Human Surrogates Research Articles

Investigating mechanical properties for developing a human infant cranial bone surrogate in pediatric craniofacial surgery

Investigating mechanical properties for developing a human infant cranial bone surrogate in pediatric craniofacial surgery

Use of a Porcine Cadaver Model as a Human Surrogate for Behind Armor Blunt Trauma

Abstract Current body armor design evaluation is based on legacy backface deformation criteria for protection, despite limited medical basis. This uniform protection approach, which does not account for anatomical and physiological variability within the torso, may result in heavy armors that limit Warfighter mobility. To optimize armor design, live animal experimentation must be conducted to assess regional injury tolerances; however, the animal and human must first be compared to determine the animal model's viability as a surrogate for thoracoabdominal behind armor blunt trauma (BABT) response. Here, 74 BABT impacts were conducted using ten mid-sized male post-mortem human subjects (PMHS) and ten 40-kg porcine cadavers in matched testing conditions over the lungs, liver, and sternum. Injury risk functions were generated from experimental data and compared across surrogates at each body region. The PMHS and 40-kg porcine cadaver correlated well for chest wall injuries in the lung region, and similarities were noted in high-severity impacts to the liver. Further, assessment of the backface intrusion injury risk function showed regional tolerance differences between anatomical regions, highlighting the need for separate region-specific design criteria. These results indicate that the 40-kg porcine cadaver was an appropriate torso surrogate for certain PMHS regions, such as the ribcage overlaying the lungs and the unprotected liver, in BABT conditions. As this study used cadaveric tissue, future studies should investigate the physiological components of BABT-induced injury in a live animal model, focusing on quantifying regional injury tolerances toward armor design optimization.

Antiviral activity of Polygonum aviculare extract against murine norovirus as norovirus surrogate and its application in model food

Norovirus is a major cause of acute gastroenteritis, with vaccines or antiviral therapy yet to be approved. Polygonum aviculare is a medicinal plant with various physiological properties. In this study, the antiviral activity of Polygonum aviculare extract (PAE) was examined against murine norovirus (MNV-1), a human norovirus surrogate. Pre-treatment with PAE suppressed MNV-1, achieving a half-maximal inhibitory concentration (IC50) of 78.4 μg/mL. TEM images revealed viral morphological changes following PAE treatment, indicating the antiviral effect of PAE. Treatment with 100 and 200 μg/mL PAE for 1 h significantly reduced the temperature-dependent antiviral PAE activity at all temperatures. Time-of-addition test results also demonstrated PAE antiviral activity in cell pre-, co-, and post-treatments, with slightly higher activity detected upon cell pre-treatment. HPLC analysis identified avicularin and myricitrin peaks, and LC-QTOF/MS determined phenolic acids and flavonoids as the main constituents. Our findings confirmed the antiviral efficacy of myricetin and quercetin at concentrations of 50 and 100 μM in co-treatment experiments. Upon inoculating the cabbage surface with MNV-1, PAE treatment at 4 or 25 °C reduced MNV-1 plaque formation. Collectively, our findings suggest that PAE could effectively inactivate norovirus and demonstrate promising potential as a natural antiviral agent for food safety.

Effect of data censoring on thoracic injury risk curves

Objective The first objective was to evaluate the effect of using less censored (i.e., exact and interval-censored) data on thoracic injury risk curves and the resulting injury probabilities. The second objective was to generate new injury risk curves to predict Abbreviated Injury Scale (AIS) 3+ rib fractures based on chest deflection. Methods Two data sets consisting of postmortem human surrogate (PMHS) tests with multipoint chest deflection measurements were compiled: A less censored data set consisting of exact and interval-censored data and a doubly censored data set consisting of left- and right-censored data. Chest deflection data from both data sets were processed in a consistent manner to calculate the maximum deflections at different locations across the chest. Survival analysis methods were used to generate nonparametric and parametric injury risk curves for serious skeletal injury. The total sample sizes and proportions of less censored data used to generate the risk curves were varied for each curve to evaluate the effects of sample size and less censored data on risk curve shape and predicted injury thresholds. Results Increasing the proportion of less censored data resulted in steeper injury risk curves and a higher predicted risk for a given amount of deflection. Differences in injury risk were more pronounced in the upper half of the injury risk curves. Introducing less censored data also produced narrower confidence intervals. At a total sample size of 79, increasing the percentage of less censored data from 0 to 30 had minimal effect on the shape of the risk curve. Conclusions Doubly censored chest deflection data have historically been used to generate thoracic injury risk curves for frontal motor vehicle crash events. This study found that incorporating less censored data into thoracic injury risk curves meaningfully affected the shape of the injury risk curves and their resulting injury risk predictions. All of the injury risk curves generated in the study predicted a lower threshold for serious rib fracture injury compared to previously developed injury risks curves that are currently in use in the field. Based on the results of this study, adding less censored data to injury risk curves should be strongly considered to improve thoracic injury risk curve prediction and confidence, especially for smaller sample sizes.

