Characterization of Stealth Liposome-Based Nanoparticles Encapsulating the ACAT1/SOAT1 Inhibitor F26: Efficacy and Toxicity Studies In Vitro and in Wild-Type Mice.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme responsible for catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high-affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer's disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. The results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs), and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

Markers of Biological Brain Aging Mediate Effects of Vascular Risk Factors on Cognitive and Motor Functions: A Multivariate Imaging Analysis of 40,579 Individuals.

The increasing global life expectancy brings forth challenges associated with age-related cognitive and motor declines. To better understand underlying mechanisms, we investigated the connection between markers of biological brain aging based on magnetic resonance imaging (MRI), cognitive and motor performance, as well as modifiable vascular risk factors, using a large-scale neuroimaging analysis in 40,579 individuals of the population-based UK Biobank and Hamburg City Health Study. Employing partial least squares correlation analysis (PLS), we investigated multivariate associative effects between three imaging markers of biological brain aging - relative brain age, white matter hyperintensities of presumed vascular origin, and peak-width of skeletonized mean diffusivity - and multi-domain cognitive test performances and motor test results. The PLS identified a latent dimension linking higher markers of biological brain aging to poorer cognitive and motor performances, accounting for 94.7% of shared variance. Furthermore, a mediation analysis revealed that biological brain aging mediated the relationship of vascular risk factors - including hypertension, glucose, obesity, and smoking - to cognitive and motor function. These results were replicable in both cohorts. By integrating multi-domain data with a comprehensive methodological approach, our study contributes evidence of a direct association between vascular health, biological brain aging, and functional cognitive as well as motor performance, emphasizing the need for early and targeted preventive strategies to maintain cognitive and motor independence in aging populations.

Standardization via Post Column Infusion-A Novel and Convenient Quantification Approach for LC-MS/MS.

Mass spectrometry (MS) is a widely used analytical technique including medical diagnostics, forensic toxicology, food and water analysis. The gold standard for quantifying compounds involves using stable isotope-labeled internal standards (SIL-IS). However, when these standards are not commercially available, are prohibitively expensive, or are extremely difficult to synthesize, alternative external quantification techniques are employed. We hereby present a novel, convenient and cheap quantification approach-quantification via post column infusion (PCI). As a proof of concept, we demonstrated PCI quantification for the immunosuppressant tacrolimus in whole blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The validation results met the criteria according to the guideline on bioanalytical method validation of the European Medicine Agency (EMA), achieving imprecisions and inaccuracies with coefficient of variation and relative bias below 15%. Anonymized and leftover whole blood samples from immunosuppressed patients receiving tacrolimus were used for method comparison (PCI quantification vs. conventional internal standard (IS) quantification). Both methods showed strong agreement with a Pearson correlation coefficient of r = 0.9532. This novel PCI quantification technique (using the target analyte itself) expands the quantification options available in MS, providing reliable results, particularly when internal standards are unavailable or unaffordable. With the current paper, we aim to demonstrate that our innovative PCI technique has great potential to overcome practical issues in quantification and to provide guidance on how to incorporate PCI in existing or new LC-MS methods. Moreover, this study demonstrated a more convenient method for correcting matrix effects in comparison to alternative PCI techniques.

Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb® in Patients with Hyperinflammation: A Prospective Study.

INTRODUCTION: The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far. METHODS: The prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients' blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: b l o o d f l o w ∗ c o n c e n t r a t i o n p r e - p o s t c o n c e n t r a t i o n pre . RESULTS: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70-100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p < 0.05) decrease in the blood concentration after 6 h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230 pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252 pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0 pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487 pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4 pg/ml), interleukin 10 (median 88 vs. 56 pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104 pg/ml). A significant (p < 0.05) decrease in patients' blood after 12 h was only detected for interleukin 10. CONCLUSIONS: CS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04913298, registration date June 4, 2021.

Mapping the interplay of atrial fibrillation, brain structure, and cognitive dysfunction.

