Comparison of Physicochemical Characteristics and Biostimulatory Functions in Two Calcium Hydroxyapatite-Based Dermal Fillers.

BACKGROUND:   Dermal fillers containing calcium hydroxyapatite (CaHA) are categorized as biostimulatory. However, differences in CaHA biomaterial likely affect the resultant induction of collagen synthesis, and variability in microsphere shape and size likely influences a patient’s immune response. This study compares 2 CaHA based fillers: one suspended in carboxymethylcellulose (denoted "CaHA/CMC"), and one crosslinked with 1,4-butanediol diglycidyl ether to hyaluronic acid (denoted "CaHA/HA"). OBJECTIVE: To characterize CaHA/CMC and CaHA/HA fillers to stimulate in vitro collagen biosynthesis. METHODS: Physicochemical evaluations included G′ and extrusion force. Scanning electron microscopy (SEM) was used to characterize isolated CaHA microspheres and freeze-dried formulations. Collagen I and III expression were evaluated using immunofluorescence. RESULTS: CaHA/CMC showed higher G′ (P<0.001) and lower extrusion force (P=0.0003), with uniform polymeric-matrix interactions, compared with CaHA/HA. On SEM, isolated microspheres and freeze-dried CaHA/CMC showed round and smooth surfaced microspheres of similar size. Isolated microspheres and freeze-dried CaHA/HA showed nonhomogeneous, broken microspheres, of various sizes, with fragments embedded in the polymer matrix. Although both fillers induced collagen III expression, only CaHA/CMC induced longer-lasting collagen I expression, with increases of 123% (P=0.007) and 164% (P<0.0001) at 2 and 5 mg/mL, respectively, compared with control. CaHA/CMC also increased collagen I expression at equivalent CaHA microsphere concentrations at 2 (P=0.0052) and 5 mg/mL (P<0.0001), compared with CaHA/HA. CONCLUSION: The physicochemical characteristics selected for evaluation were more favorable for CaHA/CMC than CaHA/HA. When compared with CaHA/HA, the smooth, homogeneous microsphere composition of CaHA/CMC promoted significantly more collagen I biosynthesis, an essential process for tissue augmentation and long-lasting aesthetic improvement. Citation: Kunzler C, Hartmann C, Nowag B, et al. Comparison of physicochemical characteristics and biostimulatory functions in two calcium hydroxyapatite-based dermal fillers. J Drugs Dermatol. 2023;22(9):910-916. doi:10.36849/JDD.7684.

Deconstruction of biomass enabled by local demixing of cosolvents at cellulose and lignin surfaces.

A particularly promising approach to deconstructing and fractionating lignocellulosic biomass to produce green renewable fuels and high-value chemicals pretreats the biomass with organic solvents in aqueous solution. Here, neutron scattering and molecular-dynamics simulations reveal the temperature-dependent morphological changes in poplar wood biomass during tetrahydrofuran (THF):water pretreatment and provide a mechanism by which the solvent components drive efficient biomass breakdown. Whereas lignin dissociates over a wide temperature range (>25 °C) cellulose disruption occurs only above 150 °C. Neutron scattering with contrast variation provides direct evidence for the formation of THF-rich nanoclusters (Rg ∼ 0.5 nm) on the nonpolar cellulose surfaces and on hydrophobic lignin, and equivalent water-rich nanoclusters on polar cellulose surfaces. The disassembly of the amphiphilic biomass is thus enabled through the local demixing of highly functional cosolvents, THF and water, which preferentially solvate specific biomass surfaces so as to match the local solute polarity. A multiscale description of the efficiency of THF:water pretreatment is provided: matching polarity at the atomic scale prevents lignin aggregation and disrupts cellulose, leading to improvements in deconstruction at the macroscopic scale.

Impact of change in bedtime variability on body composition and inflammation: secondary findings from the Go Red for Women Strategically Focused Research Network.