Determination of distal fibula fracture for prediction of ankle injuries

Objective This study quantified the local fracture tolerance of the distal fibula. The purpose of this data is to refine the understanding of ankle fracture tolerance in the population and enhance injury prediction by computational tools. Methods Fracture patterns of the fibula were obtained from the US National Highway Traffic Safety Administration (NHTSA) Crash Injury Research Engineering Network (CIREN). Of 143 cases of ankle injury, 120 included fibula fracture, many of which accompanied by radiology images. The most common fibula fracture type was a Weber C fracture, which was then used as the testing target to replicate with postmortem human surrogates. Isolated distal fibulae (male and female, across a wide anthropometric range) were subjected to quasi-static lateral-medial four-point bending superimposed on axial precompression. Results Of the 20 specimens tested, 17 fractured in compression and bending, two fractured in compression, bending, and shear, and one did not fracture upon the imposed displacement. Fractures occurring outside of the target testing span were treated as right-censored data points. Fracture patterns varied among specimens, with oblique fractures being most common, followed by segmental fractures. At failure, compressive force ranged from 77 N to 370 N and bending moment from 17 Nm to 47 Nm. Conclusions From the 19 fractured specimens, the variety of fracture patterns observed were generally consistent with the range of fibula fracture types and locations commonly observed in the field. While comparative studies with fibula specimens are largely absent from literature, comparison of this study to other long bones (radius and ulna) show that bending moment at fracture is similar. To the author’s knowledge, this is the first study to quantify the fracture tolerance of isolated distal fibulae under loading conditions representative of ankle injury mechanisms in motor vehicle collisions. By combining the results of this study with complementary results from parallel tibia-focused experiments (currently in-press), these results will aid development of tissue-level lower leg fracture prediction of human body models, thus enhancing prediction of ankle injury during safety assessment simulations. Specifically, the fracture tolerance information might generate an injury risk function to guide tissue-level injury prediction with human body models.

Inactivation of Hepatitis A Virus and Feline Calicivirus on Model Food Contact Surfaces by Ultraviolet Light (UV-C) Systems.

Food contact surfaces can harbor and transmit pathogens leading to outbreaks. Decontamination strategies that are user- and environmentally-friendly without toxic by-product formation are needed. Novel UV-C light-emitting diode (LED) technologies are being explored to deliver the required dose to inactivate viruses in food-processing environments. The objective of this study was to compare the effects of 279 nm UV-C LED to 254 nm UV-C against hepatitis A virus (HAV) and feline calicivirus (FCV, a cultivable human norovirus surrogate) on stainless-steel, ceramic, and glass surfaces. Viruses were surface spread on sterile stainless-steel or ceramic coupons (100 μL on 2 × 2 cm2), or glass discs (50 μL on 1 × 1 cm2), air-dried, and UV-C-treated for up to 3.75 min (surface dose = 0-49.2 mJ/cm2 for HAV and 0-24.6 mJ/cm2 for FCV). Each triplicate treatment was assayed in duplicate, and data were statistically analyzed. The D10-values for HAV treated with UV-C at 254 nm on stainless-steel, ceramic, and glass were 9.48 ± 0.34, 14.53 ± 2.52, and 6.91 ± 1.93 mJ/cm2, while with UV-C LED at 279 nm were 19.53 ± 2.45, 26.05 ± 0.60, and 8.77 ± 2.08 mJ/cm2, respectively. The D10-values for FCV treated with UV-C at 254 nm on stainless-steel, ceramic, and glass were 3.65 ± 0.06, 6.25 ± 1.90, and 4.69 ± 0.03 mJ/cm2, while with UV-C LED at 279 nm were 7.097 ± 2.11, 8.31 ± 2.12, and 7.88 ± 0.86 mJ/cm2, respectively. Higher 279 nm UV-C doses were needed to inactivate HAV and FCV compared to 254 nm UV-C on the tested surfaces. Novel UV-C LED systems using appropriate doses show promise to inactivate foodborne viruses on food contact surfaces.

