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 & 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

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

Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany.

In Germany, ~8 million patients take angiotensin receptor blockers (ARBs) and 2.25 million of them valsartan. In 2018, contamination of generic ARBs with probable carcinogenic nitrosamines resulted in more than 30 recalls. The impact of such a huge recall has never been explored in Europe. We analyzed the utilization of valsartan, all ARBs, and other alternative antihypertensive drugs in Germany. We used our database of anonymized dispensing data from >80% of community pharmacies at the expense of the statutory health insurance (SHI) funds from January 2017 to December 2019. We analyzed 290.8 million prescriptions, including all oral mono- and fixed-dose combinations of ARBs and plausible alternatives, i.e. ACE inhibitors (ACEi), beta-blockers (BB), and calcium channel blockers (CCB). Utilization was calculated by defined daily doses per 1000 SHI-insured persons per day (DID). Valsartan use decreased substantially after the recalls in July 2018 from 39.0 to 14.2 DID (-64%) in the second quarter of 2019 and to 16.9 DID (-57%) in the fourth quarter of 2019. Simultaneously, the use of alternative ARBs increased from 77.7 DID in the second quarter of 2018 to 121.9 DID (+57%) in the fourth quarter of 2019, mainly due to an increase of candesartan dispensing to 99.8 DID (+73%). There were no changes in the utilization of ACEi, BB, or CCB. The majority of recalled generic valsartan products were replaced by other ARBs, predominantly candesartan, despite documented drug shortages. In contrast to previous safety warnings/recalls, our data do not suggest an under-prescription of antihypertensives during this period

Pneumothorax complicating isolated clavicle fracture

Isolated clavicle fractures are among the commonest of traumatic fractures in the emergency department. Complications of isolated clavicle fractures are rare. Pneumothorax has been described as a complication of a fractured clavicle only rarely in English literature. In all the reported cases, the pneumothorax was treated by a thoracostomy and the clavicle fracture was treated conservatively. In our case, the pneumothorax required a chest drain insertion and the clavicle fracture was treated surgically with good result

Closing the gap : development of an analytical methodology using volumetric absorptive microsampling of finger prick blood followed by LC-HRMS/MS for adherence monitoring of antihypertensive drugs

Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is a promising tool for adherence monitoring. This study focused on development of an analytical methodology to improve VAMS-based strategies for adherence assessment by analyzing angiotensin-converting-enzyme (ACE) inhibitors, loop diuretics, a potassium-sparing diuretic, and a thiazide diuretic. Development included sample preparation, chromatographic conditions, mass spectrometry settings, validation, and demonstrating proof of concept. Quantifcation of analytes, by name furosemide, hydrochlorothiazide, lisinopril, torasemide, and the active metabolites, canrenone, enalaprilat, and ramiprilat in fnger prick blood (FPB), was validated based on international guidelines. Selectivity, carryover, and within/between-run accuracy and precision were in accordance with the recommendations. The matrix efect was evaluated at three diferent hematocrit levels (HT: 20%, 40%, 60%) and the coefcients of variation did not exceed 15%. Dilution integrity (1:10 and 1:20) was given for all analytes except lisinopril, yet for lisinopril, the therapeutic range was already covered by the calibration range. Long-term stability in VAMS tips was tested for 2 weeks at 24 °C in the dark and revealed no degradation of analytes. The proof of concept was performed by analyzing 35 intakes of ACE-inhibitors and diuretics in 18 VAMS and matched plasma samples. Hereby, determined concentration in FPB and plasma cannot be used interchangeably, and thus specifc reference ranges for whole blood must be established. Nevertheless, the VAMS-based strategy was shown to be suitable for assessing adherence of all classes of antihypertensive drugs used in the guidelines to manage hypertension

Primary non-Hodgkin’s lymphoma of the bladder: case report and literature review

Primary non-Hodgkin's lymphoma (NHL) of the bladder is a very rare entity. The clinical, radiological and endoscopic signs are not specifics. The diagnosis is exclusively histological. Chemotherapy, radiotherapy and surgery are the different therapeutic options used either alone or in combination. We report a 57 years old patient treated with chemotherapy (6 cycles of R-CHOP) for primary NHL of the bladder with a complete response while discussing the different specificities of this disease.Key words: Primary lymphoma, Non-Hodgkin’s lymphoma, Bladder, Chemotherap

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/

Enhanced Cerenkov Second-Harmonic Generation in Patterned Lithium Niobate

We present experimental results of second harmonic generation enhancement through the resonance of the band edge in a photonic crystal based on lithium niobate. Proton exchange technique was used to fabricate a waveguide near the surface of the lithium niobate substrate. The photonic crystal structure over the waveguide was made by UV laser interferometry. Subsequently experiments were designed to quantify the Cerenkov second-harmonic generation (CSHG) radiated into the substrate. The SHG radiated inside the waveguides was also experimentally investigated. In our experiments, the second guided mode of the waveguide was tuned to the band edge resonance to enhance the second harmonic generation. The highest conversion efficiency of CSHG using photonic band gap (PBG) was around 50 times compared to SHG emission from non-patterned lithium niobate. A numerical model was used to corroborate the experimental result. It was also found that the SHG signal in the waveguides is quenched compared to the CSHG signal