Efficient Hydroxyapatite Extraction from Salmon Bone Waste: An Improved Lab-Scaled Physico-Chemico-Biological Process.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods-alkaline hydrolysis, calcination, and NaOH hydrolysis-to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis-calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications.

Similar patient-reported outcomes for hybrid and cemented stem fixation for aseptic tibial revision total knee arthroplasty: a comparison of sequential prospective cohorts.

PURPOSE: The tibial stem fixation in an aseptic revision of total knee arthroplasty is poorly studied and controversial. The objective of this study was to prospectively compare clinical outcomes between hybrid and cemented fixation of the stem in aseptic tibial revision after a minimum follow-up of 5 years. METHODS: Two sequential prospective cohorts of patients who underwent aseptic tibial revision were compared after a minimum follow-up of five years: 31 had both tibial tray and stem cemented (cemented group), and 42 had a hybrid fixation with tibial tray cemented and stem cementless (hybrid group). Clinical assessment was performed by the Knee Society Scores and reduced Western Ontario and McMaster Universities Arthritis Index. Radiological assessment was also performed. RESULTS: There were no significant differences in preoperative data between groups. Postoperatively, no significant differences between groups in clinical scores or complication rate were found. Survival of the TKA revision at 5-year was 94% (95% CI 89-98%) in the cemented group, and 98% (95% CI 92-100%) in the hybrid group (ns). CONCLUSION: Clinical outcomes and implant survival were comparable between hybrid and cemented tibial stem fixation. LEVEL OF EVIDENCE: II.

Cross-sectional associations of impaired glucose metabolism measures with bleeding on probing and periodontitis.

AIM: This study assessed the associations of pre-diabetes and insulin resistance with bleeding on probing (BOP) and periodontitis among adults. MATERIALS AND METHODS: We included 1191 Hispanic adults aged 40-65 years, free of diabetes, enrolled in San Juan Overweight Adults Longitudinal Study. Pre-diabetes was defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired glycated haemoglobin. Impaired one-hour plasma glucose (1hPG) was defined as levels >155 mg/dl. Insulin resistance was defined using the study population-specific 75th percentile (HOMA-IR ≥ 3.13). High BOP was defined as percentage of teeth with bleeding ≥30%. Periodontitis was defined according to the CDC/AAP definition. RESULTS: After multivariable adjustment for age, gender, education, smoking status, alcohol consumption, physical activity, obesity, HDL-C, and plaque index, pre-diabetes with and without 1hPG, IFG, impaired 1hPG, IGT, and HOMA-IR were significantly associated with high BOP; pre-diabetes, IFG, and impaired 1hPG were significantly associated with severe periodontitis. Most of these associations remained significant when the analyses were restricted to non-smokers. CONCLUSIONS: This study suggests associations between pre-diabetes and insulin resistance with BOP and periodontitis. Given the high prevalence of impaired glucose metabolism and periodontitis, the assessment of the temporal sequence of these associations is of utmost importance.

Sucrose synthase activity in the sus1/sus2/sus3/sus4 Arabidopsis mutant is sufficient to support normal cellulose and starch production.

Sucrose synthase (SUS) catalyzes the reversible conversion of sucrose and a nucleoside diphosphate into the corresponding nucleoside diphosphate-glucose and fructose. In Arabidopsis, a multigene family encodes six SUS (SUS1-6) isoforms. The involvement of SUS in the synthesis of UDP-glucose and ADP-glucose linked to Arabidopsis cellulose and starch biosynthesis, respectively, has been questioned by Barratt et al. [(2009) Proc Natl Acad Sci USA 106:13124-13129], who showed that (i) SUS activity in wild type (WT) leaves is too low to account for normal rate of starch accumulation in Arabidopsis, and (ii) different organs of the sus1/sus2/sus3/sus4 SUS mutant impaired in SUS activity accumulate WT levels of ADP-glucose, UDP-glucose, cellulose and starch. However, these authors assayed SUS activity under unfavorable pH conditions for the reaction. By using favorable pH conditions for assaying SUS activity, in this work we show that SUS activity in the cleavage direction is sufficient to support normal rate of starch accumulation in WT leaves. We also demonstrate that sus1/sus2/sus3/sus4 leaves display WT SUS5 and SUS6 expression levels, whereas leaves of the sus5/sus6 mutant display WT SUS1-4 expression levels. Furthermore, we show that SUS activity in leaves and stems of the sus1/sus2/sus3/sus4 and sus5/sus6 plants is ∼85% of that of WT leaves, which can support normal cellulose and starch biosynthesis. The overall data disprove Barratt et al. (2009) claims, and are consistent with the possible involvement of SUS in cellulose and starch biosynthesis in Arabidopsis.

