Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation.

Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.

Reproducibility of methods required to identify and characterize nanoforms of substances.

Nanoforms (NFs) of a substance may be distinguished from one another through differences in their physicochemical properties. When registering nanoforms of a substance for assessment under the EU REACH framework, five basic descriptors are required for their identification: composition, surface chemistry, size, specific surface area and shape. To make the risk assessment of similar NFs efficient, a number of grouping frameworks have been proposed, which often require assessment of similarity on individual physicochemical properties as part of the group justification. Similarity assessment requires an understanding of the achievable accuracy of the available methods. It must be demonstrated that measured differences between NFs are greater than the achievable accuracy of the method, to have confidence that the measured differences are indeed real. To estimate the achievable accuracy of a method, we assess the reproducibility of six analytical techniques routinely used to measure these five basic descriptors of nanoforms: inductively coupled plasma mass spectrometry (ICP-MS), Thermogravimetric analysis (TGA), Electrophoretic light scattering (ELS), Brunauer-Emmett-Teller (BET) specific surface area and transmission and scanning electron microscopy (TEM and SEM). Assessment was performed on representative test materials to evaluate the reproducibility of methods on single NFs of substances. The achievable accuracy was defined as the relative standard deviation of reproducibility (RSDR) for each method. Well established methods such as ICP-MS quantification of metal impurities, BET measurements of specific surface area, TEM and SEM for size and shape and ELS for surface potential and isoelectric point, all performed well, with low RSDR, generally between 5 and 20%, with maximal fold differences usually <1.5 fold between laboratories. Applications of technologies such as TGA for measuring water content and putative organic impurities, additives or surface treatments (through loss on ignition), which have a lower technology readiness level, demonstrated poorer reproducibility, but still within 5-fold differences. The expected achievable accuracy of ICP-MS may be estimated for untested analytes using established relationships between concentration and reproducibility, but this is not yet the case for TGA measurements of loss on ignition or water content. The results here demonstrate an approach to estimate the achievable accuracy of a method that should be employed when interpreting differences between NFs on individual physicochemical properties.

Socioeconomic Status and Risk of Bleeding After Mechanical Aortic Valve Replacement.

BACKGROUND: Whether low socioeconomic status (SES) is associated with increased risk of anticoagulation-related adverse events in patients with mechanical heart valves is unknown. OBJECTIVES: This study sought to investigate the impact of patients' SES on the risk of bleeding after mechanical aortic valve replacement (AVR). METHODS: This nationwide population-based cohort study included all patients aged 18-70 years who underwent mechanical AVR in Sweden from 1997 to 2018. Data were obtained from the SWEDEHEART register and other national health data registers. The exposure was quartiles of household disposable income. The primary outcome was hospitalization for a bleeding event. RESULTS: Among 5974 patients, the absolute risk for bleeding after 20 years of follow-up was 20% (95% CI: 17%-24%) in the lowest income quartile (Q1) and 16% (95% CI: 13%-20%) in the highest quartile (Q4). The risk of bleeding decreased with increasing income level and was significantly lower in patients in income level Q3 (HR: 0.77; 95% CI: 0.60-0.99) and Q4 (HR: 0.68; 95% CI: 0.50-0.92) than Q1. The risk of death from intracranial hemorrhage was five times higher in the lowest income quartile than the age- and sex-matched general Swedish population (standardized mortality ratio: 5.0; 95% CI: 3.3-7.4). CONCLUSIONS: We observed a strong association between SES and risk of bleeding among patients who underwent mechanical AVR. These findings suggest suboptimal anticoagulation treatment in patients with lower SES and the need for strategies to optimize anticoagulation treatment in patients with a mechanical heart valve. (Health-Data Register Studies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950).

Food contact of paper and plastic products containing SiO2, Cu-Phthalocyanine, Fe2O3, CaCO3: Ranking factors that control the similarity of form and rate of release.

