Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study.

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial.

The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5-35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results.

Anhydride-functional silane immobilized onto titanium surfaces induces osteoblast cell differentiation and reduces bacterial adhesion and biofilm formation.

Bacterial infection in dental implants along with osseointegration failure usually leads to loss of the device. Bioactive molecules with antibacterial properties can be attached to titanium surfaces with anchoring molecules such as silanes, preventing biofilm formation and improving osseointegration. Properties of silanes as molecular binders have been thoroughly studied, but research on the biological effects of these coatings is scarce. The aim of the present study was to determine the in vitro cell response and antibacterial effects of triethoxysilypropyl succinic anhydride (TESPSA) silane anchored on titanium surfaces. X-ray photoelectron spectroscopy confirmed a successful silanization. The silanized surfaces showed no cytotoxic effects. Gene expression analyses of Sarcoma Osteogenic (SaOS-2) osteoblast-like cells cultured on TESPSA silanized surfaces reported a remarkable increase of biochemical markers related to induction of osteoblastic cell differentiation. A manifest decrease of bacterial adhesion and biofilm formation at early stages was observed on treated substrates, while favoring cell adhesion and spreading in bacteria-cell co-cultures. Surfaces treated with TESPSA could enhance a biological sealing on implant surfaces against bacteria colonization of underlying tissues. Furthermore, it can be an effective anchoring platform of biomolecules on titanium surfaces with improved osteoblastic differentiation and antibacterial properties.

MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts.

SCOPE: MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients. METHODS AND RESULTS: We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes. CONCLUSION: PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research.

Antibacterial coatings on titanium surfaces: a comparison study between in vitro single-species and multispecies biofilm.

Dental plaque is a biofilm that causes dental caries, gingivitis, and periodontitis. Most of the studies in antibacterial coatings have been conducted by in vitro single-species biofilm formation, but oral biofilm involves more than 700 different bacterial species that are able to interact. Therefore, new studies are focused on in vitro multispecies biofilm models that mimic in vivo biofilms. The aim of the present work was to study different antibacterial coatings onto titanium surfaces and evaluate the in vitro antimicrobial properties of the surfaces on two different bacterial species and an oral biofilm. The lactate dehydrogenase assay determined that treated samples did not affect fibroblast viability. In addition, the viability of microorganisms on modified samples was evaluated by a LIVE/DEAD BacLight bacterial viability kit. Although a decrease in viable bacteria onto treated samples was obtained, the results showed differences in effectiveness when single-biofilm and oral plaque were tested. It confirms, as we expected, the distinct sensitivities that bacterial strains have. Thus, this multispecies biofilms model holds a great potential to assess antibacterial properties onto samples for dental purposes.

Antibacterial properties of hLf1-11 peptide onto titanium surfaces: a comparison study between silanization and surface initiated polymerization.

Dental implant failure can be associated with infections that develop into peri-implantitis. In order to reduce biofilm formation, several strategies focusing on the use of antimicrobial peptides (AMPs) have been studied. To covalently immobilize these molecules onto metallic substrates, several techniques have been developed, including silanization and polymer brush prepared by surface-initiated atom transfer radical polymerization (ATRP), with varied peptide binding yield and antibacterial performance. The aim of the present study was to compare the efficiency of these methods to immobilize the lactoferrin-derived hLf1-11 antibacterial peptide onto titanium, and evaluate their antibacterial activity in vitro. Smooth titanium samples were coated with hLf1-11 peptide under three different conditions: silanization with 3-aminopropyltriethoxysilane (APTES), and polymer brush based coatings with two different silanes. Peptide presence was determined by X-ray photoelectron spectroscopy, and the mechanical stability of the coatings was studied under ultrasonication. The LDH assays confirmed that HFFs viability and proliferation were no affected by the treatments. The in vitro antibacterial properties of the modified surfaces were tested with two oral strains (Streptococcus sanguinis and Lactobacillus salivarius) showing an outstanding reduction. A higher decrease in bacterial attachment was noticed when samples were modified by ATRP methods compared to silanization. This effect is likely due to the capacity to immobilize more peptide on the surfaces using polymer brushes and the nonfouling nature of polymer PDMA segment.

Covalent immobilization of hLf1-11 peptide on a titanium surface reduces bacterial adhesion and biofilm formation.

Bacterial infection represents a major cause of implant failure in dentistry. A common approach to overcoming this issue and treating peri-implant infection consists in the use of antibiotics. However, the rise of multidrug-resistant bacteria poses serious concerns to this strategy. A promising alternative is the use of antimicrobial peptides due to their broad-spectrum activity against bacteria and reduced bacterial resistance responses. The aim of the present study was to determine the in vitro antibacterial activity of the human lactoferrin-derived peptide hLf1-11 anchored to titanium surfaces. To this end, titanium samples were functionalized with the hLf1-11 peptide either by silanization methods or physical adsorption. X-ray photoelectron spectroscopy analyses confirmed the successful covalent attachment of the hLf1-11 peptide onto titanium surfaces. Lactate dehydrogenase assay determined that hLf1-11 peptide did not affect fibroblast viability. An outstanding reduction in the adhesion and early stages of biofilm formation of Streptococcus sanguinis and Lactobacillus salivarius was observed on the biofunctionalized surfaces compared to control non-treated samples. Furthermore, samples coated with the hLf1-11 peptide inhibited the early stages of bacterial growth. Thus, this strategy holds great potential to develop antimicrobial biomaterials for dental applications.

Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients.

SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS: CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.

Seasonal and sex-related variations in serum steroid hormone levels in wild and farmed brown trout Salmo trutta L. in the north-west of Spain.

Serum steroid profiles were investigated in order to evaluate the potential use of circulating sex steroid levels as a tool for sex identification in brown trout. Changes in the serum concentrations of testosterone (T), progesterone (P), 17-ß-estradiol (E2), and cortisol (F) in wild and farmed mature female and male brown trout, Salmo trutta L., were measured in each season (January, May, July, and October) in six rivers and four hatcheries located in the north-west of Spain. Serum cortisol levels in farmed brown trout were significantly higher and showed a seasonal pattern opposite to that found in wild trout. Because levels of the hormones under study can be affected by disruptive factors such as exposure to phytoestrogens (which alters the hypothalamic-pituitary-gonadal axis) and infection with Saprolegnia parasitica (which alters the hypothalamic-pituitary-adrenal axis), both factors are taken into account.

A low elastic modulus Ti-Nb-Hf alloy bioactivated with an elastin-like protein-based polymer enhances osteoblast cell adhesion and spreading.

ß-type titanium alloys with low Young's modulus are desirable to reduce stress shielding effect and enhance bone remodeling for implants used to substitute failed hard tissue. For biomaterials application, the surface bioactivity is necessary to achieve optimal osseointegration. In the previous work, the low elastic modulus (43 GPa) Ti-25Nb-16Hf (wt %) alloy was mechanically and microstructurally characterized. In the present work, the biological behavior of Ti-25Nb-16Hf was studied. The biological response was improved by surface modification. The metal surface was modified by oxygen plasma and subsequently silanized with 3-chloropropyl(triethoxy)silane for covalent immobilization of the elastin-like polymer. The elastin-like polymer employed exhibits RGD bioactive motives inspired to the extracellular matrix in order to improve cell adhesion and spreading. Upon modification, the achieved surface presented different physical and chemical properties, such as surface energy and chemical composition. Subsequently, osteoblast adhesion, cell numbers, and differentiation studies were performed to correlate surface properties and cell response. The general tendency was that the higher surface energy the higher cell adhesion. Furthermore, cell culture and immunofluorescence microscopy images demonstrated that RGD-modified surfaces improved adhesion and spreading of the osteoblast cell type.

Mechanical properties of organically modified silicates for bone regeneration.

In this paper, different organic-inorganic hybrid materials based in the CaO-SiO(2)-poly(dimethyl siloxane) PDMS system have been characterised by means of nanoindentation and their static mechanical properties (Young's modulus, and hardness) have been investigated. These mechanical properties have been discussed in relation to the chemical composition and structure of the different hybrid materials. Besides, the mechanical behaviour of hybrid materials is visco-elastic and it therefore presents phenomena of creep that will be influenced by the temperature of the mechanical test; undoubtedly, a temperature of 37 degrees C accelerates the processes of creep.

Aging of retrieved zirconia femoral heads.

Yttria-stabilized tetragonal zirconia may undergo extensive transformation to the monoclinic phase under mechanical and/or hydrothermal stress, with degradation of mechanical and tribologic properties. We hypothesized progressive phase transformation of zirconia in service in vivo is directly related to the time of implantation and to patient-related factors. The subsequent decrease in fracture toughness and increase in surface roughness and wear are related to the increased monoclinic content. We performed a study on 47 yttria-stabilized tetragonal zirconia femoral heads retrieved from failed total hip arthroplasties after 2 to 10 years implantation. Age, weight, and activity of the patients were retrieved from clinical records. Monoclinic content, fracture toughness, surface roughness, and wear were measured. Strong correlations were found between monoclinic content in the weightbearing surface and time of implantation (r = 0.97) and between increase in monoclinic content and decrease in fracture toughness (r = -0.92), increase in surface roughness (r = 0.88), and increase in surface wear (r = 0.89). No correlation was observed between the increase in monoclinic content and the age, weight, or activity of the patients. Aging of zirconia in vivo is then a function of time in service, and the loss of surface properties is caused by the corresponding increase in monoclinic content.

Characterization of nasal paraffinoma following septorhinoplasty by attenuated total reflection--fourier transform infrared spectroscopy (ATR-FTIR).

Vaseline and paraffin have been injected into various parts of the body. Vaselinoma and paraffinoma are well-described complications, despite which nasal packing with Vaseline gauze is still common in the management of epistaxis, after rhinoplasty, endonasal surgery, to control bleeding and prevent synechiae or restenosis. Our aim is to highlight this complication, propose a safe method for its diagnosis and establish guidelines for its prevention. We report two cases of paraffinoma occurring after rhinoplasty and discuss prevention of this rare but serious complication, and suggest an alternative dressing. Attenuated total reflection (ATR) FI7R spectra have proven to be a definitive characterising tool for surgical extracts, guaranteeing detection of mineral products that histology does not offer. For these lesions we propose the name "petroleum oilomas" which we feel to be more appropriate than the more commonly used paraffinomas. Relevance of the work: a description of an innovative and safe method of diagnosis, and proposal of a procedure for postrhinoplasty packing (without mineral oils) to avoid this complication.