Monitoring redox stress in human airway epithelial cells exposed to woodsmoke at an air-liquid interface.

Wildland fires contribute significantly to the ambient air pollution burden worldwide, causing a range of adverse health effects in exposed populations. The toxicity of woodsmoke, a complex mixture of gases, volatile organic compounds, and particulate matter, is commonly studied in vitro using isolated exposures of conventionally cultured lung cells to either resuspended particulate matter or organic solvent extracts of smoke, leading to incomplete toxicity evaluations. This study aimed to improve our understanding of the effects of woodsmoke inhalation by building an advanced in vitro exposure system that emulates human exposure of the airway epithelium. We report the development and characterization of an innovative system that permits live-cell monitoring of the intracellular redox status of differentiated primary human bronchial epithelial cells cultured at an air-liquid interface (pHBEC-ALI) as they are exposed to unfractionated woodsmoke generated in a tube furnace in real time. pHBEC-ALI exposed to freshly generated woodsmoke showed oxidative changes that were dose-dependent and reversible, and not attributable to carbon monoxide exposure. These findings show the utility of this novel system for studying the molecular initiating events underlying woodsmoke-induced toxicity in a physiologically relevant in vitro model, and its potential to provide biological plausibility for risk assessment and public health measures.

Displacement Estimation via 3D-Printed RFID Sensors for Structural Health Monitoring: Leveraging Machine Learning and Photoluminescence to Overcome Data Gaps.

Monitoring object displacement is critical for structural health monitoring (SHM). Radio frequency identification (RFID) sensors can be used for this purpose. Using more sensors enhances displacement estimation accuracy, especially when it is realized through the use of machine learning (ML) algorithms for predicting the direction of arrival of the associated signals. Our research shows that ML algorithms, in conjunction with adequate RFID passive sensor data, can precisely evaluate azimuth angles. However, increasing the number of sensors can lead to gaps in the data, which typical numerical methods such as interpolation and imputation may not fully resolve. To overcome this challenge, we propose enhancing the sensitivity of 3D-printed passive RFID sensor arrays using a novel photoluminescence-based RF signal enhancement technique. This can boost received RF signal levels by 2 dB to 8 dB, depending on the propagation mode (near-field or far-field). Hence, it effectively mitigates the issue of missing data without necessitating changes in transmit power levels or the number of sensors. This approach, which enables remote shaping of radiation patterns via light, can herald new prospects in the development of smart antennas for various applications apart from SHM, such as biomedicine and aerospace.

Displacement Estimation Using 3D-Printed RFID Arrays for Structural Health Monitoring.

Radio frequency identification (RFID) tags are small, low-cost, wearable, and wireless sensors that can detect movement in structures, humans, or robots. In this paper, we use passive RFID tags for structural health monitoring by detecting displacements. We employ a novel process of using 3D printable embedded passive RFID tags within uniform linear arrays together with the multiple signal classification algorithm to estimate the direction of arrival using only the phase of the backscattered signals. We validate our proposed approach via data collected from real-world experiments using a unipolar RFID reader antenna and both narrowband and wideband measurements.

Advancements in Therapeutics via 3D Printed Multifunctional Architectures from Dispersed 2D Nanomaterial Inks.

2D nanomaterials (2DNMs) possess fascinating properties and are found in multifarious devices and applications including energy storage devices, new generation of battery technologies, sensor devices, and more recently in biomedical applications. Their use in biomedical applications such as tissue engineering, photothermal therapy, neural regeneration, and drug delivery has opened new horizons in treatment of age-old ailments. It is also a rapidly developing area of advanced research. A new approach of integrating 3D printing (3DP), a layer-by-layer deposition technique for building structures, along with 2DNM multifunctional inks, has gained considerable attention in recent times, especially in biomedical applications. With the ever-growing demand in healthcare industry for novel, efficient, and rapid technologies for therapeutic treatment methods, 3DP structures of 2DNMs provide vast scope for evolution of a new generation of biomedical devices. Recent advances in 3DP structures of dispersed 2DNM inks with established high-performance biomedical properties are focused on. The advantages of their 3D structures, the sustainable formulation methods of such inks, and their feasible printing methods are also covered. Subsequently, it deals with the therapeutic applications of some already researched 3DP structures of 2DNMs and concludes with highlighting the challenges as well as the future directions of research in this area.

