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In recent years, there have been numerous recalls of frozen vegetable products due to Listeria monocytogenes contamination, which causes listeriosis. In pregnant women, listeriosis can cause miscarriage, stillbirth, and other serious complications. Manufacturing guidelines are created with the intention that frozen vegetables will be cooked prior to consumption. However, consumers may prepare and eat frozen vegetables without prior cooking. Therefore, it is necessary to assess behaviors that could be risky for L. monocytogenes exposure. A 10-question online survey was distributed to women between the ages of 18-54 to investigate frozen vegetable consumption behaviors. The prevalence of uncooked frozen vegetable consumption, reading preparation instructions, and listeriosis knowledge was assessed. Data were analyzed using logistic and ordered logit regression. Of 1,001 complete responses, 531 (53%) indicated that they consumed frozen vegetables in the past week, and of those 35.6% (n = 189) indicated that they consumed frozen vegetables without prior heating. Women who had not heard of listeriosis and had not read preparation instructions had significantly higher odds of uncooked frozen vegetable consumption (Odds Ratio (OR): 2.30, 95% Confidence Interval (CI): 1.48, 3.55; OR: 1.85, 95% CI: 1.13, 3.01, respectively). These results will guide future research on safe food handling practices for frozen vegetable products. The findings support the need for updating public health guidelines to include frozen vegetables as foods that are risky for listeriosis in pregnancy. Additionally, these findings have implications for future research to inform food policy governing labeling regulation on frozen vegetable products to reflect current consumer behavior., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Compared to the in-person Trier Social Stress Test (TSST), virtual reality (VR) variants reduce resource-intensity and improve standardization but induce stress with smaller effect sizes. However, higher cortisol reactivity is given for more immersive TSST-VRs. Immersivity depends on the VR-system, but perceived immersion may be targeted by exposure to, or interaction with the VR. We investigated whether stress reactivity towards the openly accessible OpenTSST VR can be enhanced by prior exposure to a sensorimotor game completed in VR as mediated by increased immersion. Therefore, N  = 58 healthy participants underwent the OpenTSST VR or its inbuilt control condition (placebo TSST-VR, pTSST-VR). Beforehand, participants completed a sensorimotor game either in VR or in real life. Stress was measured by means of self-reports, salivary cortisol concentrations, and salivary alpha-amylase (sAA) activity. Perceived immersion was assessed with the Igroup Presence Questionnaire (IPQ). The TSST-VR-group showed higher subjective stress than the pTSST-VR-group. Even though area under the curve measures indicated significant differences in cortisol levels between TSST-VR and pTSST-VR, this effect was not replicated in omnibus-analyses. Likewise, sAA was not responsive to stress. Our data suggests the OpenTSST VR does not reliably trigger physiological stress reactivity. Likewise, participants playing the VR-game before exposure to the TSST-VR did not show enhanced stress reactivity. Importantly, playing the VR-game did not lead to increased immersion (indicated by the IPQ), either. The key question resulting from our study is which manipulation may be fruitful to obtain a comparable stress response toward the TSST-VR compared to the in-person TSST.

Many studies have suggested that episodic memory is a generative process, but most computational models adopt a storage view. In this article, we present a model of the generative aspects of episodic memory. It is based on the central hypothesis that the hippocampus stores and retrieves selected aspects of an episode as a memory trace, which is necessarily incomplete. At recall, the neocortex reasonably fills in the missing parts based on general semantic information in a process we call semantic completion. The model combines two neural network architectures known from machine learning, the vector-quantized variational autoencoder (VQ-VAE) and the pixel convolutional neural network (PixelCNN). As episodes, we use images of digits and fashion items (MNIST) augmented by different backgrounds representing context. The model is able to complete missing parts of a memory trace in a semantically plausible way up to the point where it can generate plausible images from scratch, and it generalizes well to images not trained on. Compression as well as semantic completion contribute to a strong reduction in memory requirements and robustness to noise. Finally, we also model an episodic memory experiment and can reproduce that semantically congruent contexts are always recalled better than incongruent ones, high attention levels improve memory accuracy in both cases, and contexts that are not remembered correctly are more often remembered semantically congruently than completely wrong. This model contributes to a deeper understanding of the interplay between episodic memory and semantic information in the generative process of recalling the past., (© 2022 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