INTRODUCTION: Atrial fibrillation (AF) is associated with an elevated risk of cognitive impairment and dementia. Understanding the cognitive sequelae and brain structural changes associated with AF is vital for addressing ensuing health care needs. METHODS AND RESULTS: We examined 1335 stroke-free individuals with AF and 2683 matched controls using neuropsychological assessments and multimodal neuroimaging. The analysis revealed that individuals with AF exhibited deficits in executive function, processing speed, and reasoning, accompanied by reduced cortical thickness, elevated extracellular free-water content, and widespread white matter abnormalities, indicative of small vessel pathology. Notably, brain structural differences statistically mediated the relationship between AF and cognitive performance. DISCUSSION: Integrating a comprehensive analysis approach with extensive clinical and magnetic resonance imaging data, our study highlights small vessel pathology as a possible unifying link among AF, cognitive decline, and abnormal brain structure. These insights can inform diagnostic approaches and motivate the ongoing implementation of effective therapeutic strategies. Highlights We investigated neuropsychological and multimodal neuroimaging data of 1335 individuals with atrial fibrillation (AF) and 2683 matched controls. Our analysis revealed AF-associated deficits in cognitive domains of attention, executive function, processing speed, and reasoning. Cognitive deficits in the AF group were accompanied by structural brain alterations including reduced cortical thickness and gray matter volume, alongside increased extracellular free-water content as well as widespread differences of white matter integrity. Structural brain changes statistically mediated the link between AF and cognitive performance, emphasizing the potential of structural imaging markers as a diagnostic tool in AF-related cognitive decline.

Reduced olfactory bulb volume accompanies olfactory dysfunction after mild SARS-CoV-2 infection.

Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Open-source machine learning pipeline automatically flags instances of acute respiratory distress syndrome from electronic health records.

Physicians could greatly benefit from automated diagnosis and prognosis tools to help address information overload and decision fatigue. Intensive care physicians stand to benefit greatly from such tools as they are at particularly high risk for those factors. Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition affecting >10% of critical care patients and has a mortality rate over 40%. However, recognition rates for ARDS have been shown to be low (30-70%) in clinical settings. In this work, we present a reproducible computational pipeline that automatically adjudicates ARDS on retrospective datasets of mechanically ventilated adult patients. This pipeline automates the steps outlined by the Berlin Definition through implementation of natural language processing tools and classification algorithms. We train an XGBoost model on chest imaging reports to detect bilateral infiltrates, and another on a subset of attending physician notes labeled for the most common ARDS risk factor in our data. Both models achieve high performance-a minimum area under the receiver operating characteristic curve (AUROC) of 0.86 for adjudicating chest imaging reports in out-of-bag test sets, and an out-of-bag AUROC of 0.85 for detecting a diagnosis of pneumonia. We validate the entire pipeline on a cohort of MIMIC-III encounters and find a sensitivity of 93.5% - an extraordinary improvement over the 22.6% ARDS recognition rate reported for these encounters - along with a specificity of 73.9%. We conclude that our reproducible, automated diagnostic pipeline exhibits promising accuracy, generalizability, and probability calibration, thus providing a valuable resource for physicians aiming to enhance ARDS diagnosis and treatment strategies. We surmise that proper implementation of the pipeline has the potential to aid clinical practice by facilitating the recognition of ARDS cases at scale.

Optimizing the Extraction of Bioactive Compounds from Porphyra linearis (Rhodophyta): Evaluating Alkaline and Enzymatic Hydrolysis for Nutraceutical Applications.

Porphyra sensu lato is one of the most economically significant and widely cultured and consumed algae in the world. Porphyra species present excellent nutraceutic properties due to their bioactive compounds (BACs). This research aimed to find the most efficient aqueous extraction method for BACs by examining alkaline and enzymatic hydrolysis. Alkaline hydrolysis with 2.5% sodium carbonate (SC) and at 80 °C proved optimal for extracting all BACs (phycobiliproteins, soluble proteins, polyphenols, and carbohydrates) except mycosporine-like amino acids (MAAs), which were best extracted with water only, and at 80 °C. Enzymatic hydrolysis, particularly with the 'Miura' enzymatic cocktail (cellulase, xylanase, glycoside hydrolase, and ß-glucanase), showed superior results in extracting phycoerythrin (PE), phycocyanin (PC), soluble proteins, and carbohydrates, with increases of approximately 195%, 510%, 890%, and 65%, respectively, compared to the best alkaline hydrolysis extraction (2.5% SC and 80 °C). Phenolic content analysis showed no significant difference between the 'Miura' cocktail and 2.5% SC treatments. Antioxidant activity was higher in samples from alkaline hydrolysis, while extraction of MAAs showed no significant difference between water-only and 'Miura' treatments. The study concludes that enzymatic hydrolysis improves the efficiency of BACs extraction in P. linearis, highlighting its potential for the nutraceutical industry, and especially with respect to MAAs for topical and oral UV-photoprotectors.