In vivo study to compare the effects of Choline with Fluoxetine and Clozapine for the modulation of cognitive behavior (Learning Memory and Exploratory Behavior).

Cognitive behavior is associated with physiological processes that affect the working performance of an individual. Cognitive control is used to override self-serving impulses and behave in socially desirable manner. The objective of the study is to compare the effects of Choline with Fluoxetine and Clozapine for the modulation of cognitive behavior including learning, memory, locomotor, exploratory behavior and anxiety. The study was based on twenty four albino rats divided into four equal groups: (1) Control kept on normal saline (2) Fluoxetine (3) Clozapine (4) Choline. Morris Water Maze (WM) test was used for the psychological assessment based on neural mechanism involved in spatial learning and memory. Open field activity test evaluated locomotor and exploratory behavior. The behavior modulation in WM test and open field activity test was determined at 1st, 3rd, 5th and 7th week. Fluoxetine, Clozapine and Choline were used as drugs and administered to the rat groups mentioned earlier. The modulation of behavior in WM test and Open field activity test was recorded at 1st, 3rd, 5th and 7th week after administering the drugs. Impairment in learning behavior in Fluoxetine treated group was observed at 1st, 3rd, 5th and 7th week and in Clozapine group at 1st and 2nd week when compared to Control (Saline) group. Rise in latency time was observed in Fluoxetine treated group but was not significant. Clozapine and Choline had exhibited beneficial effects in memory retention and prevention of learning impairment. The findings have led to the conclusion that Choline and Clozapine improve the memory retention after continuous administration of 5 and 7 weeks. Moreover, Clozapine has different receptor specificity as compared to Choline. However, both improve the learning capability and enhance the memory in rats. Meanwhile, Fluoxetine did not show any considerable enhancement of memory.

Under-recognition of Low Blood Pressure Readings in Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD), a recessive sex-linked hereditary disorder, is characterized by degeneration, atrophy, and weakness of skeletal and cardiac muscle. The purpose of this study was to document the prevalence of abnormally low resting BP recordings in patients with DMD in our outpatient clinic. The charts of 31 patients with DMD attending the cardiology clinic at Rush University Medical Center were retrospectively reviewed. Demographic data, systolic, diastolic, and mean blood pressures along with current medications, echocardiograms, and documented clinical appreciation and management of low blood pressure were recorded in the form of 104 outpatient clinical visits. Blood pressure (BP) was classified as low if the systolic and/or mean BP was less than the fifth percentile for height for patients aged ≤17 years (n = 23). For patients ≥18 years (n = 8), systolic blood pressure (SBP) <90 mmHg or a mean arterial pressure (MAP) <60 mmHg was recorded as a low reading. Patients with other forms of myopathy or unclear diagnosis were excluded. Statistical analysis was done using PASW version 18. BP was documented at 103 (99.01 %) outpatient encounters. Low systolic and mean BP were recorded in 35 (33.7 %) encounters. This represented low recordings for 19 (61.3 %) out of a total 31 patients with two or more successive low recordings for 12 (38.7 %) patients. Thirty-one low BP encounters were in patients <18 years old. Hispanic patients accounted for 74 (71.2 %) visits and had low BP recorded in 32 (43.2 %) instances. The patients were non-ambulant in 71 (68.3 %) encounters. Out of 35 encounters with low BP, 17 patients (48.6 %) were taking heart failure medication. In instances when patients had low BP, 22 (66.7 %) out of 33 echocardiography encounters had normal left ventricular ejection fraction. Clinician comments on low BP reading were present in 11 (10.6 %) encounters, and treatment modification occurred in only 1 (1 %) patient. Age in years (p = .031) and ethnicity (p = .035) were independent predictors of low BP using stepwise multiple regression analysis. Low BP was recorded in a significant number of patient encounters in patients with DMD. Age 17 years or less and Hispanic ethnicity were significant predictors associated with low BP readings in our DMD cohort. Concomitant heart failure therapy was not a statistically significant association. There is a need for enhanced awareness of low BP in DMD patients among primary care and specialty physicians. The etiology and clinical impact of these findings are unclear but may impact escalation of heart failure therapy.