Imaging-Based Drug Penetration Profiling in an Excised Sheep Cornea Model.

Formulations designed to address ocular conditions and diseases are predominantly administered topically. While in vitro test systems have been developed to assess corneal permeation under extended contact conditions, methods focusing on determining the penetration depth and kinetics of a substance within the cornea itself rather than through it, are scarce. This study introduces a method for time-dependent penetration depth analysis (10 and 60 min) by means of a semiquantitative imaging method in comparison with a quantitative corneal depth-cut technique, employing fluorescein sodium at concentrations of 0.2 and 0.4 mg/mL as a small molecule model substance and sheep cornea as a human surrogate. Excised tissues exhibited sustained viability in modified artificial aqueous humor and maintained thickness (746 ± 43 µm) and integrity (electrical resistance 488 ± 218 Ω∙cm2) under the experimental conditions. Both methods effectively demonstrated the expected concentration- and time-dependent depth of penetration of fluorescein sodium, displaying a significantly strong correlation. The traceability of the kinetic processes was validated with polysorbate 80, which acted as a penetration enhancer. Furthermore, the imaging-based method enabled detecting the retention of larger structures, such as hyaluronic acid and nanoemulsions from the commercial eyedrop formulation NEOVIS® TOTAL multi, inside the lacrimal layer.

Utilizing Zebrafish Embryos for Replication of Tulane Virus: A Human Norovirus Surrogate

The zebrafish larvae/embryo model has been shown to support the replication of seven strains (G1.7[P7], GII.2[P16], GII.3[P16], GII.4[P4], GII.4[P16], GII.6[P7], and GII.17[P13]) of human norovirus (HuNoV). However, due to challenges in consistently obtaining HuNoV-positive stool samples from clinical sources, evaluating HuNoV surrogates in this model is highly valuable. This study assesses the potential of zebrafish embryos and larvae as a model for Tulane virus (TuV) replication. Three infection methods were examined: microinjection, immersion, and feeding. Droplet digital PCR was used to quantify viral RNA across all three infection methods. Microinjection of 3 nL of TuV into zebrafish embryos (< 6-h post-fertilization) resulted in significant replication, with viral RNA levels reaching 6.22 logs at 4-day post-infection. In contrast, the immersion method showed no replication after immersing 4-day post-fertilization (dpf) larvae in TuV suspension for 6 h. Similarly, no replication was observed with the feeding method, where Paramecium caudatum loaded with TuV were fed to 4 dpf larvae. The findings indicate that the zebrafish embryo model supports TuV replication through the microinjection method, suggesting that TuV may serve as a useful surrogate for studying HuNoV pathogenesis. Additionally, TuV can be utilized in place of HuNoV in method optimization studies using the zebrafish embryo model, circumventing the limited availability of HuNoV.

Anatomical Features and Material Properties of Human Surrogate Head Models Affect Spatial and Temporal Brain Motion under Blunt Impact.

Traumatic brain injury (TBI) is a biomechanical problem where the initiating event is dynamic loading (blunt, inertial, blast) to the head. To understand the relationship between the mechanical parameters of the injury and the deformation patterns in the brain, we have previously developed a surrogate head (SH) model capable of measuring spatial and temporal deformation in a surrogate brain under blunt impact. The objective of this work was to examine how material properties and anatomical features affect the motion of the brain and the development of injurious deformations. The SH head model was modified to study six variables independently under blunt impact: surrogate brain stiffness, surrogate skull stiffness, inclusion of cerebrospinal fluid (CSF), head/skull size, inclusion of vasculature, and neck stiffness. Each experimental SH was either crown or frontally impacted at 1.3 m/s (3 mph) using a drop tower system. Surrogate brain material, the Hybrid III neck stiffness, and skull stiffness were measured and compared to published properties. Results show that the most significant variables affecting changes in brain deformation are skull stiffness, inclusion of CSF and surrogate brain stiffness. Interestingly, neck stiffness and SH size significantly affected the strain rate only suggesting these parameters are less important in blunt trauma. While the inclusion of vasculature locally created strain concentrations at the interface of the artery and brain, overall deformation was reduced.