Quantitative proteomics reveals cellular responses to individual mAb expression and tunicamycin in CHO cells.

Chinese hamster ovary (CHO) cells are popular in the pharmaceutical industry for their ability to produce high concentrations of antibodies and their resemblance to human cells in terms of protein glycosylation patterns. Current data indicate the relevance of CHO cells in the biopharmaceutical industry, with a high number of product commendations and a significant market share for monoclonal antibodies. To enhance the production capabilities of CHO cells, a deep understanding of their cellular and molecular composition is crucial. Genome sequencing and proteomic analysis have provided valuable insights into the impact of the bioprocessing conditions, productivity, and product quality. In our investigation, we conducted a comparative analysis of proteomic profiles in high and low monoclonal antibody-producing cell lines and studied the impact of tunicamycin (TM)-induced endoplasmic reticulum (ER) stress. We examined the expression levels of different proteins including unfolded protein response (UPR) target genes by using label-free quantification techniques for protein abundance. Our results show the upregulation of proteins associated with protein folding mechanisms in low producer vs. high producer cell line suggesting a form of ER stress related to specific protein production. Further, Hspa9 and Dnaja3 are notable candidates activated by the mitochondria UPR and play important roles in protein folding processes in mitochondria. We identified significant upregulation of Nedd8 and Lgmn proteins in similar levels which may contribute to UPR stress. Interestingly, the downregulation of Hspa5/Bip and Pdia4 in response to tunicamycin treatment suggests a low-level UPR activation. KEY POINTS: • Proteome profiling of recombinant CHO cells under mild TM treatment. • Identified protein clusters are associated with the unfolded protein response (UPR). • The compared cell lines revealed noticeable disparities in protein expression levels.

The Role of Nitrate Supply in Bioactive Compound Synthesis and Antioxidant Activity in the Cultivation of Porphyra linearis (Rhodophyta, Bangiales) for Future Cosmeceutical and Bioremediation Applications.

Porphyra sensu lato has economic importance for food and pharmaceutical industries due to its significant physiological activities resulting from its bioactive compounds (BACs). This study aimed to determine the optimal nitrate dosage required in short-term cultivation to achieve substantial BAC production. A nitrate experiment using varied concentrations (0 to 6.5 mM) revealed optimal nitrate uptake at 0.5 mM in the first two days and at 3 and 5 mM in the last five days. Polyphenols and carbohydrates showed no differences between treatments, while soluble proteins peaked at 1.5 and 3 mM. Total mycosporine-like amino acids (MAAs) were highest in algae incubated at 5 and 6.5 mM, and the highest antioxidant activity was observed in the 5 mM, potentially related to the MAAs amount. Total carbon and sulfur did not differ between treatments, while nitrogen decreased at higher nitrate. This discovery highlights the nuanced role of nitrate in algal physiology, suggesting that biological and chemical responses to nitrate supplementation can optimize an organism's health and its commercially significant bioactive potential. Furthermore, given its ability to absorb high doses of nitrate, this alga can be cultivated in eutrophic zones or even in out-/indoor tanks, becoming an excellent option for integrated multi-trophic aquaculture (IMTA) and bioremediation.

Longitudinal microstructural alterations surrounding subcortical ischemic stroke lesions detected by free-water imaging.

