Effects of plasma transfusions on antithrombin levels after paediatric liver transplantation.

BACKGROUND AND OBJECTIVES: Thrombotic complications affect 3-10% of patients after liver transplantation (LT), leading to potentially life-threatening complications. In the days following LT, antithrombin (AT) is decreased longer than pro-coagulant factors, thus favouring a pro-thrombotic profile. Plasma transfusions are given empirically in some centres to correct AT levels following LT. We assessed the effect of plasma transfusion on AT levels after paediatric LT. MATERIALS AND METHODS: Prospective single-centre observational study in 20 consecutive paediatric LT recipients over a 24-month period. Plasma was administered twice daily (10 ml/kg/dose) according to an existing protocol. AT levels were measured once daily, immediately prior to and one hour after the morning plasma transfusion. Sample size was calculated based on a non-inferiority hypothesis. RESULTS: The median age and weight were 11.6 years (IQR 2.8; 14.7) and 40 kg (IQR 12.75; 44.8), respectively. We collected 85-paired blood samples. The median AT level prior to plasma transfusion was 58%. The median difference in AT levels before and after plasma transfusion was 4.2% (P = 0.001). Changes in AT levels after plasma transfusion were not correlated with baseline AT levels (R = 0.19) or patient weight (R = 0.18). CONCLUSION: Plasma transfusions only marginally increase AT levels in children after LT. Therefore, prophylactic plasma transfusions probably do not seem to confer an advantage in the routine management of paediatric LT patients. Randomized controlled trials are needed to identify the optimal anticoagulation strategy in this specific population.

SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.

Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome.

Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

INTRODUCTION: Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. AIM: Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. METHODS: Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard. RESULTS: When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. CONCLUSION: In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard.

[New oral anticoagulants: from theory to practice]. / Hémostase. Nouveaux anticoagulants oraux: de la théorie à la pratique.

Physicians are confronted with many new antithrombotic drugs, either antiplatelet agents or new oral anticoagulants (NOAC). Targets of NOAC are specific (either anti-IIa or antiXa) and clinical studies have shown that NOAC are as efficacious and as safe as "old" anticoagulants (heparin, low molecular weight heparin, vitamin K antagonists); moreover they present some advantages. Indeed, NOAC have a wide therapeutic window and do not require laboratory monitoring. Therefore, it is very tempting to prescribe them on a large scale basis in patients at risk or having thromboembolic diseases. However, things are not so simple in the day-to-day practice and this review aims at answering in a brief and simplified manner to some questions.

[Perioperative management of new antiplatelet drugs]. / Gestion péri-interventionnelle des nouveaux agents antiplaquettaires.

The management of antiplatelet drugs in the perioperative setting is based on an individual evaluation of the thrombotic and bleeding risks. When the bleeding risk is deemed low, continuation of the dual antiplatelet therapy is usually recommended, especially in high thrombotic risk settings. When the bleeding risk is deemed moderate, at least one antiplatelet agent should be continued, usually aspirin, and clopidogrel and ticagrelor should be discontinued 5 days and prasugrel 7 days before surgery. In some rare instances of high bleeding risk, discontinuation of aspirin 3 days before surgery is usually acceptable. In high thrombotic settings, bridging with an intravenous antiplatelet drug with a short half-life may be considered.

Combined effects of whole-body vibration, resistance exercise, and vascular occlusion on skeletal muscle and performance.

The purpose of this study was to evaluate the effects of a new high-intensity training modality comprised of vibration exercise with superimposed resistance exercise and vascular occlusion (vibroX) on skeletal muscle and performance. Young untrained women were randomized to either train in a progressive mode on 3 days per week for 5 weeks ( N=12) or to maintain a sedentary lifestyle ( N=9). VibroX increased peak cycling power (+9%, P=0.001), endurance capacity (+57%, P=0.002), ventilatory threshold (+12%, P<0.001), and end-test torque (+15%, P=0.002) relative to the sedentary group. Training load increased by 84.5% ( P<0.001) after vibroX. The increases were paralleled by increases in myosin heavy chain type 1 vastus lateralis muscle fiber cross-sectional area (+14%, P=0.031) and proportion (+17%, P=0.015), thigh lean mass (+4%, P=0.001), capillary-to-fiber ratio (+14%, P=0.003), and cytochrome c oxidase activity. Conversely, maximal values for oxygen consumption, cardiac output, isokinetic leg extension power and jumping power remained unaffected. Notably, vastus lateralis muscle adaptations were achieved with a very low weekly training volume. We conclude that vibroX quickly increases muscle (fiber) size, capillarization, and oxidative potential, and markedly augments endurance capacity in young women.

Do miRNAs Have a Role in Platelet Function Regulation?

MicroRNAs (miRNAs) are a class of non-coding RNAs known to repress mRNA translation and subsequent protein production. miRNAs are predicted to modulate many targets and are involved in regulating various cellular processes. Identifying their role in cell function regulation may allow circulating miRNAs to be used as diagnostic or prognostic markers of various diseases. Increasing numbers of clinical studies have shown associations between circulating miRNA levels and platelet reactivity or the recurrence of cardiovascular events. However, these studies differed regarding population selection, sample types used, miRNA quantification procedures, and platelet function assays. Furthermore, they often lacked functional validation of the miRNA identified in such studies. The latter step is essential to identifying causal relationships and understanding if and how miRNAs regulate platelet function. This review describes recent advances in translational research dedicated to identifying miRNAs' roles in platelet function regulation.

Post-Space Treatment Influences the Bond Strength In Endodontically Treated Teeth: A Systematic Review and Meta-Analysis of In Vitro Studies.

OBJECTIVES: This systematic review of in vitro studies investigated the influence of the post-space treatment used to remove the smear layer on the bond strength of the post to root canal dentin. METHODS AND MATERIALS: In vitro studies included in this study were identified from PubMed/MEDLINE, Lilacs, and Scopus databases up until March 2019, without limits on publication year or language. Two reviewers independently selected the studies based on the inclusion and exclusion criteria, extracted the data, and evaluated the risk of bias of all studies. A random effects model was used for pairwise meta-analyses (control vs. post-space preparation groups) at a significance level of p<0.05. RESULTS: Of the 2,832 potentially eligible studies, 453 studies were selected for full-text analysis, and 75 were included in this systematic review. Only one study was considered to have a low risk of bias. Overall, post-space treatment significantly improves the bond strength to root canal dentin (p<0.00001). CONCLUSION: Post-space treatment has a positive influence on the bond strength of the post to root canal dentin. In this review, the post-space treatments that improve the adhesive resistance of the post were ethanol, sodium hypochlorite, and ethylene diamine tetra-acetic acid (NaOCl + EDTA), NaOCl + EDTA + ultrasound, erbium-doped yttrium aluminium garnet laser (Er:YAG laser), neodymium-doped yttrium aluminium garnet laser (Nd:YAG laser), and diode laser.

Oral implications of the vegan diet: observational study.

AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.

Cone beam computed tomography role in diagnosis and treatment of impacted canine patient's: a case report.

A tooth is impacted when its apex is formed but does not erupt as expected during the physiological timeframe of eruption. The frequency with which the upper canine is impacted in the sample examined varies from 1% to 5% of the population in the second decade of life. The most frequent causes of inclusion of the upper canine are: lack of resorption or precocious loss of the root of the deciduous, agenesis of the lateral, an anomaly in its shape, lack of space in the arch, presence of a mechanical obstacle to the eruption, and lastly due to hereditary factors. When dental impaction is suspected, radiographic examination is indicated to evaluate the effect that the impacted element is having in the context of the osseous structure and to evaluate its relationships with adjacent teeth, the presence of mechanical obstacles, the placement of the inclusion and its orientation in space, how well developed the root is, and any anomalies in its shape. In addition to the classic orthopantomography (OPT), endoral radiography, teleradiography, can be used in order to obtain three-dimensional and life-size images, techniques of computed tomography (CT). In particular, cone beam CT, obtains this type of image using a radioactive dose comparable to that obtained summarizing the classic radiographic examinations requested by an orthodontist and moreover less that that administered when using classic multi-layer spiral CT medical equipment. This case report describes the diagnostic iter and orthodontic-surgical treatment of a patient with enclosure of the right upper canine.

[Update on new antithrombotic treatments]. / Hémostase. Le point sur tes nouveaux antithrombotiques.

Update on new antithrombotic treatments Antithrombotic treatments are frequently prescribed in different clinical situations. Classical anticoagulants have some disadvantages. New anticoagulants have emerged recently. Fondaparinux is now prescribed for both prophylaxis and treatment of venous thromboembolism. Two drugs are particularly interesting: rivaroxaban and dabigatran. Concerning the new antiplatelet agents, many molecules such as prasugrel, ticagrelor, cangrelor, SCH530348 or terutroban have appeared recently. They are directed either to the P2Y12 receptor or to other original targets. Studies have shown an increased bleeding risk for some of them as well as unexpected side effects. In the next future, these new molecules could allow a more individualised prescription of antithrombotic agents.

Effect of Different Surface Treatments of Resin Relined Fiber Posts Cemented With Self-adhesive Resin Cement on Push-out and Microtensile Bond Strength Tests.

CLINICAL RELEVANCE: When luting relined fiber posts with self-adhesive cement, the surface treatment of the posts influences the adhesion of the fiber posts to root dentin. SUMMARY: This study evaluated the effect of surface treatment and silanization of resin composite on the bond strength of relined fiber posts cemented with self-adhesive resin cement. Push-out and microtensile bond strength (MTBS) tests were performed in this study. The endodontic treatment of 80 single-rooted bovine teeth was first performed in the push- out test segment, followed by weakening the intracanal walls by diamond bur. Then, the glass fiber posts were adapted with resin composite to fill the root canals, followed by photoactivation and resin surface conditioning according to four different experimental conditions: no conditioning as control, 10% hydrofluoric acid, 35% hydrogen peroxide, or air abrasion with alumina particle (all groups were subdivided into "with silanization" or "without silanization," thus totaling eight experimental groups). Self-adhesive resin cement was used for the post cementation. Four slices per tooth were obtained for the push-out tests. Next, 160 blocks of resin composite were first produced for the MTBS tests; their bonding surfaces were conditioned (as mentioned, ie, eight treatments), and they were cemented to each other. The 80 sets (n=10/treatment) were then cut into microbars (16/set): eight were immediately tested, while the other eight were thermocycled (12,000×) and stored (120 days) before MTBS. Failure modes and topographic analyses were performed after treatments. There was no statistically significant difference for the push-out results. In MTBS, surface treatment and silanization had a significant effect (p<0.001). Aging decreased bond strength for all groups. Considering the aged groups, air abrasion promoted the highest values and silanization improved bond strength for all treatments except air abrasion. The alumina particle air abrasion of the relining resin composite promoted the highest bond strengths when luting with self-adhesive resin cement.

Reliability of measurements with Innocor during exercise.

Cardiac output represents the primary determinant of cardiovascular function. Therefore, understanding how cardiac output is regulated during exercise is crucial. A recently developed tool for determining cardiac output is the Innocor rebreathing system, which also incorporates an ergospirometry unit. So far, Innocor's test-retest reliability under exercise conditions has not been determined in healthy participants. Therefore, 15 male and 15 female healthy participants [30.6 y (SD 4.5); 68.0 kg (SD 10.5)] performed 2 test sessions, each consisting of 2 graded exercise tests to volitional exhaustion. We determined intra- and inter-session reliability of cardiac output, oxygen consumption, carbon dioxide output, and ventilation at 130 W and at peak exercise. For cardiac output, we found averaged coefficients of variation ranging from 4.3 (intra-session, 130 W) to 10.0% (inter-session, rest). For oxygen consumption, coefficients of variation ranged from 3.4 (intra-session, peak) to 5.7% (inter-session, peak). Coefficients of variation for carbon dioxide output were between 4.4 (intra-session, peak) and 6.6% (inter-session, peak), and for ventilation between 5.1 (intra-session, 130 W) and 7.0% (intra-session, peak). Innocor delivers safe and reliable measurements of cardiac output, gas exchange, and ventilation. Therefore, Innocor can be used to assess these parameters in exercise physiology studies as well as in performance diagnostics.

Effect of Ferrule Thickness on Fracture Resistance of Teeth Restored With a Glass Fiber Post or Cast Post.

PURPOSE: To investigate the influence of ferrule thickness on fracture resistance after mechanical cycling of teeth restored with different intracanal posts. METHODS AND MATERIALS: One hundred twenty bovine incisor teeth were randomized into six study groups, based on the intracanal post used (fiber post or cast post and core) and the presence and thickness of a ferrule (without ferrule, presence of 0.5-mm or 1-mm-thick ferrule, retaining unaltered 2-mm ferrule height). The root posts and the metal crowns were cemented using an adhesive cement. The samples were subjected to mechanical cycling (at 37°C, 45°, 130 N, 2.2 Hz, and 2 × 106 pulses). Afterward, they were subjected to a fracture load test at a speed of 0.5 mm/min and on a 45° slope until failure occurred. The failures were classified as favorable or unfavorable. The fracture resistance data were analyzed with two-way analysis of variance and Tukey test. The chi-square test was used to analyze the pattern of failure. RESULTS: When considering the cast post and core, the 1-mm ferrule thickness group presented a higher resistance to fracture than did the group in which a ferrule was not used (p=0.001). When using a glass fiber post, the groups showed no differences in fracture resistance. Overall, 96.7% of the specimens survived the mechanical cycling. Of the fractures, 58.6% of the fractures were unfavorable, while 41.6% were favorable. CONCLUSIONS: A thicker ferrule statistically increased the fracture resistance only for cast post and core when it was at least 1 mm thick, despite causing more unfavorable failures. Thus, ferrule thickness should be considered when choosing different intracanal posts, to reduce the occurrence of unfavorable failures. In the absence of a ferrule, the use of a cast post and core presents more favorable failures, and in the presence of a 1-mm-thick ferrule, the use of a glass fiber post seems to be the best clinical decision.

Management of antiplatelet therapy for non elective invasive procedures of bleeding complications: proposals from the French working group on perioperative haemostasis (GIHP), in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR).

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.

Biological properties of Cakile maritima Scop. (Brassicaceae) extracts.

OBJECTIVE: Cakile maritima scop. (CKM) is a herbaceous plant (Brassicaceae) growing also in high salinity environment. It is an annual plant growing in clumps or mounds in the sand on beaches and bluffs. MATERIALS AND METHODS: Stems, seeds, leaves and flowers of CKM were used to obtain 70% of ethanol extracts. The phenolic content of the different extracts was evaluated by the Folin-Ciocalteu method. The separation of phytochemical compounds was based on ultra-performance liquid chromatography coupled to mass spectrometry. Radical scavenging activity was determined by 1,1-diphenyl-2-picrylhydrazyl assay. The qualitative assay for the inhibition of α-glucosidase was quantified spectrophotometrically and the anti-inflammatory activity was determined in the U937 cell line by using gene expression of pro-inflammatory cytokines. Cell viability assay was done in U937, MM1S, and U266 cells by using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The antimicrobial activity was investigated by MIC determination, "double-triple combinations assay", and growth inhibition curves analysis, using the extracts individually or in various combination. Statistical analysis was performed by the Student's t-test and ANOVA. RESULTS: All parts of the plant exhibited a high antioxidant capacity as measured by DPPH assay. Furthermore, all extracts reduced (about 10 folds) the expression of inflammatory cytokines in macrophage following LPS treatment. As regards the antibacterial activity, only the seeds extract was able to inhibit both Gram-negative and Gram-positive bacteria when tested alone, whereas dual combinations of different extracts (leaves, flowers, stems and seeds) caused bacterial inhibition exhibiting a synergic action. Finally, we showed that the extracts did not exhibit cytotoxic effects in normal cells and that, surprisingly, it exhibited an anti-proliferative effect (inhibition ≈80%) in multiple myeloma U266 cells. CONCLUSIONS: Our study suggests that CKM possesses antioxidant, anti-inflammatory, antibacterial, anti-proliferative activities and such pleiotropic effects may be exploited under various pathological conditions.