The paper industry is an important sector annually consuming kilotons of nanoforms and non-nanoforms of fillers and pigments. Fillers accelerate the rate of drying (less energy needed) and product cost (increasing the load of low-cost fillers). The plastic industry is another use sector, where coloristic pigments can be in nanoform, and many food containers are made of plastic. Use of paper to wrap both wet and dry food is consumer practice, but not always intended by producers. Here we compare the release behavior of different nano-enabled products (NEPs) by changing a) nanoform (NF) characteristics, b) NF load, c) the nano-enabled product (NEP) matrix, and d) food simulants. The ranking of these factors enables an assessment of food contact by concepts of analogy, specifically via the similarities of the rate and form of release in food during contact. Three types of matrices were used: Paper, plastic ((Polylactic Acid (PLA), Polyamide (PA6), and Polyurethane (PU)), and a paint formulation. Two nanoforms each of SiO2, Fe2O3, Cu-Phthalocyanine were incorporated, additionally to the conventional form of CaCO3 that is always contained in paper to reduce cellulose consumption. Tests were guided by the European Regulation EC 1935/2004 and EU 10/2011. No evidence of particle release was observed: the qualitative similarity (the form of release) was high regarding the food contact of all NEPs with embedded NFs. Quantitative similarity of releases depended primarily on the NEP matrix, as this controls the penetration of the simulant fluid into the NEP. The solubility of the NF and impurities in the simulant fluid was the second decisive factor, as dissolution of the NF inside the NEP is the main mechanism of release. This led to complete removal of CaCO3 in acidic medium, whereas Fe and Si signals remained in the paper, consistent with the low release rates in an ionic form. In our set of 16 NEPs, only one NEP showed a dependence on the REACH NF descriptors (substance, size, shape, surface treatment, crystallinity, impurities), specifically attributed to differences in soluble impurities, whereas for all others the substance of the nanoform was sufficient to predict a similarity of food contact release, without influences of size, shape, surface treatment and crystallinity.

Comparison of Long-term Performance of Bioprosthetic Aortic Valves in Sweden From 2003 to 2018.

IMPORTANCE: The performance of bioprosthetic aortic valves is usually assessed in single valve models or head-to-head comparisons. National databases or registries offer the opportunity to investigate all available valve models in the population and allows for a comparative assessment of their performance. OBJECTIVE: To analyze the long-term rates of reintervention, all-cause mortality, and heart failure hospitalization associated with commonly used bioprosthetic aortic valves and to identify valve model groups with deviation in clinical performance. DESIGN, SETTING, AND PARTICIPANTS: This population-based, nationwide cohort study included all adult patients who underwent surgical aortic valve replacement (with or without concomitant coronary artery bypass surgery or ascending aortic surgery) in Sweden between January 1, 2003, and December 31, 2018. Patients were identified from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. Patients with concomitant valve surgery, previous cardiac surgery, and previous transcatheter valve replacement were excluded. Follow-up was complete for all participants. Data were analyzed from March 9, 2020, to October 12, 2021. EXPOSURES: Primary surgical aortic valve replacement with the Perimount, Mosaic/Hancock, Biocor/Epic, Mitroflow/Crown, Soprano, and Trifecta valve models. MAIN OUTCOMES AND MEASURES: The primary outcome was cumulative incidence of reintervention, defined as a subsequent aortic valve operation or transcatheter valve replacement. Secondary outcomes were all-cause mortality and heart failure hospitalization. Regression standardization and flexible parametric survival models were used to account for intergroup differences. Mean follow-up time was 7.1 years, and maximum follow-up time was 16.0 years. RESULTS: A total of 16 983 patients (mean [SD] age, 72.6 [8.5] years; 10 685 men [62.9%]) were included in the analysis. The Perimount valve model group had the lowest and the Mitroflow/Crown valve model group had the highest cumulative incidence of reintervention. The estimated cumulative incidence of reintervention at 10 years was 3.6% (95% CI, 3.1%-4.2%) in the Perimount valve model group and 12.2% (95% CI, 9.8%-15.1%) in the Mitroflow/Crown valve model group. The estimated incidence of reintervention at 10 years was 9.3% (95% CI, 7.3%-11.3%) in the Soprano valve model group. CONCLUSIONS AND RELEVANCE: Results of this study showed that the Perimount valve was the most commonly used and had the lowest incidence of reintervention, all-cause mortality, and heart failure hospitalization, whereas the Mitroflow/Crown valve had the highest rates. These findings highlight the need for clinical vigilance in patients who receive either a Soprano or Mitroflow/Crown aortic bioprosthesis.

pH-Controlled assembly of polyelectrolyte layers on silica nanoparticles in concentrated suspension.