The use of intracardiac echocardiography during percutaneous pulmonary valve replacement.

High-quality live imaging assessment of cardiac valves and cardiac anatomy is crucial for the success of catheter-based procedures. We present our experience using Intracardiac echocardiography (ICE) during transcatheter Percutaneous Pulmonary Valve replacement (tPVR).This is a retrospective study that included 35 patients who underwent tPVR between April 2008 and June 2012. Thirty-one of these patients had the procedure performed under continuous ICE guidance. Pre-procedure transthoracic echocardiography (TTE) was obtained in all patients. ICE was performed at baseline, during the procedure, and at the conclusion of the procedure. Comparisons between the pre-procedure TTE and baseline ICE data and between post-procedure ICE data and the following day TTE were performed. Total of 35 patients had tPVR during the above-mentioned time period. Twenty-one patients received the Edwards Sapien valve and 14 patients had the Melody valve. Thirty-one patients had the procedure performed under continuous ICE guidance. The mean Pre-TTE peak gradient (PG) and Pre-ICE-PG were 45.5 ± 20 vs 33 ± 13 mmHg (p < 0.001) and the mean Pre-TTE mean gradient (MG) and Pre-ICE-MG were 27.7 ± 13 vs 21 ± 18 mmHg (p < 0.001). The mean Post-TTE- PG and Post-ICE-PG were 24.3 ± 11 vs 15.3 ± 7 mmHg (p < 0.001) and the mean of the Post-TTE-MG and Post-ICE-MG were 14.2 ± 7 vs 8.4 ± 4 mmHg (p < 0.001). There was a good correlation between peak ICE and TTE gradient at baseline and after valve placement. For the degree of pulmonary regurgitation, there was no significant difference between TTE and ICE. ICE is an important modality to guide tPVR in patients with dysfunctional homograft valve between the right ventricle and pulmonary artery and should be used to assess valve function before, during and immediately after the procedure.

Anomalies Unveiled: A Fascinating Case Study of Type I Pulmonary Artery-to-Left Atrium Fistula.

The pulmonary artery-to-left atrium (LA) fistula is one of the rare and unique structural causes of silent cyanosis. This correctable abnormality can be identified by having a high index of clinical suspicion and appropriate investigations using echocardiography and cardiac computed tomography (CT). We report an eight-year-old child who had worsening exertional dyspnea, long-standing central cyanosis, and recurrent infections. A large-sized fistula connecting the right pulmonary artery (RPA) to the LA with all the right- and left-sided pulmonary veins showed normal drainage into the LA, suggesting a type I RPA-to-LA fistula, which was diagnosed on cardiac CT. Percutaneous closure using the occluder device is planned as further management for the patient.

Comparison of permeable cell culture inserts for use in culture of a human in vitro air-liquid interface model system.

In this study, we compared 12 mm cell culture inserts with permeable polyester membranes (0.4 µm pores) from two different manufacturers: CELLTREAT® and Corning®. Physical dimensions and masses of the inserts were found to be very similar between the two brands, with CELLTREAT® inserts having a slightly smaller diameter and growth area (11.91 mm; 1.11 cm2 ) compared to Corning® Transwells® (12 mm; 1.13 cm2 ). We compared cell differentiation outcomes of human nasal epithelial cells (HNECs) at air-liquid interface grown on inserts from the two different manufacturers, including trans-epithelial electrical resistance, ciliary beat frequency, ciliated area, and gene expression. HNECs from three male donors were used for all endpoints. No statistically significant differences were observed between paired cultures grown on different brands of insert. In conclusion, these inserts are comparable for use with airway epithelial cell model systems and likely do not impact cellular differentiation or cell culture quality.

