Effect of vitamin D replacement on maternal and neonatal outcomes: a randomised controlled trial in pregnant women with hypovitaminosis D. A protocol

Introduction: The vitamin D recommended doses during pregnancy differ between societies. The WHO guidelines do not recommend routine prenatal supplementation, but they underscore the fact that women with the lowest levels may benefit most. The effects of routine supplementation during pregnancy on maternal and neonatal clinical outcomes have not been investigated in the Middle East, where hypovitaminosis D is prevalent. Our hypothesis is that in Middle Eastern pregnant women, a vitamin D dose of 3000?IU/day is required to reach a desirable maternal 25-hydroxyvitamin D [25(OH)D] level, and to positively impact infant bone mineral content (BMC).Methods and analysis: This is a multicentre blinded randomised controlled trial. Pregnant women presenting to the Obstetrics and Gynaecology clinics will be approached. Eligible women will be randomised to daily equivalent doses of cholecalciferol, 600?IU or 3000?IU, from 15 to 18?weeks gestation until delivery. Maternal 25(OH)D and chemistries will be assessed at study entry, during the third trimester and at delivery. Neonatal anthropometric variables and 25(OH)D level will be measured at birth, and bone and fat mass assessment by dual-energy X-ray absorptiometry scan at 1?month. A sample size of 280 pregnant women is needed to demonstrate a statistically significant difference in the proportion of women reaching a 25(OH)D level ?50?nmol/L at delivery, and a difference in infant BMC of 6 (10)g, for a 90% power and a 2.5% level of significance. The proportions of women achieving a target 25(OH)D level will be compared between the two arms, using ?2. An independent t test will be used to compare mean infant BMC between the two arms. The primary analysis is an intention-to-treat analysis of unadjusted results.Ethics and dissemination: The protocol has been approved by the Institutional Review Board at the American University of Beirut-Lebanon (IM.GEHF.22). The trial results will be published in peer-reviewed medical journals and presented at scientific conferences.Trial registration number: NCT02434380.<br/

Conversion of the Mycotoxin Patulin to the Less Toxic Desoxypatulinic Acid by the Biocontrol Yeast Rhodosporidium kratochvilovae Strain LS11

Se describe en este artículo el descubrimiento de la degradación de la micotoxina patulina por una levaduraThe infection of stored apples by the fungus Penicillium expansum causes the contamination of fruits and fruit-derived products with the mycotoxin patulin, which is a major issue in food safety. Fungal attack can be prevented by beneficial microorganisms, so-called biocontrol agents. Previous time-course thin layer chromatography analyses showed that the aerobic incubation of patulin with the biocontrol yeast Rhodosporidium kratochvilovae strain LS11 leads to the disappearance of the mycotoxin spot and the parallel emergence of two new spots, one of which disappears over time. In this work, we analyzed the biodegradation of patulin effected by LS11 through HPLC. The more stable of the two compounds was purified and characterized by nuclear magnetic resonance as desoxypatulinic acid, whose formation was also quantitated in patulin degradation experiments. After R. kratochvilovae LS11 had been incubated in the presence of 13C-labeled patulin, label was traced to desoxypatulinic acid, thus proving that this compound derives from the metabolization of patulin by the yeast. Desoxypatulinic acid was much less toxic than patulin to human lymphocytes and, in contrast to patulin, did not react in vitro with the thiol-bearing tripeptide glutathione. The lower toxicity of desoxypatulinic acid is proposed to be a consequence of the hydrolysis of the lactone ring and the loss of functional groups that react with thiol groups. The formation of desoxypatulinic acid from patulin represents a novel biodegradation pathway that is also a detoxification process

Evolution of the genus Aristolochia (Aristolochiaceae) in the Eastern Mediterranean including the Near East and Caucasia

The Aristolochiaceae are one of the largest angiosperm families, the family has been divided into two subfamilies: Asaroideae, which include Asarum and Saruma, and Aristolochioideae, which includes Thottea sensu lato and Aristolochia sensu lato (Kelly and Gonzales, 2003). Aristolochia sensu lato comprise between 450 and 600 species, distributed throughout the world with centers of diversities in the tropical and subtropical regions (Neinhuis et al., 2005, Wanke et al., 2006a, 2007). However, the extended Mediterranean region including Turkey, the Caucasus and the Near East is likely to be the only diversity hotspot of the genus Aristolochia in the northern hemisphere were up to 60 species and subspecies could be observed (Wanke 2007). Most important contributions to the knowledge of these species were published by Nardi (1984, 1988, 1991, 1993) and Davis &amp; Khan (1961, 1964, 1982), all of these studies were based on morphological characters only. In recent years, with the progress of molecular techniques and in light of the systematic chaos, a detailed study was needed to unravel the evolutionary history prior to a taxonomic revision of this group. The first chapter of my thesis should be regarded as the starting point for more detailed investigation on population level. Preliminary molecular phylogenitic analysis recovered the Mediterranean Aristolochia species as monophyletic (de Groot et al 2006). However, only very few members were included in that study. The latest phylogenetic study by Wanke (2007) dealed with west Mediterranean Aristolochia species and sampled also few members belonging to the east Mediterranean and Caucasian species (3 from Greece, 2 from Georgia and 1 from Turkey). This study reported the Mediterranean Aristolochia species as two molecular and morphologically well supported clades, which were sister to each other. Furthermore, the two closely related species A. sempervirens and A. baetica which have an east west vicariance and are known as Aristolochia sempervirens complex has been recovered as sister group to the remaining west Mediterranean species. A detailed investigation of the evolutionary history of this group is the topic of the second chapter of my thesis (Chapter 2). The Aristolochia sempervirens complex is characterized by an unusual growth form and has a circum Mediterranean distribution. The investigation of these species complex seem to be of great importance to understand speciation and colonization of the Mediterranean by the genus Aristolochia and might shade light in historical evolutionary processes of other plant lineages in the Mediterranean. Furthermore, I test applicability and phylogenetic power of a nuclear single copy gene (nSCG) region to reconstruct well resolved and highly supported gene genealogies as a prerequisite to study evolutionary biology questions in general. Furthermore, a comprehensive overview of leaf epicuticular waxes, hairs and trichomes of 54 species from the old and new world taxa of the genus Aristolochia were investigated using scanning electron microscopy (SEM) to clarify taxonomic status of theses species in contrast to their molecular position. Also this study which is the third chapter of this thesis (Chapter 3), has a strong focus on Mediterranean Aristolochia and tries to provide additional support for molecular findings based on epicuticular waxes and to test them as synapomorphies. Each chapter has its own introduction and abstract resulting in a short general introduction here

Crash dieting: The effects of eating and drinking on driving performance

Previous research suggests that compared to mobile phone use, eating and drinking while driving is more common and is seen as lower risk by drivers. Nevertheless, snacking at the wheel can affect vehicle control to a similar extent as using a hands-free phone, and is actually a causal factor in more crashes. So far, though, there has not been a controlled empirical study of this problem. In an effort to fill this gap in the literature, we used the Brunel University Driving Simulator to test participants on a typical urban scenario. At designated points on the drive, which coincided with instructions to eat or drink, a critical incident was simulated by programming a pedestrian to walk in front of the car. Whilst the driving performance variables measured were relatively unaffected by eating and drinking, perceived driver workload was significantly higher and there were more crashes in the critical incident when compared to driving normally. Despite some methodological limitations of the study, when taken together with previous research, the evidence suggests that the physical demands of eating and drinking while driving can increase the risk of a crash

Kinetic analysis of mouse brain proteome alterations following chikungunya virus infection before and after appearance of clinical symptoms

Recent outbreaks of Chikungunya virus (CHIKV) infection have been characterized by an increasing number of severe cases with atypical manifestations including neurological complications. In parallel, the risk map of CHIKV outbreaks has expanded because of improved vector competence. These features make CHIKV infection a major public health concern that requires a better understanding of the underlying physiopathological processes for the development of antiviral strategies to protect individuals from severe disease. To decipher the mechanisms of CHIKV in

Altered Protein Networks and Cellular Pathways in Severe West Nile Disease in Mice

Background:The recent West Nile virus (WNV) outbreaks in developed countries, including Europe and the United States, have been associated with significantly higher neuropathology incidence and mortality rate than previously documented. The changing epidemiology, the constant risk of (re-)emergence of more virulent WNV strains, and the lack of effective human antiviral therapy or vaccines makes understanding the pathogenesis of severe disease a priority. Thus, to gain insight into the pathophysiological processes in severe WNV infection, a kinetic analysis of protein expression profiles in the brain of WNV-infected mice was conducted using samples prior to and after the onset of clinical sympt

Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future.

The interest in RDN for hypertension has fluctuated recently, with a flurry of initial enthusiasm followed by sudden loss of interest by researchers and device manufacturers, with an almost as sudden resurgence in clinical trials activity and device innovation more recently. There is widespread consensus that this therapeutic strategy can be effective, at least for some of the technologies available. Major uncertainties remain as to the clinical role of RDN, and whether any of the emerging technologies such as AV-anastomosis formation, carotid body ablation, carotid bulb expansion, or baroreflex stimulation will have a future as effective treatment options in patients with hypertension. In our first consensus report in 2015, the European Expert Group pointed to the major unmet need of standardization of measurements, trial design and procedural performance.6 With the large number of different technologies currently in the pipeline, this need has even increased. Only through high-quality, collaborative research and openness to new methods for recruitment, patient selection, and assessment of outcomes will it be possible to establish incontrovertibly whether device therapies for hypertension are effective and what are preferred patient populations. Once the proof of concept is established, further studies with a design relevant to clinical reality will be needed to establish the place of new devices in the treatment armoury. The clinical and research community has a large responsibility to prove or disprove the value of new therapies, in order to ensure that antihypertensive devices provide future patients with the greatest benefit and the smallest risk. copy; The Author 2017

Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension

Renal denervation (RDN) is a treatment option for patients with hypertension resistant to conventional therapy. Clinical trials have demonstrated variable benefit. To understand the determinants of successful clinical response to this treatment, we integrated porcine and computational models of intravascular radiofrequency RDN. Controlled single-electrode denervation resulted in ablation zone geometries that varied in arc, area, and depth, depending on the composition of the adjacent tissue substructure. Computational simulations predicted that delivered power density was influenced by tissue substructure, and peaked at the conductivity discontinuities between soft fatty adventitia and water-rich tissues (media, lymph nodes, etc.), not at the electrode-tissue interface. Electrode irrigation protected arterial wall tissue adjacent to the electrode by clearing heat that diffuses from within the tissue, without altering periarterial ablation. Seven days after multielectrode treatments, renal norepinephrine and blood pressure were reduced. Blood pressure reductions were correlated with the size-weighted number of degenerative nerves, implying that the effectiveness of the treatment in decreasing hypertension depends on the extent of nerve injury and ablation, which in turn are determined by the tissue microanatomy at the electrode site. These results may explain the variable patient response to RDN and suggest a path to more robust outcomes.National Institutes of Health (U.S.) (NIH grant R01 GM-49039

Das chronische Subduralhämatom

Objective: Das cSDH bezeichnet die Ansammlung eines verflüssigten Hämatoms im subduralen Raum. Ziel der Therapie des cSDH sollte die möglichst wenig invasive, aber suffiziente Entlastung sein. In dieser Arbeit wird das 3-Stufen-Konzept in der Behandlung des cSDH vorgestellt. Methoden: Im Rahmen der Studie wurden retrospektiv die Daten von 163 Patienten erhoben, Hierbei wurden aktuelle Anamnese Risikofaktoren und Vorerkrankungen erfasst. Der Behandlungsverlauf, Komplikationen, Rezidive und die jeweilige Art der Operation. Schlussfolgerungen: Die Bohrlochtrepanation bleibt der Goldstandard bei der Entlastung des cSDH, zumindest als erste operative Maßnahme, auch beim 1. Rezidiv eines cSDH eine Bohrlochtrepanation erfolgen sollte. Beim 2. Rezidiv sprechen die Ergebnisse für die Empfehlung zur Entlastung über Kraniotomie. In einzelnen Fällen (z. B. dicker, septierter Hämatomkapsel, Hirnödem, frischen Blutanteilen) ist es sinnvoll bei der erstoperation eine Kraniotomie anzustreben