Stage based recipient and donor outcome in twin-to-twin transfusion syndrome treated by fetoscopic laser surgery using Solomon technique.

OBJECTIVE: To evaluate twin survival stratified by Quintero stage in patients with twin-to-twin transfusion syndrome (TTTS) after Solomon laser treatment. METHODS: Single center cohort of consecutive twin pregnancies treated with Solomon laser for TTTS. Preoperative Quintero stage, perioperative characteristics and obstetric factors were related to neonatal survival of the recipient and donor at discharge. Determinants of twin survival were evaluated using univariate, logistic regression and cumulative survival probability analyses. RESULTS: Of 402 twins with TTTS, 80 (19.9%) had stage I, 126 (31.3%) stage II, 169 (42%) stage III and 27 (6.7%) stage IV. Post laser TAPS or recurrent TTTS occurred in 19 (4.7%) patients and 11 (2.7%) required repeat laser. Preterm premature rupture of membranes occurred in 150 (37.3%) patients and median gestational age of delivery 32+1 weeks. In 303 (75.4%) both twins were alive at discharge; [66 (82.5%) in stage I, 101 (80.2%) in stage II, 114 (67.5%) in stage III and 22 (81.5%) in stage IV, p=0.062]. Compared to recipients, donor survival was only lower in stage III (155 (91.7%) recipients vs 118 (69.8%) donors, Chi square 24.685, p<0.0001). Larger intertwin size discordance and umbilical artery (UA) end-diastolic velocity (EDV) determined donor demise (Nagelkerke R2 0.38, P<0.001). Overall, spontaneous post laser donor demise accounted for the majority (39.5%) of all losses. Cumulative donor survival decreased from 92% to 65% with size discordance >30% and 48% when UA EDV was absent (p<0.001). CONCLUSION: Solomon laser achieves TTTS resolution and double survival in a high proportion of cases. Recipient and donor survival is comparable unless there is significant size discordance and placental dysfunction. This degree of unequal placental sharing, typically found in stage III, is the primary factor preventing double survival due to a higher rate of donor demise. This article is protected by copyright. All rights reserved.

Epidemiology of maxillofacial trauma in the elderly: A European multicenter study.

INTRODUCTION: The progressive aging of European population seems to determine a change in the epidemiology, incidence and etiology of maxillofacial fractures with an increase in the frequency of old patients sustaining craniofacial trauma. The objective of the present study was to assess the demographic variables, causes, and patterns of facial fractures in elderly population (with 70 years or more). MATERIALS AND METHODS: The data from all geriatric patients (70 years or more) with facial fractures between January 1, 2013, and December 31, 2017, were collected. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, etiology, site of facial fractures, synchronous body injuries, Facial Injury Severity Score (FISS). RESULTS: A total of 1334 patients (599 male and 735 female patients) were included in the study. Mean age was 79.3 years, and 66% of patients reported one or more comorbidities. The most frequent cause of injury was fall and zygomatic fractures were the most frequently observed injuries. Falls were associated with a low FISS value (P<.005). Concomitant injuries were observed in 27.3% of patients. Falls were associated with the absence of concomitant injuries. The ninth decade (P<.05) and a high FISS score (P<.005) were associated with concomitant body injuries too. CONCLUSIONS: This study confirms the role of falls in the epidemiology of facial trauma in the elderly, but also highlights the frequency of involvement of females, and the high frequency of zygomatic fractures.

Management of mandibular condylar fractures in patients with atrophic edentulous mandibles.

INTRODUCTION: Treatment of condylar fractures in patients with atrophic edentulous mandibles is a peculiar field that has been little considered in the literature. The aim of the study was to assess the demographic and clinical variables as well as management and outcome of mandibular condylar fractures in edentulous patients with atrophic mandibles that were treated at several European departments of oral and maxillofacial surgery. METHODS: The data of all patients with fractures of the atrophic edentulous mandible from the involved maxillofacial surgical units across Europe between January 1, 2008, and December 31, 2017. Only patients that were diagnosed with condylar fractures of the edentulous atrophic mandible were included. RESULTS: A total of 52 patients met the inclusion criteria and were included in the study: 79% of patients reported one or more comorbidities. Thirty-four unilateral neck or subcondylar fractures, 9 bilateral neck or subcondylar condylar fractures, 7 unilateral head condylar fractures, and 2 bilateral head condylar fractures were diagnosed. No treatment was performed in 37 cases, whereas in 4 patients a closed treatment was decided, and 11 patients underwent open reduction and internal fixation. Outcome was considered to be satisfying in 48 patients, with no complications. CONCLUSIONS: The golden rule still remains that the diagnosis of a subcondylar or neck fracture in an edentulous patient should constitute an indication for open reduction and internal fixation. However, an appropriate choice of management options has to be individualized on a case by case basis, also depending on the patient consent.