Emissions from plastic incineration induce inflammation, oxidative stress, and impaired bioenergetics in primary human respiratory epithelial cells.

Inhalation exposure to plastic incineration emissions (PIEs) is a problem of increasing human relevance, as plastic production and waste creation have drastically increased since mainstream integration during the 20th century. We investigated the effects of PIEs on human nasal epithelial cells (HNECs) to understand if such exposures cause damage and dysfunction to respiratory epithelia. Primary HNECs from male and female donors were cultured at air-liquid interface (ALI), and 16HBE cells were cultured on coverslips. Smoke condensates were generated from incineration of plastic at flaming (640°C) and smoldering (500°C) temperatures, and cells were subsequently exposed to these materials at 5-50 µg/cm2 concentrations. HNECs were assessed for mitochondrial dysfunction and 16HBE cells for glutathione oxidation in real-time analyses. HNEC culture supernatants and total RNA were collected at 4-h postexposure for cytokine and gene expression analysis, and results show that PIEs can acutely induce inflammation, oxidative stress, and mitochondrial dysfunction in HNECs, and that incineration temperature modifies biological responses. Specifically, condensates from flaming and smoldering PIEs significantly increased HNEC secretion of cytokines IL-8, IL-1ß, and IL-13, as well as expression of xenobiotic metabolism pathways and genes such as CYP1A1 and CYP1B1 at 5 and 20 µg/cm2 concentrations. Only 50 µg/cm2 flaming PIEs significantly increased glutathione oxidation in 16HBEs, and decreased respiration and ATP production in HNEC mitochondria. Impact Statement: Our data reveal the impact of incineration temperatures on biological outcomes associated with PIE exposures, emphasizing the importance of temperature as a factor when evaluating respiratory disease associated with PIEs exposure.

GAPDH inhibition mediated by thiol oxidation in human airway epithelial cells exposed to an environmental peroxide.

Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to xenobiotic stressors such as secondary organic aerosols (SOA) can alter intracellular redox homeostasis. Isoprene hydroxy hydroperoxide (ISOPOOH), a ubiquitous volatile organic compound derived from the atmospheric photooxidation of biogenic isoprene, is a major contributor to SOA. We have previously demonstrated that exposure of human airway epithelial cells (HAEC) to ISOPOOH induces oxidative stress through multiple mechanisms including lipid peroxidation, glutathione oxidation, and alterations of glycolytic metabolism. Using dimedone-based reagents and copper catalyzed azo-alkynyl cycloaddition to tag intracellular protein thiol oxidation, we demonstrate that exposure of HAEC to micromolar levels of ISOPOOH induces reversible oxidation of cysteinyl thiols in multiple intracellular proteins, including GAPDH, that was accompanied by a dose-dependent loss of GAPDH enzymatic activity. These results demonstrate that ISOPOOH induces an oxidative modification of intracellular proteins that results in loss of GAPDH activity, which ultimately impacts the dynamic regulation of the intracellular redox homeostatic landscape in HAEC.

Till debt does us apart: Cross-country evidence on the relationship between microfinance prevalence and social distrust.

Economic interventions have social consequences. In this paper, we explore one such relationship, between microfinance intensity and social distrust levels reported by the low-income people. We find a significant association between microfinance intensity in a country and distrust among the poor as well as ultra-poor in cross-section using World Values Survey & European Values Survey (WVS-EVS) Wave 7 (2017-2022). We supplement these findings using empirical Bayes on a panel extending back from 7th to the 4th WVS wave (1999-2004). To deal with potential endogeneity, we run 2SLS as well as weak instruments-robust conditional instrumental variable tests and find evidence showing microfinance prevalence intensity affects distrust levels among the poor and ultra-poor households. We find no association between microfinance and distrust levels in the rich in any of the tests, potentially because the rich are not exposed to microfinance.

Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis.