Variability in daily sleep patterns is an emerging factor linked to metabolic syndrome. However, whether reducing bedtime variability improves markers of disease risk has not been tested. Here, we assessed whether body composition and inflammation were impacted by changes in bedtime variability over a 6-week period, during which, women were instructed to maintain healthy, habitual sleep (HS) patterns (one arm of a randomized trial). Data were available for 37 women (age 34.9 ± 12.4 years, BMI 24.7 ± 2.9 kg/m2, sleep duration 7.58 ± 0.49 h/night). Body composition and leukocyte platelet aggregates (LPA) were measured at baseline and endpoint using magnetic resonance imaging and flow cytometry, respectively. Sleep data were collected daily using wrist actigraphy. Change in bedtime variability was calculated as the difference in the standard deviation (SD) of bedtimes measured during the 2-week screening period and the 6-week intervention period. Results showed that women who reduced their bedtime variability (n = 29) during the intervention had reductions in total (P < 0.001) and subcutaneous adipose tissue (P < 0.001) relative to women who increased/maintained (n = 8) bedtime variability. Similar effects were observed for LPA levels between women who reduced vs increased/maintained bedtime variability (P = 0.011). Thus, reducing bedtime variability, without changing sleep duration, could improve cardiometabolic health by reducing adiposity and inflammation.

Hemicellulose-Cellulose Composites Reveal Differences in Cellulose Organization after Dilute Acid Pretreatment.

Model hemicellulose-cellulose composites that mimic plant cell wall polymer interactions were prepared by synthesizing deuterated bacterial cellulose in the presence of glucomannan or xyloglucan. Dilute acid pretreatment (DAP) of these materials was studied using small-angle neutron scattering, X-ray diffraction, and sum frequency generation spectroscopy. The macrofibril dimensions of the pretreated cellulose alone were smaller but with similar entanglement of macrofibrillar network as native cellulose. In addition, the crystallite size dimension along the (010) plane increased. Glucomannan-cellulose underwent similar changes to cellulose, except that the macrofibrillar network was more entangled after DAP. Conversely, in xyloglucan-cellulose the macrofibril dimensions and macrofibrillar network were relatively unchanged after pretreatment, but the cellulose Iß content was increased. Our results point to a tight interaction of xyloglucan with microfibrils while glucomannan only interacts with macrofibril surfaces. This study provides insight into roles of different hemicellulose-cellulose interactions and may help in improving pretreatment processes or engineering plants with decreased recalcitrance.

Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: THERMODYNAMIC STABILITY CORRELATES WITH RATES OF UNFOLDING RATHER THAN FOLDING.

Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. FNIII domains are one of the most common protein folds and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical seven-strand ß-sandwich structure, but they vary widely in sequence and thermodynamic stability. We assayed thermodynamic stability of each domain by equilibrium denaturation in urea. We then assayed the kinetics of domain opening and closing by a technique known as thiol exchange. For this we introduced a buried Cys at the identical location in each FNIII domain and measured the kinetics of labeling with DTNB over a range of urea concentrations. A global fit of the kinetics data gave the kinetics of spontaneous unfolding and refolding in zero urea. We found that the folding rates were relatively similar, ∼0.1-1 s-1, for the different domains. The unfolding rates varied widely and correlated with thermodynamic stability. Our study is the first to address this question using a set of domains that are structurally homologous but evolved with widely varying sequence identity and thermodynamic stability. These data add new evidence that thermodynamic stability correlates primarily with unfolding rate rather than folding rate. The study also has implications for the question of whether opening of FNIII domains contributes to the stretching of fibronectin matrix fibrils.

Pseudophakic mini-monovision: high patient satisfaction, reduced spectacle dependence, and low cost.