HYPOTHESIS: Preparation of suspensions of nanoparticles (>1 wt%) coated with a polyelectrolyte multilayers is a challenging task because of the risk of flocculation when a polyelectrolyte is added to a suspension of oppositely charged nanoparticles. This situation can be avoided if the charge density of the polymers and particles is controlled during mixing so as to separate mixing and adsorption events. EXPERIMENTS: The cationic polyethylenimine (PEI) and the anionic carboxymethylcellulose (CMC) were used as weak polyelectrolytes. Polyelectrolyte multilayers build-up was conducted by reducing the charge of one of the components during the addition of the next component. Charge density was controlled by tuning pH. Analysis of the suspension of coated nanoparticles was done by means of dynamic light scattering, electrophoresis and small angle x-ray scattering measurements, while quartz crystal microbalance was used to study the build-up process on flat silica surfaces. FINDINGS: Charge density, controlled through pH, can be used as a tool to avoid flocculation during layer-by-layer deposition of polyelectrolytes on 20 nm silica particles at high concentration (∼40 wt%). When added to silica at pH 3, PEI did not induce flocculation. Adsorption was triggered by raising the pH to 11, pH at which CMC could be added. The pH was then lowered to 3. The process was repeated, and up to five polyelectrolyte layers were deposited on concentrated silica nanoparticles while inducing minimal aggregation.

Sex and Permanent Pacemaker Implantation After Surgical Aortic Valve Replacement.

BACKGROUND: We performed a nationwide population-based cohort study to investigate sex differences in the rate of permanent pacemaker implantation after surgical aortic valve replacement (AVR). METHODS: This study included all adult patients who underwent primary AVR in Sweden between 2005 and 2018. Study data were obtained from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry and other Swedish national health-data registers. The rate of permanent pacemaker implantation within 30 days of surgery AVR was compared between men and women. We estimated propensity scores that were used for inverse probability of treatment weighting to account for sex differences in patient characteristics. RESULTS: A total of 18 131 patients were included, 11 657 men (64%) and 6474 women (36%). The rate of permanent pacemaker implantation did not differ between women (3.8%; 95% CI, 3.2%-4.3%) and men (3.7%; 95% CI, 3.3%-4.1%; P = .831). In patients aged <60 years, the rate of permanent pacemaker implantation was significantly higher in women (6.2%; 95% CI, 4.3%-8.0%) than in men (3.6%; 95% CI, 2.8%-4.4%; P = .006). The odds of pacemaker implantation in patients aged <60 years was significantly higher in women (odds ratio, 1.76; 95% CI, 1.17-2.63; P = .006). In patients aged 60 to 79 years and ≥80 years, the rate of pacemaker implantation did not differ between men and women. CONCLUSIONS: The rate of permanent pacemaker implantation after surgical AVR in patients aged <60 years was higher in women than in men. The susceptibility to conduction disturbances requiring permanent pacemaker implantation in women aged <60 years warrants further investigation and should be recognized as transcatheter aortic valve replacement expands into younger patients.

Permanent pacemaker implantation after On-X surgical aortic valve replacement: SWEDEHEART observational study.

OBJECTIVE: Bioprosthetic aortic valves with an extended subannular component, such as transcatheter valves, exert increased compression on the cardiac conduction system and increase the risk for permanent pacemaker implantation. It is unknown if the On-X mechanical prosthetic valve, which has an elongated subannular valve housing, increases the risk of permanent pacemaker implantation following aortic valve replacement. DESIGN: Observational nationwide cohort study. SETTING: Swedish population-based study. PARTICIPANTS: All patients aged 18-65 years who underwent primary mechanical aortic valve replacement in Sweden between 2005 and 2018. We used the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register and other Swedish national health-data registers. EXPOSURE: Patients implanted with an On-X valve versus patients implanted with other bileaflet mechanical valves. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was permanent pacemaker implantation within 30 days of surgery. RESULTS: A total of 2602 patients were included, and 581 patients received an On-X valve and 2021 patients received a St Jude Masters/Regent (n=945) or Carbomedics Reduced valve (n=1076). In the total study population, 115 (4.4%) permanent pacemaker implantations were performed within 30 days after aortic valve replacement. In the propensity score matched population, there was no significant difference in the rate of permanent pacemaker implantation in the On-X group compared with the control group: 3.6% (95% CI: 2.4% to 5.5%) vs 4.0% (95% CI: 2.7% to 5.9%), p=0.877. CONCLUSIONS: The On-X prosthetic heart valve was associated with a similarly low risk for permanent pacemaker implantation after aortic valve replacement compared with other conventional bileaflet mechanical valves. The On-X elongated subannular valve housing does not interfere with the cardiac conduction system.