Serendipity and the discovery of novel compounds that restore mitochondrial plasticity.

The mitochondrial electron transport chain (ETC) plays a central role in energy generation in the cell. Mitochondrial dysfunctions diminish adenosine triphosphate (ATP) production and result in insufficient energy to maintain cell function. As energy output declines, the most energetic tissues are preferentially affected. To satisfy cellular energy demands, the mitochondrial ETC needs to be able to elevate its capacity to produce ATP at times of increased metabolic demand or decreased fuel supply. This mitochondrial plasticity is reduced in many age-associated diseases. In this review, we describe the serendipitous discovery of a novel class of compounds that selectively target cardiolipin on the inner mitochondrial membrane to optimize efficiency of the ETC and thereby restore cellular bioenergetics in aging and diverse disease models, without any effect on the normal healthy organism. The first of these compounds, SS-31, is currently in multiple clinical trials.

Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis.

BACKGROUND AND PURPOSE: Cardiolipin plays an important role in mitochondrial respiration and cardiolipin peroxidation is associated with age-related diseases. Hydrophobic interactions between cytochrome c and cardiolipin converts cytochrome c from an electron carrier to a peroxidase. In addition to cardiolipin peroxidation, this impedes electron flux and inhibits mitochondrial ATP synthesis. SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2 ) selectively binds to cardiolipin and inhibits cytochrome c peroxidase activity. Here, we examined whether SS-31 also protected the electron carrier function of cytochrome c. EXPERIMENTAL APPROACH: Interactions of SS-31 with cardiolipin were studied using liposomes and bicelles containing phosphatidylcholine alone or with cardiolipin. Structural interactions were assessed by fluorescence spectroscopy, turbidity and nuclear magnetic resonance. Effects of cardiolipin on electron transfer kinetics of cytochrome c were determined by cytochrome c reduction in vitro and oxygen consumption using mitoplasts, frozen and fresh mitochondria. KEY RESULTS: SS-31 interacted only with liposomes and bicelles containing cardiolipin in about 1:1 ratio. NMR studies demonstrated that the aromatic residues of SS-31 penetrated deep into cardiolipin-containing bilayers. SS-31 restored cytochrome c reduction and mitochondrial oxygen consumption in the presence of added cardiolipin. In fresh mitochondria, SS-31 increased state 3 respiration and efficiency of ATP synthesis. CONCLUSIONS AND IMPLICATIONS: SS-31 selectively targeted cardiolipin and modulated its interaction with cytochrome c. SS-31 inhibited the cytochrome c/cardiolipin complex peroxidase activity while protecting its ability to serve as an electron carrier, thus optimizing mitochondrial electron transport and ATP synthesis. This novel class of cardiolipin therapeutics has the potential to restore mitochondrial bioenergetics for treatment of numerous age-related diseases.

Cost-effective application of thermal protection on LPG road transport tanks for risk reduction due to hot BLEVE incidents.

A simplified risk and cost-benefit analysis is presented for the application of thermal protection (TP) on propane and LPG highway tanker trucks operating in North America. A risk analysis is performed to determine the benefits of risk reduction by TP, relative to the costs of applying and maintaining TP on a tanker truck. The results show that TP is cost effective if the tanker truck spends enough time (or travels enough distance) in areas of moderate or high population density. The analysis is very sensitive to a number of inputs, including: (i) value of life, (ii) hot boiling liquid expanding vapor explosion frequency, (iii) public exposure to severe hazards, and (iv) life cost of TP. With this simplified analysis, it is possible to generate tanker truck exposure times to the public that justify the application of TP based on cost and benefit considerations.