BACKGROUND: Cataract surgery with pseudophakic mini-monovision has lower out-of-pocket patient expense than premium multifocal intraocular lenses (IOL). The purpose of this study was to evaluate patient-reported satisfaction and spectacle dependence for key activities of daily living after cataract surgery with pseudophakic mini-monovision. The study also examined statistical relationships between patient demographic variables, visual acuity and satisfaction. METHODS: Prospective cohort study of 56 patients (112 eyes) who underwent bilateral cataract surgery with pseudophakic mini-monovision. Mini-monovision corrects one eye for distance vision and the other eye is focused at near with - 0.75 to - 1.75 D of myopia. All patients with 1 diopter or greater of corneal astigmatism had a monofocal toric IOLs implanted or limbal relaxing incision. The main study outcomes were assessed at the last follow-up appointment and included refraction, visual acuity, patient reported spectacle use, and patient satisfaction. Descriptive statistics, correlation matrixes and Pearson's chi-square tests were examined. RESULTS: Uncorrected visual acuity was significantly better post-operatively. Most patients reported the surgery met their expectations for decreased dependence on spectacles (93%). Most patients report little or no use of spectacles post-operatively for computer use (93%), distance viewing (93%) and general use throughout the day (87%). A small number of patients report spectacle use for reading (9%) and night driving (18%). There were no relationships detected between demographic variables and visual acuity or patient satisfaction. CONCLUSIONS: Aging of the population presents one of the biggest challenges in the health sector, which includes a rising number of individuals with chronic vision impairment and increased demand for accessible treatment strategies. Cataract surgery with pseudophakic mini-monovision results in high patient satisfaction and considerable reduction in spectacle dependence. Pseudophakic mini-monovision technique is a low-cost, valuable option for patients who would like to reduce dependence on spectacles post-operatively and should be considered along with premium multifocal IOLs in options available for patients based on their needs, preferences and clinical indicators. Reducing spectacle dependence with the pseudophakic mini-monovision technique could improve the functionality, independence and quality of life for many patients who are unsuitable or are unable to pay additional fees associated with premium multifocal IOLs.

Host attachment and fluid shear are integrated into a mechanical signal regulating virulence in Escherichia coli O157:H7.

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. EHEC colonizes the intestinal tract through a range of virulence factors encoded by the locus of enterocyte effacement (LEE), as well as Shiga toxin. Although the factors involved in colonization and disease are well characterized, how EHEC regulates its expression in response to a host encounter is not well understood. Here, we report that EHEC perceives attachment to host cells as a mechanical cue that leads to expression of LEE-encoded virulence genes. This signal is transduced via the LEE-encoded global regulator of LEE-encoded regulator (Ler) and global regulator of Ler and is further enhanced by levels of shear force similar to peristaltic forces in the intestinal tract. Our data suggest that, in addition to a range of chemical environmental signals, EHEC is capable of sensing and responding to mechanical cues to adapt to its host's physiology.

Allelopathic effects of exogenous phenylalanine: a comparison of four monocot species.

MAIN CONCLUSION: Exogenous phenylalanine stunted annual ryegrass but not switchgrass or winter grain rye, with deuterium incorporation up to 3% from phenyalanine-d 8 . Toxicity to duckweed varied with illumination intensity and glucose uptake. Isotopic labeling of biomolecules through biosynthesis from deuterated precursors has successfully been employed for both structural studies and metabolic analysis. Phenylalanine is the precursor of many products synthesized by plants, including the monolignols used for synthesis of lignin. Possible allelochemical effects of phenylalanine have not been reported, although its deamination product cinnamic acid is known to have deleterious effects on root elongation and growth of several plant species. The effects of phenylalanine and its deuterated analog phenylalanine-d 8 added to growth media were studied for annual ryegrass (Lolium multiflorum), winter grain rye (Secale cereale), and switchgrass (Panicum virgatum) cultivated under hydroponic conditions. Growth of annual ryegrass was inhibited by phenylalanine while switchgrass and rye were not significantly affected. Growth was less affected by deuterated phenylalanine-d 8 than by its protiated counterpart, which may be a typical deuterium kinetic isotope effect resulting in slower enzymatic reaction rates. Deuterium incorporation levels of 2-3% were achieved in biomass of switchgrass and annual ryegrass. Both protiated and deuterated phenylalanine were moderately toxic (IC25 values 0.6 and 0.8 mM, respectively) to duckweed (Lemna minor) grown using a 12 h diurnal cycle under photoautotrophic conditions. A significant increase in toxicity, greater for the deuterated form, was noted when duckweed was grown under higher intensity, full spectrum illumination with a metal halide lamp compared to fluorescent plant growth lamps emitting in the blue and red spectral regions. Supplementation with glucose increased toxicity of phenylalanine consistent with synergy between hexose and amino acid uptake that has been reported for duckweed.

