective, randomized, 3-arm, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study. Patients (N = 77) were randomized to 1) prasugrel only at the start of PCI, 2) cangrelor plus prasugrel concomitantly at the start of PCI, or 3) cangrelor at the start of PCI plus prasugrel at the end of infusion. Cangrelor infusion was maintained for 2 hours. PK/PD assessments were performed at baseline and 6 time points postrandomization. The primary endpoint was noninferiority in VerifyNow (Werfen) P2Y 12 reaction units measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered vs prasugrel only. PK assessments included plasma levels of the active metabolite of prasugrel. Compared with prasugrel, cangrelor further enhances P2Y 12 inhibitory effects. At 4 hours postrandomization, P2Y 12 reaction unit levels were significantly lower with prasugrel only compared to cangrelor and prasugrel concomitantly administered (least squares means difference = 130; 95% CI: 85-176), failing to meet the prespecified noninferiority margin. Findings were corroborated by multiple PD assays. The active metabolite of prasugrel levels were not affected by concomitant administration of cangrelor and were low at the end of cangrelor infusion. In patients undergoing PCI, concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a DDI. (Switching Antiplatelet Therapy-6 [SWAP-6]; NCT04668144) [Display omitted] [ABSTRACT FROM AUTHOR]

This research focuses on the leavening performances and development of volatile compounds of three strains of Zymomonas mobilis in the production of yeast-free doughs. Z. mobilis DSM 3580, 424, and 473 were used in doughs supplemented with glucose and with or without NaCl. Z. mobilis produced about 10 mg ethanol/g dough, with maximum dough volumes (640–680 mL) being reached after 2 h leavening. NaCl addition postponed this parameter up to 6 h. Among organic acids, hexanoic acid resulted the highest produced compound; DSM 424 and 473 formed more propanoic, butanoic and pentanoic acid, being both negatively affected by NaCl. Esters were mainly discriminated on NaCl addition, with octanoic acid (DSM 3580), butanoic acid (DSM 424), and propanoic acid (DSM 473) ethyl esters as main components. DSM 3580 specifically produced 2-heptanal, DSM 424 2-hexadecenal, (E) and DSM 473 octanal, while DSM 424 and DSM 473 produced 2-butanone-4-hydroxy better than DSM 3580. Z. mobilis unique signatures were the production of nonanoic and undecanoic acids, 2-hexadecenal, (E), L(+)-tartaric acid diethyl ester and 3-decen-5-one, 4-methyl, (E). This outcome can pave the way for using Z. mobilis in baking goods, providing innovation possibilities in the area of yeast-free leavened products.

Cheese Whey Permeate (CWP) is the by-product of whey ultrafiltration for protein recovery. It is highly perishable with substantial disposal costs and has serious environmental impact. The aim of the present study was to develop a novel and cheap CWP-based culture medium for Lactobacillus sakei to produce the food-grade sakacin A, a bacteriocin exhibiting a specific antilisterial activity. Growth conditions, nutrient supplementation and bacteriocin yield were optimized through an experimental design in which the standard medium de Man, Rogosa and Sharpe (MRS) was taken as benchmark. The most convenient formulation was liquid CWP supplemented with meat extract (4 g/L) and yeast extract (8 g/L). Although, arginine (0.5 g/L) among free amino acids was depleted in all conditions, its supplementation did not increase process yield. The results demonstrate the feasibility of producing sakacin A from CWP. Cost of the novel medium was 1.53 €/L and that of obtaining sakacin A 5.67 €/106 AU, with a significant 70% reduction compared to the corresponding costs with MRS (5.40 €/L, 18.00 €/106 AU). Taking into account that the limited use of bacteriocins for food application is mainly due to the high production cost, the obtained reduction may contribute to widening the range of applications of sakacin A as antilisterial agent.

Zymomonas mobilis, because of its fermentative metabolism, has potential food applications in the development of leavened baked goods consumable by people with adverse responses to Saccharomyces cerevisiae. Since Z. mobilis is not able to utilize maltose present in flour, the effect of sucrose addition (2.5 g/100 g flour) on bread dough leavening properties was studied. For comparison purposes, leavening performances of S. cerevisiae with and without sucrose were also investigated. Doughs leavened by Z. mobilis without sucrose addition showed the lowest height development (14.95 ± 0.21 mm) and CO2 production (855 ± 136 mL). When sucrose was added, fermentative performances of Z. mobilis significantly (p < 0.05) improved (+80% and +85% of gas production and retention, respectively), with a dough maximum height 2.6 times higher, results indicating that Z. mobilis with sucrose can be leavened in shorter time with respect to the sample without addition. S. cerevisiae did not benefit the sucrose addition in terms of CO2 production and retention, even if lag leavening time was significantly (p < 0.05) shorter (about the half) and time of porosity appearance significantly (p < 0.05) longer (about 26%) with respect to S. cerevisiae alone. Results demonstrate that in the presence of sucrose, Z. mobilis can efficiently leaven a bread dough, thus providing innovation possibilities in the area of yeast-free leavened products.