In this study we explore the spatio-temporal trajectory and clinical relevance of microstructural white matter changes within and beyond subcortical stroke lesions detected by free-water imaging. Twenty-seven patients with subcortical infarct with mean age of 66.73 (SD 11.57) and median initial NIHSS score of 4 (IQR 3-7) received diffusion MRI 3-5 days, 1 month, 3 months, and 12 months after symptom-onset. Extracellular free-water and fractional anisotropy of the tissue (FAT) were averaged within stroke lesions and the surrounding tissue. Linear models showed increased free-water and decreased FAT in the white matter of patients with subcortical stroke (lesion [free-water/FAT, mean relative difference in %, ipsilesional vs. contralesional hemisphere at 3-5 days, 1 month, 3 months, and 12 months after symptom-onset]: +41/-34, +111/-37, +208/-26, +251/-18; perilesional tissue [range in %]: +[5-24]/-[0.2-7], +[2-20]/-[3-16], +[5-43]/-[2-16], +[10-110]/-[2-12]). Microstructural changes were most prominent within the lesion and gradually became less pronounced with increasing distance from the lesion. While free-water elevations continuously increased over time and peaked after 12 months, FAT decreases were most evident 1 month post-stroke, gradually returning to baseline values thereafter. Higher perilesional free-water and higher lesional FAT at baseline were correlated with greater reductions in lesion size (rho = -0.51, p = .03) in unadjusted analyses only, while there were no associations with clinical measures. In summary, we find a characteristic spatio-temporal pattern of extracellular and cellular alterations beyond subcortical stroke lesions, indicating a dynamic parenchymal response to ischemia characterized by vasogenic edema, cellular damage, and white matter atrophy.

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial.

BACKGROUND: Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA). METHODS: Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients. RESULTS: Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L. CONCLUSIONS: Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection "lung". Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.

Spinach genomes reveal migration history and candidate genes for important crop traits.

Spinach (Spinacia oleracea) is an important leafy crop possessing notable economic value and health benefits. Current genomic resources include reference genomes and genome-wide association studies. However, the worldwide genetic relationships and the migration history of the crop remained uncertain, and genome-wide association studies have produced extensive gene lists related to agronomic traits. Here, we re-analysed the sequenced genomes of 305 cultivated and wild spinach accessions to unveil the phylogeny and history of cultivated spinach and to explore genetic variation in relation to phenotypes. In contrast to previous studies, we employed machine learning methods (based on Extreme Gradient Boosting, XGBoost) to detect variants that are collectively associated with agronomic traits. Variant-based cluster analyses revealed three primary spinach groups in the Middle East, Asia and Europe/US. Combining admixture analysis and allele-sharing statistics, migration routes of spinach from the Middle East to Europe and Asia are presented. Using XGBoost machine learning models we predict genomic variants influencing bolting time, flowering time, petiole color, and leaf surface texture and propose candidate genes for each trait. This study enhances our understanding of the history and phylogeny of domesticated spinach and provides valuable information on candidate genes for future genetic improvement of the crop.

Single crown restorations supported by 6-mm implants in the resorbed posterior mandible: A 10-year prospective case series.

PURPOSE: To assess marginal bone level changes, implant and restoration survival, condition of the peri-implant mucosa, and the patient's satisfaction with the single restoration supported by a 6-mm long implant in the posterior mandible after 10 years in function. MATERIALS AND METHODS: Twenty-one consecutive patients missing premolars or molars in the posterior mandible, with a bone volume consisting of a width of at least 6 mm and an estimated height of 8 mm between the top of the ridge and alveolar nerve, were included. Each patient received one or more 6-mm implants. After 3 months, the implants were restored with custom-made titanium abutments and cemented zirconia-based porcelain crowns. The clinical examination and radiograph data were assessed at restoration placement and after 12, 60, and 120 months. The patients answered a questionnaire to score their satisfaction before treatment and after 12, 60, and 120 months with the restoration in function. RESULTS: A total of 31 implants were placed. Implant survival was 100%. The 10-year mean marginal bone loss was 0.18 mm (SE: 0.08). The plaque, calculus, gingiva, and bleeding indices scores were low as was the mean pocket probing depth. The patients' satisfaction was high. CONCLUSION: The 10-year follow-up data of this limited case series study reveal that 6-mm dental implants inserted in the resorbed posterior mandible provide a solid basis for single tooth restorations.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition.

The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

Genomic basis of seed colour in quinoa inferred from variant patterns using extreme gradient boosting.

Quinoa is an agriculturally important crop species originally domesticated in the Andes of central South America. One of its most important phenotypic traits is seed colour. Seed colour variation is determined by contrasting abundance of betalains, a class of strong antioxidant and free radicals scavenging colour pigments only found in plants of the order Caryophyllales. However, the genetic basis for these pigments in seeds remains to be identified. Here we demonstrate the application of machine learning (extreme gradient boosting) to identify genetic variants predictive of seed colour. We show that extreme gradient boosting outperforms the classical genome-wide association approach. We provide re-sequencing and phenotypic data for 156 South American quinoa accessions and identify candidate genes potentially controlling betalain content in quinoa seeds. Genes identified include novel cytochrome P450 genes and known members of the betalain synthesis pathway, as well as genes annotated as being involved in seed development. Our work showcases the power of modern machine learning methods to extract biologically meaningful information from large sequencing data sets.

Single crowns in the posterior maxilla supported by either 11-mm long implants with sinus floor augmentation or by 6-mm long implants: A 10-year randomized controlled trial.

OBJECTIVES: To compare the clinical performance of single crowns in the posterior maxilla supported by either 11-mm long implants combined with maxillary sinus floor augmentation (MSFA) surgery or by 6-mm long implants during a 10-year follow-up period. MATERIALS AND METHODS: Subjects were randomly allocated to receive one 11-mm long implant in combination MFSA or to receive one 6-mm long implant without any grafting. Twenty-one implants in 20 patients were placed in the 6-mm group and 20 implants in 18 patients were placed in the 11-mm group. Both groups were followed by clinical and radiographic examinations up to 10 years. Patients' satisfaction was also scored before treatment. RESULTS: Two patients died and eight patients moved during the follow-up. Two patients lost an implant in the 6-mm group and one implant was lost in the 11-mm group (implant survival 89.5% and 90.9%, respectively). From loading to 10 years' follow-up, mean ± SE marginal bone loss in the 6-mm group and 11-mm group was 0.18 ± 0.10 mm and 0.26 ± 0.12 mm, respectively, without a significant difference between the groups at 10 years (p = .650). In both groups, indices scores for plaque, calculus, gingiva and bleeding were low as well as mean pocket probing depth. Patients' satisfaction at 10 years was high in both groups; mean overall satisfaction in the 6-mm group and 11-mm group was 9.6 ± 0.6 and 9.2 ± 0.8, respectively (p = .168). CONCLUSIONS: Placement of 6-mm implants or 11-mm implants combined MFSA are equally successful during a 10-year follow-up period when applied for supporting a single restoration.

Antitumor and antioxidant activities of polysaccharides from the seaweed Durvillaea antarctica.

The present study was carried out to determine the antitumor and antioxidant activities of the seaweed Durvillaea antarctica. Extraction and purification of polysaccharides from D. antarctica were performed. They were characterized by FT-IR and GC-MS, identifying isomers of arabinose, fucose, mannose, and galactose. The antioxidant capacity of polysaccharides was analyzed using the ABTS method (14.3 ± 0.5 µmol TE g-1 PS) and the DPPH method (21.82 ± 0.32 µmol TE g-1 PS). The antitumor capacity of polysaccharides was studied by MTT colorimetric assays in human leukemia, colon, breast, and lung cancer cell lines, obtaining the lowest IC50 in colon cancer (19.99 µg mL-1 ). In the line of healthy human gingival fibroblasts (HGF-1), an IC50 of 444.39 µg mL-1 was obtained. Flow cytometry in the HL60 cell line showed that polysaccharides at concentrations higher than IC50 inhibited cell proliferation, demonstrating a possible antitumor capacity in vitro. In the proteomic analysis with HGF-1, nine proteins involved in different biological processes were identified. In conclusion, polysaccharides from D. antarctica could be considered powerful nutraceuticals, mainly against colon cancer.