Replacement of GroEL in Escherichia coli by the Group II Chaperonin from the Archaeon Methanococcus maripaludis.

UNLABELLED: Chaperonins are required for correct folding of many proteins. They exist in two phylogenetic groups: group I, found in bacteria and eukaryotic organelles, and group II, found in archaea and eukaryotic cytoplasm. The two groups, while homologous, differ significantly in structure and mechanism. The evolution of group II chaperonins has been proposed to have been crucial in enabling the expansion of the proteome required for eukaryotic evolution. In an archaeal species that expresses both groups of chaperonins, client selection is determined by structural and biochemical properties rather than phylogenetic origin. It is thus predicted that group II chaperonins will be poor at replacing group I chaperonins. We have tested this hypothesis and report here that the group II chaperonin from Methanococcus maripaludis (Mm-cpn) can partially functionally replace GroEL, the group I chaperonin of Escherichia coli Furthermore, we identify and characterize two single point mutations in Mm-cpn that have an enhanced ability to replace GroEL function, including one that allows E. coli growth after deletion of the groEL gene. The biochemical properties of the wild-type and mutant Mm-cpn proteins are reported. These data show that the two groups are not as functionally diverse as has been thought and provide a novel platform for genetic dissection of group II chaperonins. IMPORTANCE: The two phylogenetic groups of the essential and ubiquitous chaperonins diverged approximately 3.7 billion years ago. They have similar structures, with two rings of multiple subunits, and their major role is to assist protein folding. However, they differ with regard to the details of their structure, their cofactor requirements, and their reaction cycles. Despite this, we show here that a group II chaperonin from a methanogenic archaeon can partially substitute for the essential group I chaperonin GroEL in E. coli and that we can easily isolate mutant forms of this chaperonin with further improved functionality. This is the first demonstration that these two groups, despite the long time since they diverged, still overlap significantly in their functional properties.

Less with More: Hospitalization Cost and Event Rates with Quadripolar versus Bipolar CRT-D System.

BACKGROUND: This is a comparative effectiveness study for cardiac resynchronization therapy defibrillator (CRT-D) therapy enabled by quadripolar (QUAD) versus bipolar (BIP) left ventricular (LV) leads.  Heart failure (HF) hospitalization (HFH) rates, associated costs, and 30-day readmissions after index HFH were compared. METHODS: Patients with de novo LV leads implanted as part of a CRT-D system between January 2011 and August 2013 with ≥1-year follow-up were included. Medical history, dates, and locations of HFH were collected thereafter. Patients were divided based on LV lead model: QUAD or BIP. Universal billing records (UB-04) for each HFH and ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnoses/procedure codes were used to classify hospitalizations as HF or non-HF and calculate concurrent U.S. national-average medicare reimbursement. Rates, associated payer costs, and 30-day readmissions were then compared using nonparametric bootstrapping. RESULTS: Baseline characteristics (N = 69 QUAD and N = 56 BIP) were similar. The inpatient HFH for the QUAD group (0.20/patient-year) was lower than the BIP group (0.31/patient-year, incidence rate ratio [IRR] = 0.62, P = 0.036). The overall HFH rate for the inpatient or outpatient setting for QUAD (0.29/patient-year) was lower than the BIP group (0.42/patient-year, IRR = 0.69, P = 0.055). Average cost of HFH in QUAD ($4,428/patient-year) was lower than BIP ($7,354/patient-year), a 39.8% cost reduction (P = 0.026). The 30-day readmission rate was also lower in QUAD compared to BIP (19% vs 28%, IRR = 0.68, P = 0.18). CONCLUSION: This U.S. economic comparative study demonstrated that QUAD exhibited lower postimplant inpatient HFH rates and reduced healthcare utilization compared to BIP systems.