Efficacy of three EPA-registered antimicrobials and steam against two human norovirus surrogates on nylon carpets with two backing types.

Carpet cleaning guidelines currently do not include the use of an antimicrobial, except after a bodily fluid event. To address this gap, we compared the efficacy of three antimicrobials-two hydrogen peroxide-based (H2O2) products (A and B) and one chlorine-based product (C)-and a steam treatment against two norovirus surrogates, specifically feline calicivirus (FCV) and Tulane virus (TuV). These tests were performed on nylon carpets with either water-permeable or waterproof backing types. The effect of repeated antimicrobial use on carpet properties was also evaluated. For a carpet with water-permeable backing, products A, B, and C achieved a 0.8, 3.1, and 0.9 log10 PFU/coupon reduction of FCV and 0.3, 2.5, and 0.4 log10 TCID50/coupon reduction of TuV, respectively, following a 30 min contact time. For carpet with waterproof backing, only product B achieved a 5.0 log10 PFU/coupon reduction of FCV and >3.0 log10 TCID50/coupon reduction of TuV, whereas products A and C achieved a 2.4 and 1.6 log10 PFU/coupon reduction of FCV and a 1.2 and 1.2 log10 TCID50/coupon reduction of TuV, respectively. Steam treatment achieved a ≥ 5.2 log10 PFU/coupon reduction of FCV and a > 3.2 log10 TCID50/coupon reduction of TuV in 15 seconds on the carpet with both backing types. The repeated use of products A and B decreased the tensile strength of the carpet backing, while use of product B resulted in cracks on carpet fibers. Overall, steam treatment for 15 seconds was efficacious on both carpet types, but only product B achieved efficacy after a 30-minute exposure on the carpet with waterproof backing.IMPORTANCECarpets are common in long-term care facilities, despite its potential as a vehicle for transmission of agents associated with healthcare-associated infections, including human norovirus (NoV). Presently, our understanding of carpet disinfection is limited; hence, there are no commercial antimicrobials against norovirus available for use on carpets. Our findings showed that steam treatment, which minimally affected the properties of carpet fibers and backing, was more efficacious against human norovirus surrogates on carpets compared to the three chemical antimicrobials tested. Additionally, the two surrogates were more sensitive to chemical antimicrobials on the carpet with waterproof backing compared to carpets with water-permeable backing. These findings can inform development of antimicrobials for use on carpets contaminated with human norovirus.

Evaluating the Potential of Ozone Microbubbles for Inactivation of Tulane Virus, a Human Norovirus Surrogate

Evaluating the Potential of Ozone Microbubbles for Inactivation of Tulane Virus, a Human Norovirus Surrogate

Survival modelling of infectious human norovirus and surrogates for high-pressure inactivation in strawberry puree

Berries contaminated with human norovirus (HuNoV) have been frequently identified as a cause of foodborne gastroenteritis. To prevent virus transmission while preserving sensory and quality parameters, non-thermal treatments, such as high-pressure processing (HPP), can be applied to the berries and products thereof. Here, strawberry purees contaminated with HuNoV genogroup I (GI.3[P13]) and II (GII.4 Sydney [P16]), along with murine norovirus (MNV) and Tulane virus (TV) serving as surrogates, were exposed to HPP at several pressure-time combinations. Virus inactivation was assessed by cell culture, including the novel human intestinal enteroids (HIE) model for HuNoVs. The infectivity results showed TV more resistant than MNV to HPP, as also confirmed by kinetic mathematical modelling. Results indicated that a holding pressure of 450 MPa and an exposure time of ≥5 min are reliable operational conditions for HPP process to successfully control viral contamination. In addition, the inactivation models deduced from MNV and TV viruses were challenged with experimental HuNoV GII.4 infectivity resulting in bias factors <1 for all treatment conditions. This finding validates the proposed models for the conservative estimation of HuNoV inactivation. Our work offers a blueprint for moving forward with inactivation studies using the HIE system, which provides useful practical information on optimum treatments for the best public health outcomes.