The blood-brain barrier: structure, function and therapeutic approaches to cross it.

The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.

Similar survival between screw cementless and cemented tibial components in young patients with osteoarthritis.

PURPOSE: The aim of this study was to compare the outcomes of tibial fixation with either a cemented or cementless with screw augmentation component in young patients with non-inflammatory arthritis. METHODS: Ninety-three patients aged 55 or younger with non-inflammatory arthritis were randomized to compare outcomes between cemented tibial fixation (48 patients) and cementless fixation with screw augmentation (45 patients). The femoral component was cementless in both groups. Post-operative evaluation was assessed by the clinical and radiological criteria of The Knee Society and WOMAC questionnaire. RESULTS: The median follow-up was 6.7 (5-12) years. Significant differences were found for knee score (p = 0.02), range of motion (p = 0.04), and WOMAC score (p = 0.03). In the cemented group, there was one deep wound infection, four tibial aseptic loosening, and one polyethylene wear, all of which were revised. In the cementless group there was one tibial aseptic loosening and one polyethylene wear, both being revised. There was no difference in revision rate, and the cumulative survival at 9-year for aseptic reason was 93.7 % (95 % CI, 82-100 %) in the cementless group and 90.0 % (95 % CI, 80-100 %) in the cemented group (n.s.). CONCLUSIONS: Cementless total knee arthroplasty was found to be a reliable option in younger patients with osteoarthritis. Although the revision rate and survival were similar in both groups, better clinical outcomes were obtained with cementless tibial components.

Cementless total knee arthroplasty in obese patients: a prospective matched study with follow-up of 5-10 years.

A prospective matched cohort study was performed to compare outcomes of cementless total knee arthroplasties between 171 knees in obese patients (BMI ≥ 30) and 171 non-obese patients (BMI < 30). Mean follow-up was 7 years. There were no significant differences in overall functional outcomes or components alignment. In the obese group, there were 14 perioperative complications, 9 revisions, and 5 other patients were considered clinical failures, whereas in the non-obese group there were 3, 5, and 7, respectively. There were no significant differences between obese class I-II and class III (morbid) subgroups. The obese and non-obese groups had similar implant survivorship at 7 years. Although TKA outcome in obese was satisfactory, these patients should be informed of the perioperative risks, and advised to lose weight prior to surgery.

Periodontally Accelerated Osteogenic Orthodontics (PAOO) technique in cleft patients: A complement to orthognathic surgery in dentoalveolar expansion. A case series report.

The aim of this study was to describe a surgical technique that can be used to solve dentofacial deformities in cleft palate patients with maxillary hypoplasia in order to increase maxillary alveolar bone width, without modifying the skeletal base, and therefore, keeping the velopharyngeal function unaltered. Four patients with a history of cleft palate not associated with syndrome and treated under conventional surgical protocol during their childhood, underwent PAOO surgery incorporating L-PRF, followed by an accelerated orthodontic treatment with checkups every two weeks. All patients reached the desired occlusion without modifying their skeletal bases and velopharyngeal function. Orthodontic treatments were finished between 10 and 14 months after surgery without complications. There were no observed complications in the velopharyngeal postsurgical function and an increase in the arch width was achieved in all cases, along with a reduced orthodontic treatment time. The clinical results obtained confirm that PAOO technique is a safe and reliable complement to orthognathic surgery in the surgical treatment of cleft patients. By increasing the perimeter of the maxillary dentoalveolar ridge, the segmentation of the maxilla could be avoided, increasing the post operatory stability of these patients.

Effects of reader's facial expression on syntactic processing: A brain potential study.