Production of deuterated switchgrass by hydroponic cultivation.

MAIN CONCLUSION: The bioenergy crop switchgrass was grown hydroponically from tiller cuttings in 50 % D 2 O to obtain biomass with 34 % deuterium substitution and physicochemical properties similar to those of H 2 O-grown switchgrass controls. Deuterium enrichment of biological materials can potentially enable expanded experimental use of small angle neutron scattering (SANS) to investigate molecular structural transitions of complex systems such as plant cell walls. Two key advances have been made that facilitate cultivation of switchgrass, an important forage and biofuel crop, for controlled isotopic enrichment: (1) perfusion system with individual chambers and (2) hydroponic growth from tiller cuttings. Plants were grown and maintained for several months with periodic harvest. Photosynthetic activity was monitored by measurement of CO2 in outflow from the growth chambers. Plant morphology and composition appeared normal compared to matched controls grown with H2O. Using this improved method, gram quantities of switchgrass leaves and stems were produced by continuous hydroponic cultivation using growth medium consisting of basal mineral salts in 50 % D2O. Deuterium incorporation was confirmed by detection of the O-D and C-D stretching peaks with FTIR and quantified by (1)H- and (2)H-NMR. This capability to produce deuterated lignocellulosic biomass under controlled conditions will enhance investigation of cell wall structure and its deconstruction by neutron scattering and NMR techniques.

The structure of irisin reveals a novel intersubunit ß-sheet fibronectin type III (FNIII) dimer: implications for receptor activation.

Irisin was recently identified as a putative myokine that is induced by exercise. Studies suggest that it is produced by cleavage of the FNDC5 (fibronectin domain-containing protein 5) receptor; irisin corresponds to the extracellular receptor ectodomain. Data suggesting that irisin stimulates white-to-brown fat conversion have led to the hypothesis that it does so by binding an unknown receptor, thus functioning as a myokine. As brown fat promotes energy dissipation, myokines that elicit the transformation of white to brown fat have potentially profound benefits in the treatment of obesity and metabolic disorders. Understanding the molecular basis for such exercise-induced phenomena is thus of considerable interest. Moreover, FNDC5-like receptors are highly conserved and have been shown to be critical for neuronal development. However, the structural and molecular mechanisms utilized by these proteins are currently unknown. Here, we describe the crystal structure and biochemical characterization of the FNDC5 ectodomain, corresponding to the irisin myokine. The 2.28 Å structure shows that irisin consists of an N-terminal fibronectin III (FNIII)-like domain attached to a flexible C-terminal tail. Strikingly, the FNIII-like domain forms a continuous intersubunit ß-sheet dimer, previously unobserved for any FNIII protein. Biochemical data confirm that irisin is a dimer and that dimerization is unaffected by glycosylation. This finding suggests a possible mechanism for receptor activation by the irisin domain as a preformed myokine dimer ligand or as a paracrine or autocrine dimerization module on FNDC5-like receptors.

Preanesthesia medical evaluation for electroconvulsive therapy: a review of the literature.