HER-2/neu overexpression and amplification in uterine serous papillary carcinoma: comparative analysis of immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization.

Uterine serous papillary carcinoma (USPC) is a rare and highly malignant form of endometrial cancer (EC) characterized by early metastasis, chemoresistance, and high mortality rate. Little is known about USPC tumorigenesis even if recently a HER-2/neu role has been suggested in its development and progression. The aim of the present study was to evaluate HER-2 expression by immunohistochemistry (IHC) in 12 USPC formalin-fixed, paraffin-embedded (FFPE) samples. Moreover, we looked at the correlation between HER-2 protein expression and HER-2/neu gene amplification by fluorescence in situ hybridization (FISH), other than HER-2/neu messenger RNA expression by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Finally, these results have been compared with commonly evaluated clinical features in EC patients, in order to define the potential prognostic value of HER-2/neu overexpression in USPCs. A high expression of HER-2 protein by IHC was noted in 2 of 12 patients (16.6%), and the same cases showed specific HER-2/neu gene amplification by FISH. All the samples investigated displayed a perfect concordance between IHC and FISH data. Five (41.6%) of 12 tumors demonstrated polysomy of chromosome 17 and, focusing on the 2 USPCs that showed HER-2/neu overexpression, one of them (50%) was polysomic for chromosome 17. All the other USPC cases (58.4%) showed to be disomic for chromosome 17. Quantitative RT real-time PCR performed on complementary DNA obtained from all FFPE USPC samples showed a complete correlation with FISH and IHC data. Moreover, HER-2/neu overexpression was associated with a poorer overall survival and a very low relapse-free survival time, thus being considered a candidate marker of worse overall prognosis in USPC. The use of trastuzumab (Herceptin), a monoclonal antibody directed against HER-2/neu, for the therapy of patients with HER-2/neu-positive USPCs should be further investigated in clinical trials.

Paneth cells: histochemical and morphometric study in control and Solanum glaucophyllum intoxicated rabbits.

The intestinal epithelium has a critical roll in host defence. One specialised cell type involved in this function is the Paneth cell, which secretes many substances with antimicrobial properties in response to different stimuli. Under pathological conditions, changes in the Paneth cell number, morphology and location as well as in granule number, morphology and composition have been reported. In the normal animal, 1,25-dihydroxyvitamin D3 participates in the maintenance of mineral homeostasis, immunomodulation and cell proliferation and differentiation. Solanum glaucophyllum, a calcinogenic plant containing high levels of 1,25-dihydroxyvitamin D3, is responsible for a condition known as enzootic calcinosis in ruminants, characterised by loss of body condition and mineralization of soft tissues. Using and established rabbit model, this study analyses the changes that rabbit Paneth cells undergo during intoxication with S. glaucophyllum. Male New Zealand white rabbits were experimentally intoxicated with S. glaucophyllum for 15 or 30 days. Lectin, immunohistochemical and morphometric studies were carried out on Paneth cells from samples of jejunum. SBA, DBA and WGA lectins bound to Paneth cells-granules in both normal and intoxicated rabbits, with more heterogenity in the labelling of granules from intoxicated rabbits. Paneth cells in both groups were immunonegative for lysosyme. A time and dose-dependent increase in the size and number of Paneth cells was found in both intoxicated groups. We suggest that the changes described in these cells may be directly or indirectly induced by S. glaucophyllum intoxication.

Impending paradoxical embolism. When and how to treat?

Impending paradoxical embolism (IPDE) is the presence of an entrapped thrombus through the patent foramen ovale (PFO). Usually IPDE are diagnosed by echocardiography or thoracic CT-scan performed during the evaluation of patient presenting with a suspicion of pulmonary embolism (PE). We report the case of a 73-year-old patient presenting with a very large IPDE successfully treated with cardiac surgery and we focus our discussion on the treatment modalities of this rare entity (anticoagulation alone, fibrinolytic regimens, cardiac surgery, percutaneous thrombectomy) and on PFO management after IPDE.