Embodied views of language support that facial sensorimotor information can modulate language comprehension. The aim of this study is to test whether the syntactic processing of simple sentences, as measured with event-related brain potentials (ERP), could be affected by reader's facial expressions. Participants performed a correctness decision task using sentences that could be either correct (50%) or contain a morphosyntactic disagreement (either in gender or number), while making one of four facial expressions: participants either (a) posed no facial expression ("control" condition) (b) brought their eyebrows together, making the ends of two golf tees touch ("frown" condition), (c) held a pencil with their teeth ("smile" condition), or (d) held the pencil using their lips ("non-smile" condition). In all conditions the customary left anterior negativities did not appear. In contrast, an N400-like component emerged, which was larger for the "frown" condition and reduced in the "smile" and "non-smile" conditions. These results can be interpreted as the consequence of either an unconscious emotion induction or an interplay between the motor and the language systems subsequent to the effort needed to hold the facial expression.

Does dynamic information about the speaker's face contribute to semantic speech processing? ERP evidence.

Face-to-face interactions characterize communication in social contexts. These situations are typically multimodal, requiring the integration of linguistic auditory input with facial information from the speaker. In particular, eye gaze and visual speech provide the listener with social and linguistic information, respectively. Despite the importance of this context for an ecological study of language, research on audiovisual integration has mainly focused on the phonological level, leaving aside effects on semantic comprehension. Here we used event-related potentials (ERPs) to investigate the influence of facial dynamic information on semantic processing of connected speech. Participants were presented with either a video or a still picture of the speaker, concomitant to auditory sentences. Along three experiments, we manipulated the presence or absence of the speaker's dynamic facial features (mouth and eyes) and compared the amplitudes of the semantic N400 elicited by unexpected words. Contrary to our predictions, the N400 was not modulated by dynamic facial information; therefore, semantic processing seems to be unaffected by the speaker's gaze and visual speech. Even though, during the processing of expected words, dynamic faces elicited a long-lasting late posterior positivity compared to the static condition. This effect was significantly reduced when the mouth of the speaker was covered. Our findings may indicate an increase of attentional processing to richer communicative contexts. The present findings also demonstrate that in natural communicative face-to-face encounters, perceiving the face of a speaker in motion provides supplementary information that is taken into account by the listener, especially when auditory comprehension is non-demanding.

The 3 R's for Platelet-Rich Fibrin: A "Super" Tri-Dimensional Biomaterial for Contemporary Naturally-Guided Oro-Maxillo-Facial Soft and Hard Tissue Repair, Reconstruction and Regeneration.

Platelet-Rich fibrin (PRF) is a three-dimensional (3-D) autogenous biomaterial obtained via simple and rapid centrifugation from the patient's whole blood samples, without including anti-coagulants, bovine thrombin, additives, or any gelifying agents. At the moment, it is safe to say that in oral and maxillofacial surgery, PRFs (particularly, the pure platelet-rich fibrin or P-PRF and leukocyte and platelet-rich fibrin or L-PRF sub-families) are receiving the most attention, essentially because of their simplicity, cost-effectiveness, and user-friendliness/malleability; they are a fairly new "revolutionary" step in second-generation therapies based on platelet concentration, indeed. Yet, the clinical effectiveness of such surgical adjuvants or regenerative platelet concentrate-based preparations continues to be highly debatable, primarily as a result of preparation protocol variability, limited evidence-based clinical literature, and/or poor understanding of bio-components and clinico-mechanical properties. To provide a practical update on the application of PRFs during oral surgery procedures, this critical review focuses on evidence obtained from human randomized and controlled clinical trials only. The aim is to serve the reader with current information on the clinical potential, limitations, challenges, and prospects of PRFs. Accordingly, reports often associate autologous PRFs with early bone formation and maturation; accelerated soft-tissue healing; and reduced post-surgical edema, pain, and discomfort. An advanced and original tool in regenerative dentistry, PRFs present a strong alternative and presumably cost-effective biomaterial for oro-maxillo-facial tissue (soft and hard) repair and regeneration. Yet, preparation protocols continue to be a source of confusion, thereby requiring revision and standardization. Moreover, to increase the validity, comprehension, and therapeutic potential of the reported findings or observations, a decent analysis of the mechanico-rheological properties, bio-components, and their bioactive function is eagerly needed and awaited; afterwards, the field can progress toward a brand-new era of "super" oro-dental biomaterials and bioscaffolds for use in oral and maxillofacial tissue repair and regeneration, and beyond.

Reboxetine addition in patients with mirtazapine-resistant depression: a case series.

OBJECTIVES: Treatment-resistant depression is a common occurrence in clinical practice as well as combination treatment with 2 different antidepressants. In the present case series, we study the effectiveness of the addition of reboxetine, during 12 weeks, to 14 outpatients diagnosed with major depressive disorder, according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria, who had previously failed to respond or who had only responded partially, over a period of 6 weeks, to conventional treatment with mirtazapine. METHODS: Evaluation of antidepressant efficacy was carried out through the application of the 21-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). RESULTS: The percentages of responders (HDRS>or=50%), patients in remission (HDRS

Use of leukocyte and platelet-rich fibrin (L-PRF) in periodontally accelerated osteogenic orthodontics (PAOO): Clinical effects on edema and pain.

BACKGROUND: Demand for shorter treatment time is common in orthodontic patients. Periodontally Accelerated Osteogenic Orthodontics (PAOO) is a somewhat new surgical procedure which allows faster tooth movement via combining orthodontic forces with corticotomy and grafting of alveolar bone plates. Leukocyte and Platelet-Rich Fibrin (L-PRF) possess hard- and soft-tissue healing properties. Further, evidence of pain-inhibitory and anti-inflammatory potential is growing. Therefore, this study explores the feasibility, intra- and post-operative effects of using L-PRF in PAOO in terms of post-operative pain, inflammation, infection and post-orthodontic stability. MATERIAL AND METHODS: A pilot prospective observational study involving a cohort of 11 patients was carried out. A Wilcko's modified PAOO technique with L-PRF (incorporated into the graft and as covering membrane) was performed with informed consent. Post-surgical pain, inflammation and infection were recorded for 10 days post-operatively, while the overall orthodontic treatment and post-treatment stability were followed up to 2 years. RESULTS: Accelerated wound healing with no signs of infection or adverse reactions was evident. Post-surgical pain was either "mild" (45.5%) or "moderate" (54.5%). Immediate post-surgical inflammation was either "mild" (89.9%) or "moderate" (9.1%). Resolution began on day 4 where most patients experienced either "mild" or no inflammation (72.7% and 9.1%, respectively). Complete resolution was achieved in all patients by day 8. The average orthodontic treatment time was 9.3 months. All cases were deemed stable for 2 years. CONCLUSIONS: L-PRF is simple and safe to use in PAOO. Combination with traditional bone grafts potentially accelerates wound healing and reduces post-surgical pain, inflammation, infection without interfering with tooth movement and/or post-orthodontic stability, over a 2 years period; thus alleviating the need for analgesics and anti-inflammatory medications. KEY WORDS: Periodontally accelerated osteogenic orthodontics, leukocyte and platelet-rich fibrin, corticotomy, osteogenesis, grafts.

Stress induced by the socially evaluated cold-pressor test cause equivalent deficiencies of sensory gating in male subjects with schizophrenia and healthy controls.

It is known that patients with schizophrenia show a deficiency in the prepulse inhibition reflex (PPI). These patients display abnormalities in autonomic nervous system and hypothalamic-pituitary-adrenal function and may have an altered sensitivity to stress. To date, no studies have been carried out to determine the effect of acute stress on the PPI. We investigated whether there was a differential response in reactivity to acute stress caused by the socially evaluated cold-pressor test (SECPT) in a sample of 58 chronic male patients with schizophrenia and 28 healthy control subjects. PPI, salivary cortisol and heart rate (HR) were measured. The patients were evaluated in two sessions (with and without the SECPT) 72 h apart and basal measurements were carried out and 30 min post-startle probe. We found an increase in salivary cortisol levels and the HR with SECPT condition in both groups and a significantly lower PPI% in patients with schizophrenia. The most relevant findings of this study are that the impairment of the PPI is increased by stress. Stress-induced increase in cortisol in both groups, mainly in healthy control group which allows us to hypothesize that at least such deterioration may be due to the hypercortisolemia caused by the SECPT.

Reboxetine adjunct for partial or nonresponders to antidepressant treatment.