OBJECTIVE: Electroconvulsive therapy (ECT) is widely used for the treatment of psychiatric disorders, yet there is few published literature to guide the practitioner in the preprocedural evaluation of patients. Based on a review of the literature, we sought to develop a concise, algorithmic approach to be used when evaluating patients for ECT, including those with underlying conditions, such as cardiovascular and neurological disorders. METHODS: The databases of Ovid MEDLINE, PubMed, the Web of Knowledge, and PsychINFO were searched from January 2000 through December 2011. All abstracts were reviewed for relevancy to preprocedural ECT evaluation, and full articles of selected abstracts were reviewed in full, along with bibliographies of each. Algorithms were then constructed using the clinical information obtained from the selected articles. RESULTS: Our review of the literature located 275 articles using the search criteria. After review, 38 articles were selected. A total of 167 articles were excluded because they did not pertain to medical comorbidities in patients undergoing ECT, and an additional 70 were excluded because they did not pertain to ECT. Bibliography review of the selected articles located an additional 10 articles. CONCLUSIONS: Although ECT is generally a safe and effective therapy, some patient subgroups, such as those with certain cardiac conditions or history of cerebrovascular disease, require additional evaluation or, rarely, postponement of ECT. Chronic medical conditions should be optimized before undergoing ECT. Most patient populations are able to undergo ECT safely and effectively.

Statins Restore Endothelial Protection against Complement Activity in Obstructive Sleep Apnea: A Randomized Clinical Trial.

Rationale: Increased cardiovascular risk in obstructive sleep apnea (OSA) persists after continuous positive airway pressure (CPAP) and alternative therapies are needed. Impaired endothelial protection against complement is a cholesterol-dependent process that initiates endothelial inflammation in OSA, which increases cardiovascular risk. Objectives: To investigate directly whether lowering cholesterol improves endothelial protection against complement and its proinflammatory effects in OSA. Methods: Newly diagnosed patients with OSA (n = 87) and OSA-free controls (n = 32) participated. Endothelial cells and blood were collected at baseline, after 4 weeks of CPAP therapy, and again after 4 weeks of 10 mg atorvastatin versus placebo using a randomized, double-blind, parallel-group design. Primary outcome was the proportion of a complement inhibitor, CD59, on the endothelial cell plasma membrane in OSA patients after 4 weeks of statins versus placebo. Secondary outcomes were complement deposition on endothelial cells and circulating levels of its downstream proinflammatory factor, angiopoietin-2, after statins versus placebo. Results: Baseline expression of CD59 was lower, whereas complement deposition on endothelial cells and levels of angiopoietin-2 were greater, in patients with OSA compared with controls. CPAP did not affect expression of CD59 or complement deposition on endothelial cells in patients with OSA, regardless of adherence. Compared with placebo, statins increased expression of endothelial complement protector CD59 and lowered complement deposition in patients with OSA. Good CPAP adherence was associated with increased angiopoietin-2 levels, which was reversed by statins. Conclusions: Statins restore endothelial protection against complement and reduce its downstream proinflammatory effects, suggesting a potential approach to reduce residual cardiovascular risk after CPAP in patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT03122639).

Mild sleep restriction increases endothelial oxidative stress in female persons.

Sleep restriction is associated with increased cardiovascular risk, which is more pronounced in female than male persons. We reported recently first causal evidence that mild, prolonged sleep restriction mimicking "real-life" conditions impairs endothelial function, a key step in the development and progression of cardiovascular disease, in healthy female persons. However, the underlying mechanisms are unclear. In model organisms, sleep restriction increases oxidative stress and upregulates antioxidant response via induction of the antioxidant regulator nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Here, we assessed directly endothelial cell oxidative stress and antioxidant responses in healthy female persons (n = 35) after 6 weeks of mild sleep restriction (1.5 h less than habitual sleep) using randomized crossover design. Sleep restriction markedly increased endothelial oxidative stress without upregulating antioxidant response. Using RNA-seq and a predicted protein-protein interaction database, we identified reduced expression of endothelial Defective in Cullin Neddylation-1 Domain Containing 3 (DCUN1D3), a protein that licenses Nrf2 antioxidant responses, as a mediator of impaired endothelial antioxidant response in sleep restriction. Thus, sleep restriction impairs clearance of endothelial oxidative stress that over time increases cardiovascular risk.Trial Registration: NCT02835261 .