Exposure to ozone (O3) is associated with adverse respiratory and cardiovascular outcomes. Alterations in circulating microRNAs (miRNAs) may contribute to the adverse vascular effects of O3 exposure through inter-cellular communication resulting in post-transcriptional regulation of messenger RNAs by miRNAs. In this study, we investigated whether O3 exposure induces alterations in circulating miRNAs that can mediate effects on downstream vascular and coagulation biomarkers. Twenty-three healthy male adults were exposed on successive days to filtered air and 300 ppb O3 for 2 h. Circulating miRNA and protein biomarkers were quantified after each exposure session. The data were subjected to mixed-effects model and mediation analyses for the statistical analyses. The results showed that the expression level of multiple circulating miRNAs (e.g., miR-19a-3p, miR-34a-5p) was significantly associated with O3 exposure. Pathway analysis showed that these miRNAs were predictive of changing levels of downstream biomarkers [e.g., D-dimer, C-reactive protein, tumor necrosis factor α (TNFα)]. Mediation analysis showed that miR-19a-3p may be a significant mediator of O3-exposure-induced changes in blood TNFα levels [0.08 (0.01, 0.15), p = 0.02]. In conclusion, this preliminary study showed that O3 exposure of healthy male adults resulted in changes in circulating miRNAs, some of which may mediate vascular effects of O3 exposure.

Real-time redox adaptations in human airway epithelial cells exposed to isoprene hydroxy hydroperoxide.

While redox processes play a vital role in maintaining intracellular homeostasis by regulating critical signaling and metabolic pathways, supra-physiological or sustained oxidative stress can lead to adverse responses or cytotoxicity. Inhalation of ambient air pollutants such as particulate matter and secondary organic aerosols (SOA) induces oxidative stress in the respiratory tract through mechanisms that remain poorly understood. We investigated the effect of isoprene hydroxy hydroperoxide (ISOPOOH), an atmospheric oxidation product of vegetation-derived isoprene and a constituent of SOA, on intracellular redox homeostasis in cultured human airway epithelial cells (HAEC). We used high-resolution live cell imaging of HAEC expressing the genetically encoded ratiometric biosensors Grx1-roGFP2, iNAP1, or HyPer, to assess changes in the cytoplasmic ratio of oxidized glutathione to reduced glutathione (GSSG:GSH), and the flux of NADPH and H2O2, respectively. Non-cytotoxic exposure to ISOPOOH resulted in a dose-dependent increase of GSSG:GSH in HAEC that was markedly potentiated by prior glucose deprivation. ISOPOOH-induced increase in glutathione oxidation were accompanied by concomitant decreases in intracellular NADPH. Following ISOPOOH exposure, the introduction of glucose resulted in a rapid restoration of GSH and NADPH, while the glucose analog 2-deoxyglucose resulted in inefficient restoration of baseline GSH and NADPH. To elucidate bioenergetic adaptations involved in combatting ISOPOOH-induced oxidative stress we investigated the regulatory role of glucose-6-phosphate dehydrogenase (G6PD). A knockout of G6PD markedly impaired glucose-mediated recovery of GSSG:GSH but not NADPH. These findings reveal rapid redox adaptations involved in the cellular response to ISOPOOH and provide a live view of the dynamic regulation of redox homeostasis in human airway cells as they are exposed to environmental oxidants.

Thermomechanical Properties and Fracture Toughness Improvement of Thermosetting Vinyl Ester Using Liquid Metal and Graphene Nanoplatelets.

In this study, a eutectic gallium-indium (EGaIn) alloy and graphene nanoplatelets (GnPs) were employed as reinforcements for a comonomer vinyl ester (cVE) resin at different weight fractions up to 2% via a direct polymerization process. First, the effect of EGaIn on the curing kinetics of cVE was evaluated. The thermal and mechanical properties, and the fracture toughness of two types of cVE composites consisting of EGaIn and GnPs were then studied. The results showed that sub-micron sized EGaIn (≤1 wt.%) could promote the curing reaction of cVE without changing the curing mechanism. However, with further increases in EGaIn loading between 1 and 2 wt.%, the curing reaction rate tends to decrease. Both EGaIn and GnPs showed a significant enhancement in strengthening and toughening the cVE matrix with the presence of filler loading up to 1 wt.%. EGaIn was more effective than GnPs in promoting the flexural and impact strength. An increase of up to 50% and 32% were recorded for these mechanical properties, when EGaln was used, as compared to 46%, and 18% for GnPs, respectively. In contrast, the GnPs/cVE composites exhibited a greater improvement in the fracture toughness and fracture energy by up to 50% and 56% in comparison with those of the EGaIn/cVE ones by up to 32% and 39%, respectively. Furthermore, the stiffness of both the EgaIn/cVE and GnPs/cVE composites showed a significant improvement with an increase of up to 1.76 and 1.83 times in the normalized storage modulus, respectively, while the glass transition temperature (Tg) values remained relatively constant. This work highlights the potential of EGaIn being employed as a filler in creating high-performance thermoset composites, which facilitates its widening applications in many structural and engineering fields, where both higher toughness and stiffness are required.

Silk fibroin microfiber-reinforced polycaprolactone composites with enhanced biodegradation and biological characteristics.

There is an enormous demand for bone graft biomaterials to treat developmental and acquired bony defects arising from infections, trauma, tumor, and other conditions. Polycaprolactone (PCL) has been extensively utilized for bone tissue engineering but limited cellular interaction and tissue integration are the primary concerns. PCL-based composites with different biomaterials have been attempted to improve the mechanical and biological response. Interestingly, a few studies have tried to blend PCL with aqueous silk fibroin solution, but the structures prepared with the blend were mechanically weak due to phase mismatch. As a result, silk microparticle-based PCL composites have been prepared, but the microfibers-reinforced composites could be superior to them due to significant fiber-matrix interaction. This study aims at developing a unique composite by incorporating 100-150 µm long (aspect ratio; 8:1-5:1) silk-fibroin microfibers into the PCL matrix for superior biological and mechanical properties. Two silk variants were used, that is, Bombyx mori and a wild variant, Antheraea mylitta, reported to have cell recognizable Arginine-Glycine-Aspartic acid (RGD) sequences. A. mylitta silk fibroin microfibers were produced, and composites were made with PCL for the first time. The morphological, tensile, thermal, biodegradation, and biological properties of the composites were evaluated. Importantly, we tried to optimize the silk concentration within the composite to strike a balance among the cellular response, biodegradation, and mechanical strength of the composites. The results indicate that the PCL-silk fibroin microfiber composite could be an efficient biomaterial for bone tissue engineering.

Mechanistic Impact of Zinc Deficiency in Human Development.

Zinc (Zn) deficiency in humans is an emerging global health issue affecting approximately two billion people across the globe. The situation prevails due to the intake of Zn deficient grains and vegetables worldwide. Clinical identification of Zn deficiency in humans remains problematic because the symptoms do not appear until impair the vital organs, such as the gastrointestinal track, central nervous system, immune system, skeletal, and nervous system. Lower Zn body levels are also responsible for multiple physiological disorders, such as apoptosis, organs destruction, DNA injuries, and oxidative damage to the cellular components through reactive oxygen species (ROS). The oxidative damage causes chronic inflammation lead toward several chronic diseases, such as heart diseases, cancers, alcohol-related malady, muscular contraction, and neuro-pathogenesis. The present review focused on the physiological and growth-related changes in humans under Zn deficient conditions, mechanisms adopted by the human body under Zn deficiency for the proper functioning of the body systems, and the importance of nutritional and nutraceutical approaches to overcome Zn deficiency in humans and concluded that the biofortified food is the best source of Zn as compared to the chemical supplementation to avoid their negative impacts on human.

Three-Dimensional Printing of Customized Scaffolds with Polycaprolactone-Silk Fibroin Composites and Integration of Gingival Tissue-Derived Stem Cells for Personalized Bone Therapy.

Regenerative biomaterials play a crucial role in the success of maxillofacial reconstructive procedures. Yet today, limited options are available when choosing polymeric biomaterials to treat critical size bony defects. Further, there is a requirement for 3D printable regenerative biomaterials to fabricate customized structures confined to the defect site. We present here a 3D printable composite formulation consisting of polycaprolactone (PCL) and silk fibroin microfibers and have established a robust protocol for fabricating customized 3D structures of complex geometry with the composite. The 3D printed composite scaffolds demonstrated higher compressive modulus than 3D printed scaffolds of PCL alone. Furthermore, the compressive modulus of PCL-Antheraea mylitta (AM) silk scaffolds is higher than that of the PCL-Bombyx mori (BM) silk scaffolds at their respective ratios. Compressive modulus of PCL-25AM silk scaffolds (73.4 MPa) is higher than that of PCL-25BM silk scaffolds (65.1 MPa). Compressive modulus of PCL-40AM silk scaffolds (106.1 MPa) is higher than that of PCL-40BM silk scaffolds (77.7 MPa). Moreover, we have isolated, characterized, and integrated human gingival mesenchymal stem cells (hGMSCs), an effective autologous cell source, onto the 3D printed scaffolds to evaluate their bone regeneration potential. The results demonstrated that PCL-silk microfiber composite scaffolds of Antheraea mylitta origin showed much higher bioactivity than the Bombyx mori ones because of arginine-glycine-aspartic acid (RGD) sequences present in the Antheraea mylitta silk fibroin protein favoring cell attachment and proliferation. By day 14, the metabolic activity of hGMSCs was highest in PCL-40AM (4.5 times higher than that at day 1). In addition, to show the translational potential of this work, we have fabricated a patient defect-specific model (mandible) using the CT scan obtained by the micro-CT imaging to understand the printability of the composite for fabricating complex structures to restore maxillofacial bony defects with precision when applied in a clinical scenario.

Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide.

Exposure to respirable air particulate matter (PM2.5) in ambient air is associated with morbidity and premature deaths. A major source of PM2.5 is the photooxidation of volatile plant-produced organic compounds such as isoprene. Photochemical oxidation of isoprene leads to the formation of hydroperoxides, environmental oxidants that lead to inflammatory (IL-8) and adaptive (HMOX1) gene expression in human airway epithelial cells (HAEC). To examine the mechanism through which these oxidants alter intracellular redox balance, we used live-cell imaging to monitor the effects of isoprene hydroxyhydroperoxides (ISOPOOH) in HAEC expressing roGFP2, a sensor of the glutathione redox potential (EGSH). Non-cytotoxic exposure of HAEC to ISOPOOH resulted in a rapid and robust increase in EGSH that was independent of the generation of intracellular or extracellular hydrogen peroxide. Our results point to oxidation of GSH through the redox relay initiated by glutathione peroxidase 4, directly by ISOPOOH or indirectly by ISOPOOH-generated lipid hydroperoxides. We did not find evidence for involvement of peroxiredoxin 6. Supplementation of HAEC with polyunsaturated fatty acids enhanced ISOPOOH-induced glutathione oxidation, providing additional evidence that ISOPOOH initiates lipid peroxidation of cellular membranes. These findings demonstrate that ISOPOOH is a potent environmental airborne hydroperoxide with the potential to contribute to oxidative burden of human airway posed by inhalation of secondary organic aerosols.

Endogenous Streptococcus mitis panophthalmitis in a patient visiting the Dominican Republic.

A 67-year-old woman presented with painful, acute vision loss after 5 days of fever and muscle aches while visiting the Dominican Republic. She had no recent history of ocular surgery, dental work or recent trauma. Anterior chamber aspiration confirmed an initial diagnosis of endogenous endophthalmitis, positive for Streptococcus mitis that progressed to panophthalmitis on return to Canada. Treatment included systemic antibiotics, intravitreal antibiotics and intravitreal dexamethasone. Despite the best medical treatment, the left eye progressed to corneal perforation 5 weeks after presentation. An evisceration with fitted orbital implant was successful in alleviating pain following the surgery. S. mitis is a rare, but possible cause of endogenous endophthalmitis and panophthalmitis. It was important to work with a multidisciplinary and global team to coordinate and offer appropriate treatment measures. Although vision was lost, evisceration of the left eye provided ocular comfort and good cosmetic outcomes for the patient.