The complex environment of a produce packinghouse can facilitate the spread of pathogens such as Listeria monocytogenes in unexpected ways. This can lead to finished product contamination and potential foodborne disease cases. There is a need for simulation-based decision support tools that can test different corrective actions and are able to account for a facility's interior cross-contamination dynamics. Thus, we developed agent-based models of Listeria contamination dynamics for two produce packinghouse facilities; agents in the models represented equipment surfaces and employees, and models were parameterized using observations, values from published literature and expert opinion. Once validated with historical data from Listeria environmental sampling, each model's baseline conditions were investigated and used to determine the effectiveness of corrective actions in reducing prevalence of agents contaminated with Listeria and concentration of Listeria on contaminated agents. Evaluated corrective actions included reducing incoming Listeria, modifying cleaning and sanitation strategies, and reducing transmission pathways, and combinations thereof. Analysis of Listeria contamination predictions revealed differences between the facilities despite their functional similarities, highlighting that one-size-fits-all approaches may not always be the most effective means for selection of corrective actions in fresh produce packinghouses. Corrective actions targeting Listeria introduced in the facility on raw materials, implementing risk-based cleaning and sanitation, and modifying equipment connectivity were shown to be most effective in reducing Listeria contamination prevalence. Overall, our results suggest that a well-designed cleaning and sanitation schedule, coupled with good manufacturing practices can be effective in controlling contamination, even if incoming Listeria spp. on raw materials cannot be reduced. The presence of water within specific areas was also shown to influence corrective action performance. Our findings support that agent-based models can serve as effective decision support tools in identifying Listeria-specific vulnerabilities within individual packinghouses and hence may help reduce risks of food contamination and potential human exposure., Competing Interests: Drs. Ivanek and Wiedmann are named as co-inventors, along with Dr. Zoellner, on an algorithm that uses an in silico method to reproduce the behavior of biological contaminants in built environments, which was licensed to iFoodDecisionSciences, Inc. Dr. Zoellner is presently employed by iFoodDecisionSciences, Inc., a company that provides industry with modeling and data analysis tools. This commercial affiliation did not play a role in the study design, data analysis, or preparation of the manuscript and only provided financial support in the form of an author’ salaries. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Sphingosine-1-phosphate (S1P) is a signaling lipid and crucial in vascular protection and immune response. S1P mediated processes involve regulation of the endothelial barrier, blood pressure and S1P is the only known inducer of lymphocyte migration. Low levels of circulatory S1P correlate with severe systemic inflammatory syndromes such as sepsis and shock states, which are associated with endothelial barrier breakdown and immunosuppression. We investigated whether S1P levels are affected by sterile inflammation induced by cardiac surgery., Materials and Methods: In this prospective observational study we included 46 cardiac surgery patients, with cardiopulmonary bypass (CPB, n=31) and without CPB (off-pump, n=15). Serum-S1P, S1P-sources and carriers, von-Willebrand factor (vWF), C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were measured at baseline, post-surgery and at day 1 (POD 1) and day 4 (POD 4) after surgical stimulus., Results: Median S1P levels at baseline were 0.77 nmol/mL (IQR 0.61-0.99) and dropped significantly post-surgery. S1P was lowest post-surgery with median levels of 0.37 nmol/mL (IQR 0.31-0.47) after CPB and 0.46 nmol/mL (IQR 0.36-0.51) after off-pump procedures (P<0.001). The decrease of S1P was independent of surgical technique and observed in all individuals. In patients, in which S1P levels did not recover to preoperative baseline ICU stay was longer and postoperative inflammation was more severe. S1P levels are associated with its sources and carriers and vWF, as a more specific endothelial injury marker, in different phases of the postoperative course. Determination of S1P levels during surgery suggested that also the anticoagulative effect of heparin might influence systemic S1P., Discussion: In summary, serum-S1P levels are disrupted by major cardiac surgery. Low S1P levels post-surgery may play a role as a new marker for severity of cardiac surgery induced inflammation. Due to well-known protective effects of S1P, low S1P levels may further contribute to the observed prolonged ICU stay and worse clinical status. Moreover, we cannot exclude a potential inhibitory effect on circulating S1P levels by heparin anticoagulation during surgery, which would be a new pro-inflammatory pleiotropic effect of high dose heparin in patients undergoing cardiac surgery., Competing Interests: SK declares the following competing interests: He received research support by Ambu, E.T.View Ltd, Fisher & Paykel, Pfizer and Xenios; lecture honorarium from Arjo-Huntleigh, Astellas, Astra, Basilea, Bard, Baxter, Biotest, CSL Behring, Cytosorbents, Fresenius, Gilead, MSD, Orion, Pfizer, Philips, Sedana, Sorin, Xenios and Zoll. SK received consultant honorarium from AMOMED, Astellas, Baxter, Bayer, Fresenius, Gilead, MSD, Pfizer and Xenios. MW declares the following competing interests of funding from Sartorius lung research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Greiwe, Moritz, Amschler, Poppe, Sarwari, Nierhaus, Kluge, Reichenspurner, Zoellner, Schwedhelm, Daum, Tampe and Winkler.)