Untangling the threads of cellulose mercerization.

Naturally occurring plant cellulose, our most abundant renewable resource, consists of fibers of long polymer chains that are tightly packed in parallel arrays in either of two crystal phases collectively referred to as cellulose I. During mercerization, a process that involves treatment with sodium hydroxide, cellulose goes through a conversion to another crystal form called cellulose II, within which every other chain has remarkably changed direction. We designed a neutron diffraction experiment with deuterium labelling in order to understand how this change of cellulose chain direction is possible. Here we show that during mercerization of bacterial cellulose, chains fold back on themselves in a zigzag pattern to form crystalline anti-parallel domains. This result provides a molecular level understanding of one of the most widely used industrial processes for improving cellulosic materials.

Complement promotes endothelial von Willebrand factor and angiopoietin-2 release in obstructive sleep apnea.

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) is highly prevalent and triples vascular thromboembolic risk. Intermittent hypoxia (IH) during transient cessation of breathing in OSA impairs endothelial protection against complement. Complement activation stimulates the endothelial release of a pro-thrombotic von Willebrand factor (vWF). We investigated whether increased complement activity in OSA promotes the endothelial release of vWF and pro-inflammatory angiopoietin-2. We further investigated whether improving complement protection with statins reverses these changes. METHODS: Using endothelial cells (ECs) and blood collected from OSA patients (n = 109) and controls (n = 67), we assessed whether altered cellular localization of complement inhibitor CD59 in OSA modulates exocytosis of Weibel-Palade bodies (WPB), secretory granules that store vWF and angiopoietin-2. These interactions were also assessed in vitro in ECs exposed to normoxia or IH with or without recombinant complement C9 and with or without atorvastatin. RESULTS: Circulating levels of angiopoietin-2 were greater in OSA than controls and levels of vWF cleavage products correlated with OSA severity. In cultured ECs, IH enhanced complement-stimulated angiopoietin-2 and vWF release by reducing EC surface and increasing intracellular expression of complement inhibitor CD59. Intracellular CD59 co-localized with WPB in OSA. IH increased binding of intracellular CD59 to syntaxin-3, which dissociated syntaxin-3 from voltage-sensitive calcium channel Cav1.2, and activated WPB exocytosis in a calcium-dependent manner. Atorvastatin reversed IH-enhanced endothelial release of vWF and angiopoietin-2. CONCLUSIONS: IH promotes the complement-mediated release of vWF and angiopoietin-2, which may contribute to pro-thrombotic and pro-inflammatory conditions in OSA. Statin reversed these effects, suggesting a potential approach to reduce cardiovascular risk in OSA.

Cellulose-lignin composite fibres as precursors for carbon fibres. Part 1 - Manufacturing and properties of precursor fibres.

Cellulose-lignin composite fibres were spun from ionic liquid (IL) solutions by dry-jet wet spinning. Birch pre-hydrolysed Kraft (PHK) pulp and organosolv beech (BL) or spruce lignin (SL) were dissolved in the IL 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH]OAc) to prepare spinning dopes. Fibres with lignin concentrations of up to 50 % were spun successfully. The fibres were analysed focusing on important properties for the production of carbon fibres (CF). Due to the higher molar mass of the SL compared to the BL, SL showed higher stability in the spinning process, giving higher lignin content in the final fibres. The CF yield after carbonization increased with increasing lignin content. The higher carbon content of SL compared to BL, resulted in moderately higher CF yield of the SL fibres, compared to fibres with BL. Overall, the produced cellulose-lignin composite fibres show great potential as precursors for CF production.