Cause of Death After Surgical Aortic Valve Replacement: SWEDEHEART Observational Study.

Background Prior studies showed that life expectancy in patients who underwent surgical aortic valve replacement (AVR) was lower than in the general population. Explanations for this shorter life expectancy are unknown. The aim of this nationwide, observational cohort study was to investigate the cause-specific death following surgical AVR. Methods and Results We included 33 018 patients who underwent primary surgical AVR in Sweden between 1997 and 2018, with or without coronary artery bypass grafting. The SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register and other national health-data registers were used to obtain and characterize the study cohort and to identify causes of death, categorized as cardiovascular mortality, cancer mortality, or other causes of death. The relative risks for cause-specific mortality in patients who underwent AVR compared with the general population are presented as standardized mortality ratios. During a mean follow-up period of 7.3 years (maximum 22.0 years), 14 237 (43%) patients died. The cumulative incidence of death from cardiovascular, cancer-related, or other causes was 23.5%, 8.3%, and 11.6%, respectively, at 10 years, and 42.8%, 12.8%, and 23.8%, respectively, at 20 years. Standardized mortality ratios for cardiovascular, cancer-related, and other causes of death were 1.79 (95% CI, 1.75-1.83), 1.00 (95% CI, 0.97-1.04), and 1.08 (95% CI, 1.05-1.12), respectively. Conclusions We found that life expectancy following AVR was lower than in the general population. Lower survival after AVR was explained by an increased relative risk of cardiovascular death. Future studies should focus on the role of earlier surgery in patients with asymptomatic aortic stenosis and on optimizing treatment and follow-up after AVR. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02276950.

Long-term Outcomes Associated With Permanent Pacemaker Implantation After Surgical Aortic Valve Replacement.

Importance: Prior studies investigating the long-term clinical outcomes of patients who have undergone permanent pacemaker implantation after aortic valve replacement reported conflicting results. Objective: To investigate long-term outcomes after primary surgical aortic valve replacement among patients who underwent postoperative permanent pacemaker implantation. Design, Setting, and Participants: This cohort study included all patients who underwent surgical aortic valve replacement in Sweden from 1997 to 2018. All patients who underwent primary surgical aortic valve replacement in Sweden and survived the first 30 days after surgical treatment were included. Patients who underwent preoperative permanent pacemaker implantation, concomitant surgical treatment for another valve, or emergency surgical treatment were excluded. Patients who underwent concomitant coronary artery bypass grafting or surgical treatment of the ascending aorta were included. Follow-up data were complete for all patients. Data were analyzed from October through December 2020. Exposures: Patients underwent implantation of a permanent pacemaker or implantable cardioverter defibrillator within 30 days after aortic valve replacement. Main Outcomes and Measures: The primary outcome was all-cause mortality. Results: Among 24 983 patients who underwent surgical aortic valve replacement, 849 patients (3.4%) underwent permanent pacemaker implantation within 30 days after surgical treatment and 24 134 patients (96.6%) did not receive pacemakers in that time. The mean (SD) age of the total study population was 69.7 (10.8) years, and 9209 patients were women (36.9%). The mean (SD) and maximum follow-up periods were 7.3 (5.0) years and 22.0 years, respectively. At 10 years and 20 years after surgical treatment, the Kaplan-Meier estimated survival rates were 52.8% and 18.0% in the pacemaker group, respectively, and 57.5% and 19.6% in the nonpacemaker group, respectively. All-cause mortality was statistically significantly increased in the pacemaker group compared with the nonpacemaker group (hazard ratio [HR], 1.14; 95% CI, 1.01-1.29; P = .03), and so was risk of heart failure hospitalization (HR, 1.58; 95% CI, 1.31-1.89; P < .001). No statistically significant increase was found in the risk of endocarditis in the pacemaker group. Conclusions and Relevance: This study found that there were increased risks of all-cause mortality and heart failure hospitalization among patients who underwent permanent pacemaker implantation after surgical aortic valve replacement, suggesting that these risks are important considerations, especially in an era when transcatheter aortic valve replacement is used in younger patients at lower risk of adverse surgical outcomes. These findings further suggest that future research should investigate how to avoid permanent pacemaker dependency after surgical and transcatheter aortic valve replacement.

Variation in dissolution behavior among different nanoforms and its implication for grouping approaches in inhalation toxicity.