Food facilities need time- and cost-saving methods during the development and optimization of environmental monitoring for pathogens and their surrogates. Rapid virtual experimentation through in silico modeling can alleviate the need for extensive real-world, trial-and-error style program design. Two agent-based models of fresh-cut produce facilities were developed as a way to simulate the dynamics of Listeria in the built environment by modeling the different surfaces of equipment and employees in a facility as agents. Five sampling schemes at three time points were evaluated in silico on their ability to locate the presence of Listeria contamination in a facility with sample sites for each scheme (i.e., scenario, as modeled using scenario analysis) based on the following: the facilities' current environmental monitoring program (scenario 1), Food and Drug Administration recommendations (scenario 2), random selection (scenario 3), sites exclusively from zone 3 (i.e., sites in the production room but not directly adjacent to food contact surfaces) (scenario 4), or model prediction of elevated risk of contamination (scenario 5). Variation was observed between the scenarios on how well the Listeria prevalence of the virtually collected samples reflected the true prevalence of contaminated agents in the modeled operation. The zone 3 only (scenario 4) and model-based (scenario 5) sampling scenarios consistently overestimated true prevalence across time, suggesting that those scenarios could provide a more sensitive approach for determining if Listeria is present in the operation. The random sampling scenario (scenario 3) may be more useful for operations looking for a scheme that is most likely to reflect the true prevalence. Overall, the developed models allow for rapid virtual experimentation and evaluation of sampling schemes specific to unique fresh-cut produce facilities. IMPORTANCE Programs such as environmental monitoring are used to determine the state of a given food facility with regard to the presence of environmental pathogens, such as Listeria monocytogenes, that could potentially cross-contaminate food product. However, the design of environmental monitoring programs is complex, and there are infinite ways to conduct the sampling that is required for these programs. Experimentally evaluating sampling schemes in a food facility is time-consuming, costly, and nearly impossible. Therefore, the food industry needs science-based tools to aid in developing and refining sampling plans that reduce the risk of harboring contamination. Two agent-based models of two fresh-cut produce facilities reported here demonstrate a novel way to evaluate how different sampling schemes can be rapidly evaluated across multiple time points as a way to understand how sampling can be optimized in an effort to locate the presence of Listeria in a food facility.

Studies applying the self-determination theory have shown that intrinsic motivation and autonomous regulation lead to job satisfaction and to better job performance. What has not been worked out clearly yet are the effects of extrinsic motivation and controlled regulation on affect, job performance and job satisfaction. However, it has been described that controlled regulation is often necessary for mundane tasks. In anaesthesiology, routine daily tasks can be perceived as mundane by those who have achieved a certain level of training (e.g., consultants). Therefore, it was hypothesised that consultants have high expressions of all motivational qualities. Furthermore, it was hypothesised that job satisfaction of anaesthesiologists is correlated with autonomous motivation. The hypotheses were tested in a cross-sectional study design within a group of anaesthesiologists. The study participants reported the same pattern throughout the motivational continuum. Consultants reported the highest levels of all motivational qualities, including controlled regulation, as well as the highest levels of job satisfaction. Junior residents reported high levels of amotivation and extrinsic regulation. The lowest levels of identified regulation and job satisfaction were reported by the group of attendings. Job satisfaction was positively correlated with intrinsic motivation and negatively correlated with amotivation. Therefore, our findings from the field of anaesthesiology show that the expressions of high levels of controlled regulation might be necessary for specialists to engage in mundane daily tasks. Intrinsic motivation and autonomous regulation are necessary for job satisfaction and the presence of controlled regulation and extrinsic behavioural regulation have no declining effects. Furthermore, the decrease of amotivation will lead to enhanced job satisfaction and the resulting consequences will be extensive. Junior residents need to be supported with the aim to enhance their feeling of autonomy and competence in order to decrease amotivation and to foster autonomous regulation and hence to increase job satisfaction and well-being. Further special focus should be on attendings to counteract their lacking identification with the job. Hereby, the provision of feedback and professional perspectives might foster the process of re-identification.

Objective: Since the 1970s, the operating microscope (OM) has been a standard for visualization and illumination of the surgical field in spinal microsurgery. However, due to its limitations (e.g., size, costliness, and the limited movability of the binocular lenses, in addition to discomfort experienced by surgeons due to the posture required), there are efforts to replace the OM with exoscopic video telescopes. The authors evaluated the feasibility of a new 3D exoscope as an alternative to the OM in spine surgeries., Methods: Patients with degenerative pathologies scheduled for single-level lumbar or cervical spinal surgery with use of a high-definition 3D exoscope were enrolled in a prospective cohort study between January 2019 and September 2019. Age-, sex-, body mass index-, and procedure-matched patients surgically treated with the assistance of the OM served as the control group. Operative baseline and postoperative outcome parameters were assessed. Periprocedural handling, visualization, and illumination by the exoscope, as well as surgeons' comfort level in terms of posture, were scored using a questionnaire., Results: A 3D exoscope was used in 40 patients undergoing lumbar posterior decompression (LPD) and 20 patients undergoing anterior cervical discectomy and fusion (ACDF); an equal number of controls in whom an OM was used were studied. Compared with controls, there were no significant differences for mean operative time (ACDF: 132 vs 116 minutes; LPD: 112 vs 113 minutes) and blood loss (ACDF: 97 vs 93 ml; LPD: 109 vs 55 ml) as well as postoperative improvement of symptoms (ACDF/Neck Disability Index: p = 0.43; LPD/Oswestry Disability Index: p = 0.76). No intraoperative complications occurred in either group. According to the attending surgeon, the intraoperative handling of instruments was rated to be comparable to that of the OM, while the comfort level of the surgeon's posture intraoperatively (especially during "undercutting" procedures) was rated as superior. In cases of ACDF procedures and long approaches, depth perception, image quality, and illumination were rated as inferior when compared with the OM. By contrast, for operating room nursing staff participating in 3D exoscope procedures, the visualization of intraoperative process flow and surgical situs was rated to be superior to the OM, especially for ACDF procedures., Conclusions: A 3D exoscope seems to be a safe alternative for common spinal procedures with the unique advantage of excellent comfort for the surgical team, but the drawback is the still slightly inferior visualization/illumination quality compared with the OM.

Protocols for "Enhanced recovery after surgery (ERAS)" are on the rise in different surgical disciplines and represent one of the most important recent advancements in perioperative medical care. In cardiac surgery, only few ERAS protocols have been described in the past. At University Heart Center Hamburg, Germany, we invented an ERAS protocol for patients undergoing minimally invasive cardiac valve surgery. In this retrospective single center study, we aimed to describe the implementation of our ERAS program and to evaluate the results of the first 50 consecutive patients. Our ERAS protocol was developed according to a modified Kern cycle by an expert group, literature search, protocol creation and pilot implementation in the clinical practice. Data of the first 50 consecutive patients undergoing minimally invasive cardiac valve surgery were analysed retrospectively. The key features of our multidisciplinary ERAS protocol are physiotherapeutic prehabilitation, minimally invasive valve surgery techniques, modified cardiopulmonary bypass management, fast-track anaesthesia with on- table extubation and early mobilisation. A total of 50 consecutive patients (mean age of 51.9±11.9 years, mean STS score of 0.6±0.3) underwent minimally-invasive mitral or aortic valve surgery. The adherence to the ERAS protocol was high and neither protocol related complications nor in-hospital mortality occurred. 12% of the patients developed postoperative atrial fibrillation, postoperative delirium emerged in two patients and reintubation was required in one patient. Intensive care unit stay was 14.0±7.4 hours and total hospital stay 6.2±2.9 days. Our ERAS protocol is feasible and safe in minimally-invasive cardiac surgery setting and has a clear potential to improve patients outcome., Competing Interests: The authors have declared that no competing interests exist.

Frozen foods do not support the growth of Listeria monocytogenes (LM) and should be handled appropriately for safety. However, consumer trends regarding preparation of some frozen foods may contribute to the risk of foodborne listeriosis, specifically when cooking instructions are not followed and frozen products are instead added directly to smoothies or salads. A quantitative microbial risk assessment model FFLLoRA (Frozen Food Listeria Lot Risk Assessment) was developed to assess the lot-level listeriosis risk due to LM contamination in frozen vegetables consumed as a ready-to-eat food. The model was designed to estimate listeriosis risk per serving and the number of illnesses per production lot of frozen vegetables contaminated with LM, considering individual facility factors such as lot size, prevalence of LM contamination, and consumer handling prior to consumption. A production lot of 1 million packages with 10 servings each was assumed. When at least half of the servings were cooked prior to consumption, the median risk of invasive listeriosis per serving in both the general and susceptible population was <1.0 × 10 -16 with the median (5th, 95th percentiles) predicted number of illnesses per lot as 0 (0, 0) and 0 (0, 1) under the exponential and Weibull-gamma dose-response functions, respectively. In scenarios in which all servings are consumed as ready-to-eat, the median predicted risk per serving was 1.8 × 10 -13 and 7.8 × 10 -12 in the general and susceptible populations, respectively. The median (5th, 95th percentile) number of illnesses was 0 (0, 0) and 0 (0, 6) for the exponential and Weibull-Gamma models, respectively. Classification tree analysis highlighted initial concentration of LM in the lot, temperature at which the product is thawed, and whether a serving is cooked as main predictors for illness from a lot. Overall, the FFLLoRA provides frozen food manufacturers with a tool to assess LM contamination and consumer behavior when managing rare and/or minimal contamination events in frozen foods.

Purpose: To evaluate the performance of a novel camera-based breathing navigation system in respiratory-triggered (CRT) 3D-magnetic resonance cholangiopancreatography (MRCP) at 3T MRI., Methods: Two 3D-MRCP data sets were acquired subsequently within one imaging session with traditional respiratory belt- (BRT) or camera- (CRT) based triggering in 28 patients. Overall image quality, blurring, motion artifacts and discernibility of the pancreaticobiliary tree (PBT) structures were scored on a 4-point scale retrospectively by 2 radiologists. The contrast ratio between the common bile duct and its adjacent tissue was measured by region-of-interest (ROI) analysis. The signal intensity increase at the duct boundaries was quantified by line profiles to objectify blurring and motion artifacts. The extracted respiratory signal curves were analyzed for signal quality and trigger timing., Results: Total scan time was 72 s for both acquisitions. CRT yielded significantly better ratings in image quality, background suppression, blurring and discernibility of PBT structures compared to BRT. Contrast ratios were significantly higher in CRT (0.94 ± 0.03) than in BRT (0.93 ± 0.03) exams; paired t test P = 0.0017. Line profile slopes through the common bile duct revealed significantly higher values in CRT (42.23 ± 8.74% of maximum intensity/mm) compared to BRT (36.06 ± 8.96% of maximum intensity/mm; paired t test P < 0.0001). Camera-derived respiratory signal curves showed a higher SNR, lower standard deviation of the signal amplitude and less incorrect triggering than the respiratory belt-derived respiratory signal curves., Conclusion: Camera-based respiratory triggering significantly improves image quality of 3D-MRCP compared to conventional respiratory belt triggering., (Copyright © 2019. Published by Elsevier B.V.)

Detection of pathogens in food processing facilities by routine environmental monitoring (EM) is essential to reduce the risk of foodborne illness but is complicated by the complexity of equipment and environment surfaces. To optimize design of EM programs, we developed EnABLe ("Environmental monitoring with an Agent-Based Model of Listeria"), a detailed and customizable agent-based simulation of a built environment. EnABLe is presented here in a model system, tracing Listeria spp. (LS) (an indicator for conditions that allow the presence of the foodborne pathogen Listeria monocytogenes) on equipment and environment surfaces in a cold-smoked salmon facility. EnABLe was parameterized by existing literature and expert elicitation and validated with historical data. Simulations revealed different contamination dynamics and risks among equipment surfaces in terms of the presence, level and persistence of LS. Grouping of surfaces by their LS contamination dynamics identified connectivity and sanitary design as predictors of contamination, indicating that these features should be considered in the design of EM programs to detect LS. The EnABLe modeling approach is particularly timely for the frozen food industry, seeking science-based recommendations for EM, and may also be relevant to other complex environments where pathogen contamination presents risks for direct or indirect human exposure.

Occurrence of Listeria monocytogenes (Lm), the causative agent of listeriosis, in food processing facilities presents considerable challenges to food producers and food safety authorities. Design of an effective, risk-based environmental monitoring (EM) program is essential for finding and eliminating Lm from the processing environment to prevent product contamination. A scoping review was conducted to collate and synthesize available research and guidance materials on Listeria EM in food processing facilities. An exhaustive search was performed to identify all available research, industry and regulatory documents, and search results were screened for relevance based on eligibility criteria. After screening, 198 references were subjected to an in-depth review and categorized according to objectives for conducting Listeria sampling in food processing facilities and food sector. Mapping of the literature revealed research and guidance gaps by food sector, as fresh produce was the focus in only 10 references, compared to 72 on meat, 52 on fish and seafood, and 50 on dairy. Review of reported practices and guidance highlighted key design elements of EM, including the number, location, timing and frequency of sampling, as well as methods of detection and confirmation, and record-keeping. While utilization of molecular subtyping methods is a trend that will continue to advance understanding of Listeria contamination risks, improved study design and reporting standards by researchers will be essential to assist the food industry optimize their EM design and decision-making. The comprehensive collection of documents identified and synthesized in this review aids continued efforts to minimize the risk of Lm contaminated foods., (© 2018 Institute of Food Technologists®.)

Fresh produce supply chains present variable and diverse conditions that are relevant to food quality and safety because they may favor microbial growth and survival following contamination. This study presents the development of a simulation and visualization framework to model microbial dynamics on fresh produce moving through postharvest supply chain processes. The postharvest supply chain with microbial travelers (PSCMT) tool provides a modular process modeling approach and graphical user interface to visualize microbial populations and evaluate practices specific to any fresh produce supply chain. The resulting modeling tool was validated with empirical data from an observed tomato supply chain from Mexico to the United States, including the packinghouse, distribution center, and supermarket locations, as an illustrative case study. Due to data limitations, a model-fitting exercise was conducted to demonstrate the calibration of model parameter ranges for microbial indicator populations, i.e., mesophilic aerobic microorganisms (quantified by aerobic plate count and here termed APC) and total coliforms (TC). Exploration and analysis of the parameter space refined appropriate parameter ranges and revealed influential parameters for supermarket indicator microorganism levels on tomatoes. Partial rank correlation coefficient analysis determined that APC levels in supermarkets were most influenced by removal due to spray water washing and microbial growth on the tomato surface at postharvest locations, while TC levels were most influenced by growth on the tomato surface at postharvest locations. Overall, this detailed mechanistic dynamic model of microbial behavior is a unique modeling tool that complements empirical data and visualizes how postharvest supply chain practices influence the fate of microbial contamination on fresh produce. IMPORTANCE Preventing the contamination of fresh produce with foodborne pathogens present in the environment during production and postharvest handling is an important food safety goal. Since studying foodborne pathogens in the environment is a complex and costly endeavor, computer simulation models can help to understand and visualize microorganism behavior resulting from supply chain activities. The postharvest supply chain with microbial travelers (PSCMT) model, presented here, provides a unique tool for postharvest supply chain simulations to evaluate microbial contamination. The tool was validated through modeling an observed tomato supply chain. Visualization of dynamic contamination levels from harvest to the supermarket and analysis of the model parameters highlighted critical points where intervention may prevent microbial levels sufficient to cause foodborne illness. The PSCMT model framework and simulation results support ongoing postharvest research and interventions to improve understanding and control of fresh produce contamination., (Copyright © 2018 American Society for Microbiology.)

Background: Direct-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort., Methods: This retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up., Results: DAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16-0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up., Conclusions: Effective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.

Background: Sepsis is defined as a dysregulated immune response to infection. Impaired immune response in sepsis, often described as endotoxin tolerance, is characterized by unresponsiveness of monocytes on lipopolysaccharide (LPS) stimulation to release tumor necrosis factor α (TNFα). Furthermore, decreased monocyte surface protein expression of human leucocyte antigen DR (HLA-DR) is a marker for changes of the innate immune response during sepsis. Quantitative polymerase chain reaction (qPCR) and flow-cytometry (FACS) have been used to measure protein or gene expression of HLA-DR. We aimed to determine whether changes in mRNA expression of HLA-DR are associated with impaired TNFα response in human sepsis., Methods: Surface protein together with mRNA expression of HLA-DR were measured by FACS and qPCR in a cohort of 9 sepsis patients and compared to 10 pre-operative control patients in a prospective study. In addition, 20 patients with post-surgical inflammation, 20 patients with sepsis or septic shock were included and TNFα was determined following ex vivo stimulation of whole blood with 500 pg/mL LPS. Total RNA was prepared from whole blood and subjected to qPCR analysis for expression analysis of HLA-DR alpha (HLA-DRA) to correlate TNFα response with HLA-DRA expression., Results: Patients with sepsis presented higher numbers of monocytes in peripheral blood (P<0.001) but decreased surface protein and mRNA HLA-DR levels when compared to controls. In all patients mRNA expression of HLA-DRA was decreased by approximately 70% compared to controls (P<0.01) and was lowest in patients with sepsis or septic shock (P<0.01). TNFα response to LPS was decreased in all patients (median 319 pg/mL versus controls 1256 pg/mL; P<0.01) and lowest in patients with sepsis or septic shock (median 128 pg/mL; P<0.01). HLA-DRA correlated positively with TNFα response in all study participants (r +0.60, P<0.001) and within patients (r +0.67, P<0.001). The TNFα:HLA-DRA ratio correlated negatively with severity and the Sequential Organ Failure Assessment (SOFA) score (Spearman's rho -0.59, P<0.001)., Conclusion: In this study, HLA-DRA expression was associated with a functional assay of the innate immune response. Future interventional studies aimed at the immune response during sepsis could make use of these methods for optimizing target groups based on biological plausibility and intervention effectiveness.

Background: Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular function and pathogen defense. Direct NO measurement in patients is unfeasible because of its short half-life. Surrogate markers for NO bioavailability are substrates of NO generating synthase (NOS): L-arginine (lArg) and homoarginine (hArg) together with the inhibitory competitive substrate asymmetric dimethylarginine (ADMA). In immune cells ADMA is cleaved by dimethylarginine-dimethylaminohydrolase-2 (DDAH2). The aim of this study was to investigate whether concentrations of surrogate markers for NO bioavailability are associated with sepsis severity., Method: This single-center, prospective study involved 25 controls and 100 patients with surgical trauma (n = 20), sepsis (n = 63), or septic shock (n = 17) according to the Sepsis-3 definition. Plasma lArg, hArg, and ADMA concentrations were measured by mass spectrometry and peripheral blood mononuclear cells (PBMCs) were analyzed for DDAH2 expression., Results: lArg concentrations did not differ between groups. Median (IQR) hArg concentrations were significantly lower in patient groups than controls, being 1.89 (1.30-2.29) μmol/L (P < 0.01), with the greatest difference in the septic shock group, being 0.74 (0.36-1.44) μmol/L. In contrast median ADMA concentrations were significantly higher in patient groups compared to controls, being 0.57 (0.46-0.65) μmol/L (P < 0.01), with the highest levels in the septic shock group, being 0.89 (0.56-1.39) μmol/L. The ratio of hArg:ADMA was inversely correlated with disease severity as determined by the Sequential Organ Failure Assessment (SOFA) score. Receiver-operating characteristic analysis for the presence or absence of septic shock revealed equally high sensitivity and specificity for the hArg:ADMA ratio compared to the SOFA score. DDAH2 expression was lower in patients than controls and lowest in the subgroup of patients with increasing SOFA., Conclusions: In patients with sepsis, plasma hArg concentrations are decreased and ADMA concentrations are increased. Both metabolites affect NO metabolism and our findings suggest reduced NO bioavailability in sepsis. In addition, reduced expression of DDAH2 in immune cells was observed and may not only contribute to blunted NO signaling but also to subsequent impaired pathogen defense.

Quality and safety of fresh produce are important to public health and maintaining commerce between Mexico and USA. While preventive practices can reduce risks of contamination and are generally successful, the variable environment of the supply chain of fresh produce can be suitable for introduction or proliferation of pathogenic microorganisms. As routine surveillance of these pathogens is not practical, indicator microorganisms are used to assess the sanitary conditions of production and handling environments. An opportunity exists to use indicators on fresh produce to measure how handling and transport from field to market may affect microbial populations that contribute to their quality or safety. The objective was to quantify indicator microorganisms on tomatoes sampled along the supply chain during the harvest year, in order to observe the levels and changes of populations at different locations. Roma tomatoes (n=475) were taken from the same lots (n=28) at four locations of the postharvest supply chain over five months: at arrival to and departure from the packinghouse in México, at the distribution center in Texas, and at retail in USA. Samples were analyzed individually for four microbial populations: aerobic plate count (APC), total coliforms (TC), generic Escherichia coli, and yeasts and molds (YM). APC population differed (p<0.05) from 1.9±1.1, 1.7±1.1, 2.3±1.1 and 3.5±1.4logCFU/g at postharvest, packing, distribution center and supermarket, respectively. TC populations were <1logCFU/g at postharvest, increased at packing (0.7±1.0logCFU/g), decreased in distribution (0.4±0.8logCFU/g) and increased in supermarkets (1.4±1.5logCFU/g). Generic E. coli was not identified from coliform populations in this supply chain. YM populations remained <1logCFU/g, with the exception of 1.1±1.3logCFU/g at supermarkets and tomatoes were not visibly spoiled. The levels reported from this pilot study demonstrated the dynamics within populations as influenced by time and conditions in one supply chain during a harvest year, while the large variances in some locations indicate opportunities for improvement. Overall, packinghouse and supermarket locations were identified as crucial points to control microbial safety risks., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Sphingosine-1-phosphate (S1P) is a signaling lipid that regulates pathophysiological processes involved in sepsis progression, including endothelial permeability, cytokine release, and vascular tone. The aim of this study was to investigate whether serum-S1P concentrations are associated with disease severity in patients with sepsis., Methods: This single-center prospective-observational study includes 100 patients with systemic inflammatory response syndrome (SIRS) plus infection (n = 40), severe sepsis (n = 30), or septic shock (n = 30) and 214 healthy blood donors as controls. Serum-S1P was measured by mass spectrometry. Blood parameters, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), lactate, and white blood cells (WBCs), were determined by routine assays. The Sequential Organ Failure Assessment (SOFA) score was generated and used to evaluate disease severity., Results: Serum-S1P concentrations were lower in patients than in controls (P < 0.01), and the greatest difference was between the control and the septic shock groups (P < 0.01). Serum-S1P levels were inversely correlated with disease severity as determined by the SOFA score (P < 0.01) as well as with IL-6, PCT, CRP, creatinine, lactate, and fluid balance. A receiver operating characteristic analysis for the presence or absence of septic shock revealed equally high sensitivity and specificity for S1P compared with the SOFA score. In a multivariate logistic regression model calculated for prediction of septic shock, S1P emerged as the strongest predictor (P < 0.001)., Conclusions: In patients with sepsis, serum-S1P levels are dramatically decreased and are inversely associated with disease severity. Since S1P is a potent regulator of endothelial integrity, low S1P levels may contribute to capillary leakage, impaired tissue perfusion, and organ failure in sepsis.

Sprouts have gained popularity worldwide due to their nutritional values and health benefits. The fact that their consumption has been associated with numerous outbreaks of foodborne illness threatens the $250 million market that this industry has established in the United States. Therefore, sprout manufacturers have utilized the U.S. Food and Drug Administration recommended application of 20,000 ppm of calcium hypochlorite solution to seeds before germination as a preventative method. Concentrations of up to 200 ppm of chlorine wash are also commonly used on sprouts. However, chlorine-based treatment achieves on average only 1- to 3-log reductions in bacteria and is associated with negative health and environmental issues. The search for alternative strategies has been widespread, involving chemical, biological, physical, and hurdle processes that can achieve up to 7-log reductions in bacteria in some cases. The compilation here of the current scientific data related to these techniques is used to compare their efficacy for ensuring the microbial safety of sprouts and their practicality for commercial producers. Of specific importance for alternative seed and sprout treatments is maintaining the industry-accepted germination rate of 95% and the sensorial attributes of the final product. This review provides an evaluation of suggested decontamination technologies for seeds and sprouts before, during, and after germination and concludes that thermal inactivation of seeds and irradiation of sprouts are the most practical stand-alone microbial safety interventions for sprout production.

Importance of the Field: Ribavirin is a broad spectrum antiviral agent that is used with pegylated IFN (Peg-IFN) for HCV treatment. Ribavirin does not significantly reduce HCV viral load when used alone but increases rates of sustained virologic response (SVR) when combined with Peg-IFN. HCV genotype 1 infected patients require higher doses of ribavirin administered for a longer duration of time versus HCV genotypes 2 and 3 patients who respond effectively to Peg-IFN with lower doses of ribavirin and shorter duration of therapy. Higher serum concentrations of ribavirin are associated with higher response rates but also higher rates of hemolytic anemia which is a dose limiting side effect. Alternatives to current therapy are under clinical evaluation., Areas Covered in This Review: Systematic literature review of ribavirin use in HCV patients from 1995 to 2009 was conducted., What the Reader Will Gain: To review the efficacy and safety of ribavirin in current HCV treatment and in new therapies in Phase III clinical trials., Take Home Message: Ribavirin is a drug which is essential to produce higher SVR rates both with Peg-IFN and HCV protease inhibitors currently in Phase III clinical trials. Thus, ribavirin is and will remain an important drug to achieving higher SVR rates in HCV infected persons.