Days with severe symptoms: an additional efficacy endpoint in immunotherapy trials.

BACKGROUND: In immunotherapy trials, primary and secondary endpoints often focus on average symptom and medication scores during the pollen season or on days with low symptoms and low medication use. Thus, there is a need for endpoints describing the treatment effect on the most troublesome days in the pollen season. AIMS OF THE STUDY: A possible additional efficacy endpoint, days with severe symptoms during the pollen season, was investigated using data from a multicentre, double-blind, randomized, placebo-controlled trial of the SQ-standardized grass allergy immunotherapy tablet (AIT) (Grazax, Phleum pratense, 75,000 SQ-T/2,800 BAU, ALK, Hørsholm, Denmark). METHODS: The trial included 634 subjects (N(Grass AIT) = 316; N(Placebo) = 318) with grass pollen-induced rhinoconjunctivitis. Six different definitions of a day with severe symptoms were suggested. The number of days with severe symptoms was analysed and odds ratios were calculated. RESULTS: The number and percentage of days with severe symptoms differed between definitions, but overall the analysis of days with severe symptoms showed consistent results (odds ratios: 2.0-3.4) for the different definitions. All definitions showed a reduced risk of having days with severe symptoms in the grass AIT group when compared to the placebo group. CONCLUSIONS: Days with severe symptoms during the pollen season is a relevant additional efficacy endpoint, which can be used in immunotherapy trials to support the clinical interpretation of commonly used efficacy endpoints.

Advances of air pollution science: from forest decline to multiple-stress effects on forest ecosystem services.

Over the past 20 years, the focus of forest science on air pollution has moved from forest decline to a holistic framework of forest health, and from the effects on forest production to the ecosystem services provided by forest ecosystems. Hence, future research should focus on the interacting factorial impacts and resulting antagonistic and synergistic responses of forest trees and ecosystems. The synergistic effects of air pollution and climatic changes, in particular elevated ozone, altered nitrogen, carbon and water availability, must be key issues for research. Present evidence suggests air pollution will become increasingly harmful to forests under climate change, which requires integration amongst various stressors (abiotic and biotic factors, including competition, parasites and fire), effects on forest services (production, biodiversity protection, soil protection, sustained water balance, socio-economical relevance) and assessment approaches (research, monitoring, modeling) to be fostered.

Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy increases clinical efficacy.

BACKGROUND: Sublingual immunotherapy treatment with grass allergen tablets (Grazax) is initiated preseasonally without up-dosing and treatment is continued throughout the entire grass pollen season. AIMS OF THE STUDY: The influence of the duration of preseasonal treatment on clinical efficacy obtained within the grass pollen season was investigated. METHODS: Data from three randomized, double-blind, placebo-controlled, multi-centre trials with varying preseasonal treatment periods were analysed. In the grass pollen season, symptom and medication score reductions relative to placebo were calculated and correlated with the duration of the preseasonal treatment period. RESULTS: The analysis was based on data from 934 patients. A significant reduction in seasonal daily rhinoconjunctivitis symptom and medication scores (17%, CI: 1-33% and 23%, CI: 1-47%, P < 0.05) was observed for patients treated with Grazax compared with placebo after approximately 8 weeks of pretreatment. The magnitude of the reductions in rhinoconjunctivitis symptom and medication scores increased with longer duration of preseasonal treatment (P < 0.0001). CONCLUSIONS: Sublingual immunotherapy with Grazax) must be initiated at least 8 weeks prior to the grass pollen season to provide a significant clinical efficacy. A longer preseasonal treatment period (>8 weeks) improves the clinical efficacy (relative to placebo) during the grass pollen season.

Dynorphin stimulates corticotropin release from mouse anterior pituitary AtT-20 cells through nonopioid mechanisms.