Tulane Virus Persistence and Microbial Stability in 3D Food Ink under Various Storage Conditions: A Pre- and Post-Printing Analysis

3D food printers facilitate novel customization of the physicochemical properties of food. This study aimed to investigate the impact of storage conditions on the inactivation of the human norovirus surrogate, Tulane virus (TuV), within 3D printed foods. TuV-inoculated protein cookie food ink (∽ 4 log PFU/g) was distributed into 18 3D food printer capsules (50 g each); half immediately underwent extrusion. Storage of the capsules and printed food products at 20 °C (0, 6, 12, and 24 h), 4 °C (0, 1, 3, and 5d), and − 18 °C (0, 1, 3, and 5d) was completed before analysis for TuV via plaque assays in addition to aerobic plate count, yeast and mold counts, and pH and water activity (aw) measurements. A significant 3-way interaction effect was observed between time, temperature, and storage method (capsule/print) (p = 0.006). Significant findings include: (1) A greater reduction in virions was observed in capsules after 24 h at 20 °C and (2) a substantial reduction in virions at 4 °C from day 0 to day 1 was observed, independent of storage method. Microbial indicators remained steady across temperatures, with storage temperature significantly impacting pH and aw. A significant two-way interaction effect (p = 0.006) was found between microorganism type (yeast/aerobic counts) and temperature. This research seeks to provide insights for the food industry and regulatory bodies in crafting guidelines for the safe storage and handling of 3D printed foods and inks.

Comparison of Adult Female and Male PMHS Pelvis and Lumbar Response to Underbody Blast.

The goal of this study was to gather and compare kinematic response and injury data on both female and male whole-body Post-mortem Human Surrogates (PMHS) responses to Underbody Blast (UBB) loading. Midsized males (50th percentile, MM) have historically been most used in biomechanical testing and were the focus of the Warrior Injury Assessment Manikin (WIAMan) program, thus this population subgroup was selected to be the baseline for female comparison. Both small female (5th percentile, SF) and large female (75th percentile, LF) PMHS were included in the test series to attempt to discern whether differences between male and female responses were predominantly driven by sex or size. Eleven tests, using 20 whole-body PMHS, were conducted by the research team. Preparation of the rig and execution of the tests took place at the Aberdeen Proving Grounds (APG) in Aberdeen, MD. Two PMHS were used in each test. The Accelerative Loading Fixture (ALF) version 2, located at APG's Bear Point range was used for all male and female whole-body tests in this series. The ALF was an outdoor test rig that was driven by a buried explosive charge, to accelerate a platform holding two symmetrically mounted seats. The platform was designed as a large, rigid frame with a deformable center section that could be tuned to simulate the floor deformation of a vehicle during a UBB event. PMHS were restrained with a 5-point harness, common in military vehicle seats. Six-degree-of-freedom motion blocks were fixed to L3, the sacrum, and the left and right iliac wings. A three-degree-of freedom block was fixed to T12. Strain gages were placed on L4 and multiple locations on the pelvis. Accelerometers on the floor and seat of the ALF provided input data for each PMHS' feet and pelvis. Time histories and mean peak responses in z-axis acceleration were similar among the three PMHS groups in this body region. Injury outcomes were different and seemed to be influenced by both sex and size contributions. Small females incurred pelvis injuries in absence of lumbar injures. Midsized males had lumbar vertebral body fractures without pelvis injuries. And large females with injuries had both pelvis and lumbar VB fractures. This study provides evidence supporting the need for female biomechanical testing to generate female response and injury thresholds. Without the inclusion of female PMHS, the differences in the injury patterns between the small female and midsized male groups would not have been recognized. Standard scaling methods assume equivalent injury patterns between the experimental and scaled data. In this study, small female damage occurred in a different anatomical structure than for the midsized males. This is an important discovery for the development of anthropomorphic test devices, injury criteria, and injury mitigating technologies. The clear separation of small female damage results, in combination with seat speeds, suggest that the small female pelvis injury threshold in UBB events lies between 4 - 5 m/s seat speed. No inference can be made about the small female lumbar threshold, other than it is likely at higher speeds and/or over longer duration. Male lumbar spine damage occurred in both the higher- and lower lower-rate tests, indicating the injury threshold would be below the seat pulses tested in these experiments. Large females exhibited injury patterns that reflected both the small female and midsized male groups - with damaged PMHS having fractures in both pelvis and lumbar, and in both higher- and lower- rate tests. The difference in damage patterns between the sex and size groups should be considered in the development of injury mitigation strategies to protect across the full population.

Frontal-Crash Occupant Protection in the Rear Seat: Submarining and Abdomen/Pelvis Response in Midsized Male Surrogates.

Frontal-crash sled tests were conducted to assess submarining protection and abdominal injury risk for midsized male occupants in the rear seat of modern vehicles. Twelve sled tests were conducted in four rear-seat vehicle-bucks with twelve post-mortem human surrogates (PMHS). Select kinematic responses and submarining incidence were compared to previously observed performance of the Hybrid III 50th-percentile male and THOR-50M ATDs (Anthropomorphic Test Devices) in matched sled tests conducted as part of a previous study. Abdominal pressure was measured in the PMHS near each ASIS (Anterior Superior Iliac Spine), in the inferior vena cava, and in the abdominal aorta. Damage to the abdomen, pelvis, and lumbar spine of the PMHS was also identified. In total, five PMHS underwent submarining. Four PMHS, none of which submarined, sustained pelvis fractures and represented the heaviest of the PMHS tested. Submarining of the PMHS occurred in two out of four vehicles. In the matched tests, the Hybrid III never underwent submarining while the THOR-50M submarined in three out of four vehicles. Submarining occurred in vehicles having both conventional and advanced (pretensioner and load limiter) restraints. The dominant factors associated with submarining were related to seat pan geometry. While the THOR-50M was not always an accurate tool for predicting submarining in the PMHS, the Hybrid III could not predict submarining at all. The results of this study identify substantive gaps in frontal-crash occupant protection in the rear seat for midsized males and elucidates the need for additional research for rear-seat occupant protection for all occupants.

Human Norovirus Surrogate Is Highly Stable in Berry Smoothies and under In Vitro Simulated Digestion.

Human noroviruses are major causes of foodborne outbreaks linked to berries. The overall goal of this study was to investigate the persistence of a human norovirus surrogate, Tulane virus (TV), in berry smoothies and under simulated digestion through the gastrointestinal track. Two types of smoothies were prepared from blueberries and strawberries. Tulane virus was spiked into each smoothie and incubated either at 37 or 4 °C for 2, 60, and 120 min. Furthermore, the virus-spiked smoothies were subjected to sequential oral (2 min), gastric (10 and 60 min), and intestinal (15 and 120 min) digestion according to the standardized INFOGEST model. Quantification of infectious TV was carried out using the TCID50 assay. At 4 °C, in both berry smoothies, TV infectivity did not show significant changes throughout the 120 min period. At 37 °C, TV infectivity showed significant reduction (~0.5 log TCID50/mL) only in blueberry smoothies starting at 60 min. During the oral, gastric, and intestinal digestion phases, the mean log reduction in TV infectivity in blueberry did not exceed ~0.5 log, while infectious TV in strawberry smoothies under all phases was stable. Given the notable stability of infectious viruses in berry smoothies and the gastrointestinal tract, prevention of norovirus contamination of berries is paramount to reduce virus outbreaks linked to berries.

Review of non-penetrating ballistic testing techniques for protection assessment: From biological data to numerical and physical surrogates.

Human surrogates have long been employed to simulate human behaviour, beginning in the automotive industry and now widely used throughout the safety framework to estimate human injury during and after accidents and impacts. In the specific context of blunt ballistics, various methods have been developed to investigate wound injuries, including tissue simulants such as clays or gelatine ballistic, physical dummies and numerical models. However, all of these surrogate entities must be biofidelic, meaning they must accurately represent the biological properties of the human body. This paper provides an overview of physical and numerical surrogates developed specifically for blunt ballistic impacts, including their properties, use and applications. The focus is on their ability to accurately represent the human body in the context of blunt ballistic impact.

Hydroponic Nutrient Solution Temperature Impacts Tulane Virus Persistence over Time