BackgroundDiabetes mellitus (DM) is associated with enhanced platelet reactivity and impaired response to oral antiplatelet therapy, including clopidogrel. This post hoc analysis investigated the pharmacodynamic effects of ticagrelor versus clopidogrel loading dose (LD) in troponin‐negative acute coronary syndrome patients with or without DM undergoing percutaneous coronary intervention in the Ad Hoc PCI study. Methods and ResultsPatients randomized (1:1) to receive ticagrelor 180 mg LD or clopidogrel 600 mg LD were assessed by diabetic status. Platelet reactivity (P2Y12 reaction units [PRU] on VerifyNow® assay) was measured pre‐LD, at 0.5, 2, and 8 hours post‐LD, and at the end of the percutaneous coronary intervention. The primary endpoint was PRU levels 2 hours post‐LD; secondary endpoints included rates of high on‐treatment platelet reactivity (PRU≥208). Of 100 randomized patients, 51 received ticagrelor (DM, n=20; non‐DM, n=31) and 49 clopidogrel (DM, n=16; non‐DM, n=33). At 2 hours post‐LD, mean (SD) PRU levels in DM patients were 130.1 (111.7) with ticagrelor versus 287.6 (71.9) with clopidogrel (mean [95%CI] difference −157.5 [−225.3, −89.8]; P

Jung Rae Cho, Fabiana Rollini, Francesco Franchi, Elisabetta Ferrante, Dominick J Angiolillo University of Florida College of Medicine – Jacksonville, Jacksonville, FL, USA Abstract: Platelet activation with subsequent aggregation is a complex process leading to thrombus formation, which remains a key component for atherothrombotic manifestations, in particular myocardial infarction. Therefore, antiplatelet therapies are pivotal for the treatment of these patients. Current oral antiplatelet therapies used for secondary prevention of ischemic recurrences include aspirin and adenosine diphosphate P2Y12 platelet-receptor antagonists. However, despite these therapies, patients who have experienced a myocardial infarction remain at risk for ischemic recurrences. Therefore, more aggressive secondary prevention measures have been an area of research, including identifying additional targets modulating platelet-activation and -aggregation processes. Among these, thrombin-mediated platelet activation via protease-activated receptors (PARs) has been subject to extensive clinical investigation. Several PAR-1 receptor antagonists have been developed. However, vorapaxar is the only one that has completed large-scale clinical investigation. The present manuscript will provide an overview on the role of thrombin-mediated signaling, the impact of PAR-1 blockade with vorapaxar on ischemic and bleeding outcomes, and the potential role for vorapaxar in clinical practice. Keywords: platelet aggregation, antiplatelet agent, protease-activated receptor 1, vorapaxar

Baker’s yeast intolerance is rising among Western populations, where Saccharomyces cerevisiae is spread in fermented food and food components. Zymomonas mobilis is a bacterium commonly used in tropical areas to produce alcoholic beverages, and it has only rarely been considered for dough leavening probably because it only ferments glucose, fructose and sucrose, which are scarcely present in flour. However, through alcoholic fermentation, similarly to S. cerevisiae, it provides an equimolar mixture of ethanol and CO2 that can rise a dough. Here, we propose Z. mobilis as a new leavening agent, as an alternative to S. cerevisiae, overcoming its technological limit with different strategies: (1) adding glucose to the dough formulation; and (2) exploiting the maltose hydrolytic activity of Lactobacillus sanfranciscensis associated with Z. mobilis. CO2 production, dough volume increase, pH value, microbial counts, sugars consumption and ethanol production were monitored. Results suggest that glucose addition to the dough lets Z. mobilis efficiently leaven a dough, while glucose released by L. sanfranciscensis is not so well fermented by Z. mobilis, probably due to the strong acidification. Nevertheless, the use of Z. mobilis as a leavening agent could contribute to increasing the variety of baked goods alternative to those leavened by S. cerevisiae.

Ready-to-eat (RTE) vegetables belong to the convenience foods category: they offer features like freshness, commodity of use and good retention of nutritional qualities. Nevertheless, as the raw material is characterized by a high enzymatic content and water activity, it represents an excellent substrate for microorganisms. For these reason, microbial growth is a key factor in RTE product deterioration. Total bacterial count (TBC) was taken as the most relevant index to define hygiene and quality. Lactic acid bacteria, yeasts and moulds were present only occasionally. TBC was found lower when the product is packed under modified atmosphere. Gram-negative aerobic rods are dominant in air-packaged products, whilst the presence of Enterobacteriaceae becomes important in salads packaged under Modified Atmosphere. Pseudomonas fluorescens was the most frequently found species among the aerobic isolates, whilst for the Enterobacteriaceae strains no dominant species was found. These isolated strains were tested for their sensitivity against two natural antimicrobial compounds, carvacrol (essential oil, active in vapour form), and ethyl-lauroyl-arginate (LAE, water soluble). Sensitivity was compared with that evidenced for strains belonging to official collections. Near 60 % of the tested Gram negative bacteria were found sensitive to LAE at a concentration of 20 mg/L, and near 90 % at 50 mg/L. Instead, carvacrol antimicrobial activity seemed more strain specific and not evidenced against lactic acid bacteria (LAB). A higher antimicrobial effect was found when the two antimicrobials were used in association. This combined approach, effective both in vapour and liquid phase, can represent an innovative solution to increase shelf life of RTE products.

There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor. This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor. In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included VerifyNow P2Y 12 reaction units (PRU), light transmittance aggregometry, vasodilator-stimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7 time points. Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: −28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. Compared with placebo, the use of cangrelor in patients pretreated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162) [Display omitted] [ABSTRACT FROM AUTHOR]