Dynorphin (Dyn) peptides were previously shown to increase plasma corticotropin (ACTH) in the ovine fetus, but the site of its action remains unclear. In the present study, Dyn A(1-17) was found to stimulate ACTH release from mouse anterior pituitary tumor AtT-20 cells in a dose-dependent manner. Naloxone did not block the effect of Dyn A(1-17) and the selective kappa-opioid receptor agonist U50488H did not stimulate ACTH release. Dyn A(2-17), a degradative peptide fragment that does not bind to opioid receptors, also stimulated ACTH release from AtT-20 cells. Although the nonopioid effects of Dyn have previously been attributed to N-methyl-D-aspartate (NMDA) receptors, the ACTH-releasing effects of Dyn A(1-17) in AtT-20 cells were not affected by co-administration of NMDA receptor antagonist LY235959. The ACTH response to Dyn A(1-17) could not be blocked by alpha-helical CRH (CRH antagonist) and was additive with a maximal stimulatory dose of CRH, suggesting different mechanisms of action. These results show that the release of ACTH by Dyn A(1-17) in AtT-20 cells is not mediated by kappa-opioid receptors or by the NMDA receptor.

Heme-solvent coupling: a Mössbauer study of myoglobin in sucrose.

The Mössbauer effect of 57Fe-enriched samples was used to investigate the coupling of 80% sucrose/water, a protein-stabilizing solvent, to vibrational and diffusive modes of the heme iron of CO-myoglobin. For comparison we also determined the Mössbauer spectra of K4 57Fe (CN)6 (potassium ferrocyanide, PFC), where the iron is fully exposed in the same solvent. The temperature dependence of the Mössbauer parameters derived for the two samples proved to be remarkably similar, indicative of a strong coupling of the main heme displacements to the viscoelastic relaxation of the solvent. We show that CO escape out of the heme pocket couples to the same type of fluctuations, whereas intramolecular bond formation involves solvent-decoupled heme deformation modes that are less prominent in the Mössbauer spectrum. With respect to other solvents, however, sucrose shows a reduced viscosity effect on heme displacements and the kinetics of ligand binding due to preferential hydration of the protein. This result confirms thermodynamic predictions of the stabilizing action of sucrose by a dynamic method.

Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVES: The efficacy of a buckwheat herb tea was determined in patients with chronic venous insufficiency (CVI) in a single-centre, randomised, double-blind, placebo-controlled clinical trial. METHODS: Sixty-seven male and female patients (22-74 years) with CVI were randomly divided into two groups after a 2-week run-in period. They received either buckwheat herb tea (Fagopyrum esculentum) or a placebo tea for a period of 3 months. The main outcome measure was the lower leg volume determined by ultrasound. Subjective symptoms were assessed by a clinical symptom score system. The femoral vein diameters were measured by B-scan sonography. In a subgroup of patients capillary permeability was determined by cutaneous fluorescence angiography. RESULTS: Although the mean partial leg volume did not change in the treatment group (from 2041 to 2073 ml), it increased in the placebo group by 110 ml (from 1972 to 2082 ml) according to intent to treat. The difference between the groups was significant. The subjective clinical symptoms were significantly reduced in both groups. The mean diameters of the femoral veins were reduced and capillary permeability was improved, but neither change was statistically significant. No drug-related adverse effects were observed. CONCLUSION: CVI is a very placebo-sensitive condition. The treatment with buckwheat herb tea is safe and could have a favourable influence on patients with CVI such that further oedema development is prevented.

Sequence and structure requirements for Drosophila tRNA 5'- and 3'-end processing.

Eukaryotic tRNAs are processed at their 5'- and 3'- ends by endonucleases RNase P and 3'-tRNase, respectively. We have prepared substrates for both enzymes, separated the activities from a Drosophila extract, and designed variant tRNAs to assess the effects of sequence and structure on processing. Mutations affect these reactions in similar ways; thus, RNase P and 3'-tRNase probably require similar substrate structures to maintain the catalytic fit. RNase P is more sensitive to substrate substitutions than 3'-tRNase. In three of the four stems, one substitution prevents both processing reactions while the opposite one has less effect; anticodon stem substitutions hardly affect processing, and double substitution intended to restore base pairing also restore processing to the wild type rate. Structure probing suggests that tRNA misfolding sometimes coincides with reduced processing. In other cases, processing inhibition probably results from specific unfavorable stem appositions leading to local helix deformation. A single T loop substitution disrupts the tertiary D-T loop interaction and reduces processing. We have thus begun mapping tRNA processing determinants on the global, local, and tertiary structure levels.