Controlled environment agriculture (CEA), or indoor agriculture, encompasses non-traditional farming methods that occur inside climate-controlled structures (e.g., greenhouses, warehouses, high tunnels) allowing for year-round production of fresh produce such as leaf lettuce. However, recent outbreaks and recalls associated with hydroponically grown lettuce contaminated with human pathogens have raised concerns. Few studies exist on the food safety risks during hydroponic cultivation of leaf lettuce; thus, it is important to identify contributing risk factors and potential mitigation strategies to prevent foodborne transmission via hydroponically grown produce. In this study, the concentration of infectious Tulane virus (TV), a human norovirus surrogate, in hydroponic nutrient solution at 15 °C, 25 °C, 30 °C, and 37 °C was determined over a duration of 21 days to mimic the time from seedling to mature lettuce. The mean log PFU reduction for TV was 0.86, 1.80, 2.87, and ≥ 3.77 log10 at 15 °C, 25 °C, 30 °C, and 37 °C, respectively, at the end of the 21-day period. Similarly, average decimal reduction values (D-values) of TV at 15 °C, 25 °C, 30 °C, and 37 °C were 48.0, 11.3, 8.57, and 7.02 days, respectively. This study aids in the (i) identification of possible food safety risks associated with hydroponic systems specifically related to nutrient solution temperature and (ii) generation of data to perform risk assessments within CEA leaf lettuce operations to inform risk management strategies for the reduction of foodborne outbreaks, fresh produce recalls, and economic losses.

A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis.

Introduction: Understanding drug exposure at disease target sites is pivotal to profiling new drug candidates in terms of tolerability and efficacy. Such quantification is particularly tedious for anti-tuberculosis (TB) compounds as the heterogeneous pulmonary microenvironment due to the infection may alter lung permeability and affect drug disposition. Murine models have been a longstanding support in TB research so far and are here used as human surrogates to unveil the distribution of several anti-TB compounds at the site-of-action via a novel and centralized PBPK design framework. Methods: As an intermediate approach between data-driven pharmacokinetic (PK) models and whole-body physiologically based (PB) PK models, we propose a parsimonious framework for PK investigation (minimal PBPK approach) that retains key physiological processes involved in TB disease, while reducing computational costs and prior knowledge requirements. By lumping together pulmonary TB-unessential organs, our minimal PBPK model counts 9 equations compared to the 36 of published full models, accelerating the simulation more than 3-folds in Matlab 2022b. Results: The model has been successfully tested and validated against 11 anti-TB compounds-rifampicin, rifapentine, pyrazinamide, ethambutol, isoniazid, moxifloxacin, delamanid, pretomanid, bedaquiline, OPC-167832, GSK2556286 - showing robust predictability power in recapitulating PK dynamics in mice. Structural inspections on the proposed design have ensured global identifiability and listed free fraction in plasma and blood-to-plasma ratio as top sensitive parameters for PK metrics. The platform-oriented implementation allows fast comparison of the compounds in terms of exposure and target attainment. Discrepancies in plasma and lung levels for the latest BPaMZ and HPMZ regimens have been analyzed in terms of their impact on preclinical experiment design and on PK/PD indices. Conclusion: The framework we developed requires limited drug- and species-specific information to reconstruct accurate PK dynamics, delivering a unified viewpoint on anti-TB drug distribution at the site-of-action and a flexible fit-for-purpose tool to accelerate model-informed drug design pipelines and facilitate translation into the clinic.

Electroless silver plating on fabrics for antimicrobial coating: comparison between cotton and polyester.

In the past few years, due to the Covid-19 pandemic, the interest towards textiles with antimicrobial functionalities faced a significant boost. This study proposes a rapid and convenient method, in terms of reactants and equipment, for fabricating antimicrobial coatings on textiles. Through the electroless silver plating reaction, silver coatings were successfully applied on cotton and polyester, rapidly and at room temperature. Functionalized samples were characterized by morphological (optical and scanning electron microscopies) and chemical tests (X-ray photoelectron spectroscopy, XPS) to investigate the nature of the silver coating. Although distinct nanoparticles did not form, XPS analysis detected the presence of silver, which resulted in an increased surface roughness and hydrophobicity of both cotton and polyester textiles. Ag-coated samples exhibited approximately 80% biocompatibility with murine L929 fibroblasts or human HaCaT cells, and strong antibacterial properties against Escherichia coli in direct contact tests. In antiviral experiments with SARS-CoV-2 virus, treated cotton showed a 100% viral reduction in 30 min, while polyester achieved 100% reduction in 1 h. With a human norovirus surrogate, the Feline Calicivirus, both treated textiles have a faster antiviral response, with more than 60% viral reduction after 5 min, while achieving a 100% reduction in 1 h. In conclusion, this study presents a fast, efficient, and low-cost solution for producing antimicrobial textiles with broad applications in medical and healthcare scenarios.