Different nanoforms (NF) of the same substance each need to be registered under REACH, but similarities in physiological interaction -among them biodissolution- can justify read-across within a group of NFs, thereby reducing the need to perform animal studies. Here we focused on the endpoint of inhalation toxicity and explored how differences in physical parameters of 17 NFs of silica, and organic and inorganic pigments impact dissolution rates, half-times, and transformation under both pH 7.4 lung lining conditions and pH 4.5 lysosomal conditions. We benchmarked our observations against well-known TiO2, BaSO4 and ZnO nanomaterials, representing very slow, partial and quick dissolution respectively. By automated image evaluation, structural transformations were observed for dissolution rates in the order of 0.1 to 10 ng/cm2/h, but did not provide additional decision criteria on the similarity of NFs. Dissolution half-times spanned nearly five orders of magnitude, mostly dictated by the substance and simulant fluid, but modulated up to ten-fold by the subtle differences between NFs. Physiological time scales and benchmark materials help to frame the biologically relevant range, proposed as 1 h to 1 y. NFs of ZnO, Ag, SiO2, BaSO4 were in this range. We proposed numerical rules of pairwise similarity within a group, of which the worst case NF would be further assessed by in vivo inhalation studies. These rules divided the colloidal silica NFs into two separate candidate groups, one with Al-doping, one without. Shape or silane surface treatment were less important. The dissolution halftimes of many organic and inorganic pigment NFs were longer than the biologically relevant range, such that dissolution behavior is not an obstacle for their groupings.

Importance of the number emission factor of combustion-generated aerosols from nano-enabled products.

Accidental or open waste burning and incineration of nano-enabled products (NEPs) might lead to the release of incidental aerosols in the nano size range into the environment resulting in harmful effects on humans. We have investigated combustion-generated aerosol release during accidental burning for several real-life NEPs such as paints with silica (SiO2) and spruce wood panels containing SiO2 and Fe2O3 nanomaterials (NMs), paper with SiO2 and Fe2O3 NMs and polymeric composites with CuPhthtalocyanine NMs in poly lactic acid (PLA), polyamide 6 (PA6) and thermoplastic pol-urethane (TPU) matrices. Chemical compositions, aerosols number emission factors (nefs) and concentrations of the signature elements of the NMs of the combustion-generated aerosols were investigated. In addition, the residual ash was analyzed. The outcomes of this study shed light on how NM and matrix types influenced the properties of the released aerosols. Based on our results it was established that the combustion-generated aerosols were composed of transformed NMs with modified physical-chemical characteristics compared to the pristine NMs. In addition to aerosols with transformed NMs, there were also particles due to incomplete combustion of the matrix. Types of the pristine NMs and matrices affected the characteristics of the released aerosols. Since the effect of the aerosols is related to the inhaled aerosol number concentration, the nef is an important parameter. Our results showed that the nefs in the size range of 5.6 to 560 nm depended strongly on the type of combusted NEP, which indicated that the NEPs could be categorized according to their potential to release aerosols in this size range when they were burnt. The generated release data facilitate the assessment of human and environmental exposure and the associated risk assessment of combustion-generated aerosols from NEPs.

Porcine vs Bovine Bioprosthetic Aortic Valves: Long-Term Clinical Results.

BACKGROUND: Previous studies have reported superior hemodynamic performance with bovine bioprosthetic aortic valves compared with porcine valves. However, conflicting results mean the long-term effect on survival is not well known. The aim of this study was to examine long-term survival, rate of aortic valve reoperations, and heart failure hospitalizations after surgical aortic valve replacement (AVR) with porcine vs bovine bioprosthetic valves. METHODS: This was a population-based cohort study including all patients who had undergone AVR in Sweden from 1995 to 2012, with or without concomitant coronary artery bypass grafting. Patients were identified through the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry. Baseline and outcome data were gathered from national registries. Propensity scores and inverse probability of treatment weighting were used to control for intergroup differences. Analyses accounted for competing risk of death when appropriate. RESULTS: A total of 12,845 patients underwent AVR with porcine (n = 4198) or bovine (n = 8647) prostheses. We found a small but significant difference in mortality favoring porcine prostheses: 78% vs 76%, 47% vs 43%, and 17% vs 15% at 5, 10, and 15 years, respectively (hazard ratio, 0.90; 95% confidence interval, 0.85-0.96). Porcine prostheses were associated with an increased risk of reoperation (hazard ratio, 1.48; 95% confidence interval, 1.11-1.98), but no difference in the risk of heart failure hospitalization. Results were similar in patients who underwent isolated AVR. CONCLUSIONS: Consistent with previous reports, we found that patients receiving porcine prostheses had a higher rate of reoperation compared with bovine prostheses. However, porcine prostheses were associated with improved long-term survival compared with bovine prostheses.

A strategy for synergistic ethanol yield and improved production predictability through blending feedstocks.

BACKGROUND: The integration of first- and second-generation bioethanol processes has the potential to accelerate the establishment of second-generation bioethanol on the market. Cofermenting pretreated wheat straw with a glucose-rich process stream, such as wheat grain hydrolysate, in a simultaneous saccharification and fermentation process could address the technical issues faced during the biological conversion of lignocellulose to ethanol. For example, doing so can increase the final ethanol concentration in the broth and mitigate the effects of inhibitors formed during the pretreatment. Previous research has indicated that blends of first- and second-generation substrates during simultaneous saccharification and fermentation have synergistic effects on the final ethanol yield, an important parameter in the process economy. In this study, enzymatic hydrolysis and simultaneous saccharification and fermentation were examined using blends of pretreated wheat straw and saccharified wheat grain at various ratios. The aim of this study was to determine the underlying mechanisms of the synergy of blending with regard to the yield and volumetric productivity of ethanol. RESULTS: Replacing 25% of the pretreated wheat straw with wheat grain hydrolysate during simultaneous saccharification and fermentation was sufficient to decrease the residence time needed to deplete soluble glucose from 96 to 24 h and shift the rate-limiting step from ethanol production to the rate of enzymatic hydrolysis. Further, a synergistic effect on ethanol yield was observed with blended substrates, coinciding with lower glycerol production. Also, blending substrates had no effect on the yield of enzymatic hydrolysis. CONCLUSIONS: The effects of substrate blending on the volumetric productivity of ethanol were attributed to changes in the relative rates of cell growth and cell death due to alterations in the concentrations of substrate and pretreatment-derived inhibitors. The synergistic effect of substrate blending on ethanol yield was attributed in part to the decreased production of cell mass and glycerol. Thus, it is preferable to perform simultaneous saccharification and fermentation with substrate blends rather than pure substrates with regard to yield, productivity, and the robustness of the process.

Nanomaterials for Combined Stabilisation and Deacidification of Cellulosic Materials-The Case of Iron-Tannate Dyed Cotton.

The conservation of textiles is a challenge due to the often fast degradation that results from the acidity combined with a complex structure that requires remediation actions to be conducted at several length scales. Nanomaterials have lately been used for various purposes in the conservation of cultural heritage. The advantage with these materials is their high efficiency combined with a great control. Here, we provide an overview of the latest developments in terms of nanomaterials-based alternatives, namely inorganic nanoparticles and nanocellulose, to conventional methods for the strengthening and deacidification of cellulose-based materials. Then, using the case of iron-tannate dyed cotton, we show that conservation can only be addressed if the mechanical strengthening is preceded by a deacidification step. We used CaCO3 nanoparticles to neutralize the acidity, while the stabilisation was addressed by a combination of nanocellulose, and silica nanoparticles, to truly tackle the complexity of the hierarchical nature of cotton textiles. Silica nanoparticles enabled strengthening at the fibre scale by covering the fibre surface, while the nanocellulose acted at bigger length scales. The evaluation of the applied treatments, before and after an accelerated ageing, was assessed by tensile testing, the fibre structure by SEM and the apparent colour changes by colourimetric measurements.

Loss in Life Expectancy After Surgical Aortic Valve Replacement: SWEDEHEART Study.

BACKGROUND: Contemporary data on loss in life expectancy after aortic valve replacement (AVR) are scarce, particularly in younger patients. OBJECTIVES: The purpose of this national, observational cohort study was to analyze long-term relative survival and estimated loss in life expectancy after AVR. METHODS: The study included 23,528 patients who underwent primary surgical AVR with or without concomitant coronary artery bypass grafting in Sweden between 1995 and 2013 from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register. Individual level linking with other national health-data registers was performed to obtain baseline characteristics and vital status. The expected survival from the general Swedish population matched by age, sex, and year of surgery was obtained from the Human Mortality Database. The relative survival was used as an estimate of cause-specific mortality. Flexible parametric models based on relative survival were used to estimate the loss in life expectancy. RESULTS: The mean follow-up was 6.8 years. The 19-year observed, expected, and relative survival was 21%, 34%, and 63% (95% confidence interval [CI]: 59% to 67%), respectively. The loss in life expectancy was 1.9 years (95% CI: 1.2 to 2.6 years) in the total study population. The estimated loss in life expectancy increased with younger age: 0.4 years (95% CI: 0.3 to 0.5 years) versus 4.4 years (95% CI: 1.5 to 7.2 years) in patients ≥80 and <50 years of age, respectively. There was no difference in loss in life expectancy between men and women. CONCLUSIONS: This study found a shorter life expectancy in patients after AVR compared with the general population. The estimated loss in life expectancy was substantial, and increased with younger age. These results provide important information to quantify disease burden after AVR, and are relevant for clinicians counseling patients before and after AVR. (HeAlth-data Register sTudies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950).

ABO blood type and risk of porcine bioprosthetic aortic valve degeneration: SWEDEHEART observational cohort study.

OBJECTIVE: Blood type A antigen on porcine aortic bioprostheses might initiate an immune reaction leading to an increased frequency of structural valve deterioration in patients with blood type B or O. The aim was to analyse the association between ABO blood type and porcine bioprosthetic aortic valve degeneration. DESIGN: Observational nationwide cohort study. SETTING: Swedish population-based study. PARTICIPANTS: Adult patients (n=3417) who underwent surgical aortic valve replacement and received porcine bioprosthetic aortic valves between 1995 and 2012 from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register. The study database was enriched with information from other national registers. EXPOSURE: The patients were categorised into type A/AB and type B/O blood groups. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was aortic valve reoperation, and secondary outcomes were heart failure and all-cause mortality. We report risk estimates that account for the competing risk of death. RESULTS: In total, 3417 patients were identified: 1724 (50.5%) with blood type A/AB and 1693 (49.5%) with blood type B/O. Both groups had similar baseline characteristics. The cumulative incidence of aortic valve reoperation was 3.4% (95% CI 2.5% to 4.4%) and 3.6% (95% CI 2.6% to 4.6%) in the type B/O and the A/AB group, respectively, at 15 years of follow-up (absolute risk difference: -0.2% (95% CI -1.5% to 1.2%)). There was no significantly increased risk for aortic valve reoperation in patients with blood type B/O compared with type A/AB (HR 0.95, 95% CI 0.62 to 1.45). There was no significant difference in absolute or relative risk of heart failure or death between the groups. CONCLUSIONS: We found no significant association between patient blood type and clinical manifestations of structural valve deterioration following porcine aortic valve replacement. Our findings suggest that it is safe to use porcine bioprosthetic valves without consideration of ABO blood type in the recipient. TRIAL REGISTRATION NUMBER: NCT02276950.

Surgery for pulmonary metastases from colorectal cancer: survival and prognostic factors.

BACKGROUND: This study aimed to describe overall survival following pulmonary metastasectomy for colorectal cancer (CRC) in Sweden, and to assess the discrimination of a recently proposed risk prediction model. METHODS: Individual-level data of 756 patients who underwent resection of pulmonary metastases from CRC between 2009 and 2015 were obtained from ThoR, a Swedish national quality register for thoracic surgery. We classified patients into three risk categories according to the number of preoperative risk factors [age, disease-free interval (DFI), presence of extrathoracic lesions, number of pulmonary metastases] established in a prior study. We estimated the hazard ratios (HRs) and 95% confidence interval (CI) by Cox regression and the restricted mean survival time difference as group contrast measures. RESULTS: During a median follow-up time of 2.9 years, 35% (268/756) patients died. At 5 years, overall survival was 56% (95% CI: 51-60%). In a Cox regression model with risk category as the only independent variable, the HR for all-cause mortality was 1.94 (95% CI: 1.38-2.72, P<0.001) and 4.35 (95% CI: 2.49-7.62, P<0.001) in the moderate- (n=558) and high-risk categories (n=32), respectively, versus the low-risk category (n=166). At 5 years, the differences in restricted mean survival time were 6 months (P<0.001) and 1.5 years (P<0.001) in the moderate- and high-risk categories, respectively, versus the low-risk category. CONCLUSIONS: Five-year survival after surgery for pulmonary metastases from CRC in Sweden was similar or higher compared with contemporary reports. A prognostic model, initially developed in Japanese patients, had excellent discrimination in an external validation cohort of Swedish patients.