BACKGROUND: To investigate the usefulness of the combination therapy with two antidepressants from different pharmacological families in treatment-resistant depressive patients. METHODS: In this prospective 6 weeks open-label study, we assessed the effectiveness of the addition of reboxetine to 61 depressive patients that had previously not responded, or had done so only in a partial way, to conventional treatment, in monotherapy, with selective serotonin reuptake inhibitors (SSRIs), venlafaxine or mirtazapine. Data were analyzed on an intent-to-treat basis, using the last-observation-carried-forward (LOCF) method. RESULTS: Mean decrease on the 21-item Hamilton Depression Rating Scale (HDRS) score was 48.9% and on the Clinical Global Impressions Scale (CGI), 38.9%. At the end of the treatment, 62.3% of the patients were evaluated as improvement (CGI < 4), 54.1% as responders (HDRS < or = 50%) and 45.9% in remission (HDRS < or = 10). No serious side effects were observed during combination therapy, being more frequent increased sweating (8.2%) and dry mouth (6.6%). CONCLUSIONS: These findings suggest that the strategy of combination with reboxetine may be an effective and well-tolerated tool in treatment-resistant patients who have failed to adequately respond to monotherapy with SSRIs, venlafaxine or mirtazapine.

Structure, biodegradation behavior and cytotoxicity of alkali-containing alkaline-earth phosphosilicate glasses.

We report on the effect of sodium on the structure, chemical degradation and bioactivity of glasses in the CaO-MgO-SiO2-P2O5-CaF2 system. The (29)Si and (31)P magic angle spinning-nuclear magnetic resonance spectroscopy of melt-quenched glasses with varying Na2O/MgO ratios exhibit a silicate glass network with the dominance of Q(2)(Si) units and phosphorus mainly forming orthophosphate species. Sodium incorporation in the glasses did not induce a significant structural change in the silicate network, while it did influence the phosphate environment due to its lower ionic field strength in comparison with that of magnesium. The apatite forming ability of glasses has been investigated by immersion of glass powders in simulated body fluid (SBF) for time durations varying between 1h and 7 days while their chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. Increasing Na(+)/Mg(2+) ratio caused a decrease in the chemical durability of glasses and in the apatite forming ability especially during initial steps of interaction between glass and SBF solution. The cellular responses were observed in vitro on bulk glass samples using mouse-derived pre-osteoblastic MC3T3-E1 cell line. The preliminary study suggested that the increasing alkali-concentration in glasses led to cytotoxicity in the cell culture medium.

Conducting polymer nanowire-based chemiresistive biosensor for the detection of bacterial spores.

Polypyrrole nanowires (Ppy) were assembled onto microfabricated gold interdigitated microelectrodes, to construct a chemiresistive biosensor for the detection of Bacillus globigii, used as simulant of the threatening bioterrorism agent B. anthracis. The fabricated biosensor showed good linear correlation (r(2)=0.992) for low spore concentrations ranging from 1 to 100 CFU (colony forming units)/mL, a concentration that could be used in a bioterrorism attack, with a response time of 30 min, after which the sensor was saturated. The performance of the biosensor was also assessed in the absence of anti-B. globigii antibodies and in the presence of non-target bacterial cells (Escherichia coli) showing no significant non-specific interactions. We believe that Ppy nanowires are a good platform for the detection and also quantification of large molecules and biocomponents even at low concentrations.

Psychopathology in the Lujan-Fryns syndrome: report of two patients and review.

We report on two new patients, the propositus and his maternal uncle, with Lujan-Fryns syndrome (LFS). One presented with mild mental retardation and both patient had Marfanoid habitus and similar craniofacial anomalies (they had a long and narrow face, small mandible, high-arched palate, and hypernasal voice) as previously reported by Lujan et al. in 1984 and Fryns and Buttiens in 1987. One of our patients had agenesis of the corpus callosum as described by Lujan. The second patient had an ascending aortic aneurysm like the patient described by Wittine et al. 1999. Both patients showed similar behavior and psychiatric disorders. In addition, we reviewed the literature for the presence of psychopathology in LFS. After studying the 32 published cases and the 2 described in this article, we found that more than 90% of the patients present with some type of psychopathology, the most frequent being an autistic-like disorder. In our opinion, the agenesis of the corpus callosum (complete or partial) and ascending aorta aneurysm are manifestations of LFS, and thus brain MRI and echocardiogram should be part of the routine evaluation. Additionally, the high prevalence of psychopathological alterations in these patients suggests the need for psychiatric evaluation at the time of diagnosis.