The BLEVE : An update and reexamination of response strategies

The term BLEVE was first used in 1957 by Factory Mutual employees to describe explosions involving violent flast evaporation of pressure liquefied gases upon sudden loss of containment. In the late 1960's and early 1970's the term BLEVE was being heard more and more often, because of a rash of transportation accidents involving LPG's. Since that time several technological improvements have been implemented, and as a result these types of catastrophic accidents are becomming less and less probable. However, BLEVE's still happen, and as long as they do, we need to continuously review, refine and update our procedures and training (AU)

Hypervolemic hemodilution with or without venesection in peripheral arterial occlusive disease stage II.

Patients with peripheral arterial occlusive disease (PAOD) and marked atherosclerosis often present concomitant diseases like coronary heart disease, cerebral circulatory disorders or arterial hypertension. Thus, the extent of hypervolemia is limited in case of an infusion treatment without venesection. Therefore, it was tested whether a hypervolemic hemodilution without venesection is superior to a dilution with venesection in multimorbid patients suffering from PAOD stage II. The colloidal iso-molar solution used was Haes 200/0.5 6%. Both forms of hemodilution were significantly superior compared to a control group well hydrated with cristalloid saline solution; all groups practised walking exercise twice a week over a period of one hour. However, hypervolemic hemodilution without venesection was only slightly better than the dilution with venesection. The walking distance in the group without venesection increased by 68.6 m (36.7%) in the group without venesection, by 59.0 (30.4%) in the group with venesection and by 33.6 m (20.1%) in the control group. The results show that the decision to perform a hyperor isovolemic hemodilution should depend on the volume tolerance of each patient.

Determination of 2-5A synthetase and 2-5A phosphodiesterase in neuroblastoma cells by analytical capillary isotachophoresis: effects of cytokines and comparison with radioenzymatic methods.

2-5A Synthetase and 2-5A phosphodiesterase were determined by analytical capillary isotachophoresis in comparison to radioenzymatic methods. By means of isotachophoretic analysis, a frequently used radioenzymatic 2-5A synthetase assay was optimized and the results of both assays were compared. Using the isotachophoretic assay the influence of interferon-related cytokines (tumor necrosis factor-alpha and interleukin-2) on 2-5A synthetase induction in neuroblastoma cells was estimated. In contrast to mononuclear blood cells, the tumor necrosis factor induced 2-5A synthetase in these cells. 2-5A Phosphodiesterase was determined using an isotachophoretic assay and a radioenzymatic method. Degradation of A2'p5'A2'p5'A (trimeric form of 2-5A core) was measured by isotachophoresis whereas degradation of a mixture of phosphorus-32 labeled 2-5A cores was registered by radioenzymatic assay. Activity of 2-5A phosphodiesterase was only insignificantly enhanced by interferon in mononuclear blood and neuroblastoma cells. In contrast to the radioenzymatic assays, an accurate determination of 2-5A synthetase as well as of 2-5A phosphodiesterase is possible using the isotachophoretic method because the reactions are followed by measuring the substrates ATP and A2'p5'A2'p5'A, respectively.

Poly(U)-binding protein inhibits Drosophila pre-5 S RNA 3'-exonuclease digestion.

A approximately 50-kDa protein binds specifically to the 3' terminus of 135-nucleotide Drosophila pre-5 S RNA. Unlabeled poly(U) competes out protein binding and stimulates the activity of a 3'-exonuclease, which eventually degrades the substrate to 120 nucleotides, the size of mature 5 S RNA. In its RNA binding and UV cross-linking properties, the endogenous poly(U)-binding protein resembles human La, an autoantigen that binds the U > 3 3' ends of vertebrate RNA polymerase III primary transcripts. This protein appears to inhibit a 3' exonuclease and could protect 5 S RNA for faithful processing and transport.

Effects of garlic coated tablets in peripheral arterial occlusive disease.

For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 +/- 65.1 to 207.1 +/- 85.0 m) was significantly higher (P < 0.05) than in the placebo group (by 31 m, from 172.0 +/- 60.9 to 203.1 +/- 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication.