Multiplexing PCR allows the identification of within-species genetic diversity in ancient eDNA.

Sedimentary ancient DNA (sedaDNA) has rarely been used to obtain population-level data due to either a lack of taxonomic resolution for the molecular method used, limitations in the reference material or inefficient methods. Here, we present the potential of multiplexing different PCR primers to retrieve population-level genetic data from sedaDNA samples. Vaccinium uliginosum (Ericaceae) is a widespread species with a circumpolar distribution and three lineages in present-day populations. We searched 18 plastid genomes for intraspecific variable regions and developed 61 primer sets to target these. Initial multiplex PCR testing resulted in a final set of 38 primer sets. These primer sets were used to analyse 20 lake sedaDNA samples (11,200 cal. yr BP to present) from five different localities in northern Norway, the Alps and the Polar Urals. All known V. uliginosum lineages in these regions and all primer sets could be recovered from the sedaDNA data. For each sample on average 28.1 primer sets, representing 34.15 sequence variants, were recovered. All sediment samples were dominated by a single lineage, except three Alpine samples which had co-occurrence of two different lineages. Furthermore, lineage turnover was observed in the Alps and northern Norway, suggesting that present-day phylogeographical studies may overlook past genetic patterns. Multiplexing primer is a promising tool for generating population-level genetic information from sedaDNA. The relatively simple method, combined with high sensitivity, provides a scalable method which will allow researchers to track populations through time and space using environmental DNA.

[Structured patient handover in high-risk areas : Evidence and recommendations for the practical implementation]. / Strukturierte Patientenübergabe in Hochrisikobereichen : Evidenz und Empfehlungen für die praktische Implementierung.

The perioperative setting is a high-risk environment which is particularly susceptible to communication deficits and errors. The situation, background, assessment, recommendation (SBAR) approach provides an intuitive guideline for team communication, which is associated with an improved quality of the handover. The German Society for Anaesthesiology and Intensive Care Medicine (DGAI) has updated its recommendations in March 2022 and continues to endorse the use of the SBAR template. The impact of tools used for structured communication during patient handover are often studied in the context of a larger bundle of measures. The SBAR template is one option for establishing structured communication in clinical practice. Successful implementation is supported by clearly defined standard workflows to promote consistent use. This standardization identifies common communication barriers and assists in resolving them in a high-risk environment. A common understanding of the inherent values, and a shared interest in learning, applying, and training these techniques are paramount in establishing a culture of patient safety. This can only be reached through excellent interprofessional teamwork and supportive leadership.

Diffraction-optimized aperiodic surface structures for enhanced current density in organic solar cells.

Novel diffractive surface structures are designed, evaluated, and optimized to achieve a significant increase in current density in organic solar cells. The surface relief phase gratings are patterned based on concentric rings, a Fermat's spiral, and an Archimedean spiral, respectively, and thus diffract incident light independent of its azimuthal angle, as they all exhibit circularly symmetric diffraction patterns. The grating pillars are arranged on the rings or spirals according to periodic or deterministic aperiodic Thue-Morse and Rudin-Shapiro sequences, tailoring the desired diffraction patterns. After evaluating the surface patterns against each other and further parameter optimization, a final current density enhancement of 5 % is achieved for one of the most promising patterns, the Thue-Morse sequence on an Archimedean spiral.

[External Quality Assessment of Thick and Thin Blood Smear Slides for the Diagnosis of Malaria in the Lomé and Gulf Health Districts of Togo]. / Évaluation Externe de la Qualité de la Goutte Épaisse/Frottis Sanguin pour le Diagnostic du Paludisme dans les Districts Sanitaires de Lomé et du Golfe au Togo.

Objective: In sub-Saharan Africa where 90% of malaria cases are concentrated, the control of this disease constitutes a major challenge whose diagnosis by thick and thin smear deserves to be exact and reproducible. The purpose of this study is to assess the performance of thick/thin blood smear in order to improve its implementation process. Material and methods: This was a descriptive and analytical study that took place from May to June 2017 and involved participating laboratories (PL) coming from public, liberal and confessional sectors in Lomé. A set of 13 blood smear slides of variable parasite densities (PD) with assigned values (AV) of parasite densities and the Plasmodium species assigned was used. The criterion for establishing the parasite densities compliance interval was assigned values ± 25% and the performance rates were compared to the 80% recommended by the WHO for Africa region. Results: 41.9% (13/31) of the PLs had a compliance rate greater than 80% including four with a performance of 100% for the ability to identify the Plasmodium species. For the parasitaemia < 100/µl, 51.6% of participating laboratories had a performance rate less than 80% and for parasitaemia > 2000/µl, 100% of these laboratories had a performance rate greater than 80%. Conclusion: The evaluated laboratories had insufficient ability for the identification of Plasmodium falciparum and the correct estimation of low parasitaemia. A need to strength the technical skills, adapted to the context of low parasitaemia are essential to improve the biological diagnosis of malaria in Togo.

[Physiology and clinical importance of white, beige and brown adipose tissue]. / Physiologie und klinische Bedeutung von weißem, beigem und braunem Fettgewebe.

The metabolic functions of different kinds of adipose tissue are of growing scientific and clinical interest. White adipose tissue is not only an energy store but as a highly active endocrine organ it also plays an essential role in the development of diabetes mellitus, dyslipidemia, arterial hypertension and cardiovascular diseases. Brown adipose tissue, on the other hand, can convert chemical energy into heat and could therefore have an opposing, protective effect. The activation of brown adipose tissue and the induction of the development of adipocytes with the characteristics of brown fat cells could make a significant contribution to the treatment of these civilization diseases. This article provides an overview of the current understanding of the physiology and pathophysiology of different adipose tissue types and the resulting therapeutic potential.

[Thyroid medicine for ENT physicians]. / Schilddrüsenmedizin für HNO­Ärzte.

Diseases of the thyroid gland are frequent incidental findings during ultrasound examination of the neck. They affect nearly one third of the normal population. Treatment is not always indicated; however, laboratory diagnostic measures must be initiated to specify the disease. The primary indications for consulting a thyroid specialist are thyroid nodules, goiters, autonomy of the thyroid gland, autoimmune diseases, Graves' disease, and Hashimoto thyroiditis. The aim of this review is to provide an overview of the most important thyroid diseases and their treatment options.

[Structured patient handovers in perioperative medicine : Rationale and implementation in clinical practice]. / Strukturierte Patientenübergabe in der perioperativen Medizin : Rationale und Umsetzung in der klinischen Praxis.

Clear and consistent communication is pivotal for well-functioning teamwork, in operating theatres as well as intensive care units. However, patient handovers significantly vary between specialties and locations. If communication is not well structured, it might increase the risk for mishaps and malpractice. Therefore, implementing structured handover protocols is pivotal. The perioperative setting is a high-risk environment that is prone to communication failures due to operational design (frequent change of shift due to working time restrictions) and a high work load and multitasking (operating room management, short surgery times, concurrent emergencies). Hence teamwork in the operating room and intensive care unit requires clear and consistent communication. In the perioperative setting, the patient is transferred several times: from the ward to operating room, to recovery, intermediate care/intensive care unit and back to normal ward. This necessitates multiple handovers. Since 2005, the World Health Organization (WHO) requests a structured handover concept that processes all relevant information in a predefined order. The SBAR concept (situation, background, assessment, recommendation) is an intuitive communication concept that can improve quality of patient handovers. This underlines the clinical relevance of a structured handover concept that leads to improved outcomes for every patient.In this review, basic measures for a clear and consistent communication are presented. These are pivotal for an effective teamwork and for ensuing patient safety. Furthermore, we will focus on possibilities to implement structured approaches but also on potential barriers of implementation. Communication failure among different health care providers can be identified more easily and hopefully can be eliminated.

Quantitative methods to study epithelial morphogenesis and polarity.

Morphogenesis of an epithelial tissue emerges from the behavior of its constituent cells, including changes in shape, rearrangements, and divisions. In many instances the directionality of these cellular events is controlled by the polarized distribution of specific molecular components. In recent years, our understanding of morphogenesis and polarity highly benefited from advances in genetics, microscopy, and image analysis. They now make it possible to measure cellular dynamics and polarity with unprecedented precision for entire tissues throughout their development. Here we review recent approaches to visualize and measure cell polarity and tissue morphogenesis. The chapter is organized like an experiment. We first discuss the choice of cell and polarity reporters and describe the use of mosaics to reveal hidden cell polarities or local morphogenetic events. Then, we outline application-specific advantages and disadvantages of different microscopy techniques and image projection algorithms. Next, we present methods to extract cell outlines to measure cell polarity and detect cellular events underlying morphogenesis. Finally, we bridge scales by presenting approaches to quantify the specific contribution of each cellular event to global tissue deformation. Taken together, we provide an in-depth description of available tools and theoretical concepts to quantitatively study cell polarity and tissue morphogenesis over multiple scales.

Therapeutic delivery of RNA effectors: diseases affecting the respiratory system.

Although there are several hurdles to overcome on the way to the lung, this target organ provides several advantages for successful drug absorption. Recent findings in this field of research give reason to assume that the pulmonary delivery of RNA effector molecules holds a promising potential for the treatment of numerous severe respiratory diseases.

The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: Report from the SSIEM Adult Metabolic Physicians Group.

BACKGROUND: There are few centres which specialise in the care of adults with inborn errors of metabolism (IEM). To anticipate facilities and staffing needed at these centres, it is of interest to know the distribution of the different disorders. METHODS: A survey was distributed through the list-serve of the SSIEM Adult Metabolic Physicians group asking clinicians for number of patients with confirmed diagnoses, types of diagnoses and age at diagnosis. RESULTS: Twenty-four adult centres responded to our survey with information on 6,692 patients. Of those 6,692 patients, 510 were excluded for diagnoses not within the IEM spectrum (e.g. bone dysplasias, hemochromatosis) or for age less than 16 years, leaving 6,182 patients for final analysis. The most common diseases followed by the adult centres were phenylketonuria (20.6%), mitochondrial disorders (14%) and lysosomal storage disorders (Fabry disease (8.8%), Gaucher disease (4.2%)). Amongst the disorders that can present with acute metabolic decompensation, the urea cycle disorders, specifically ornithine transcarbamylase deficiency, were most common (2.2%), followed by glycogen storage disease type I (1.5%) and maple syrup urine disease (1.1%). Patients were frequently diagnosed as adults, particularly those with mitochondrial disease and lysosomal storage disorders. CONCLUSIONS: A wide spectrum of IEM are followed at adult centres. Specific knowledge of these disorders is needed to provide optimal care including up-to-date knowledge of treatments and ability to manage acute decompensation.

Bulk sensitive hard x-ray photoemission electron microscopy.

Hard x-ray photoelectron spectroscopy (HAXPES) has now matured into a well-established technique as a bulk sensitive probe of the electronic structure due to the larger escape depth of the highly energetic electrons. In order to enable HAXPES studies with high lateral resolution, we have set up a dedicated energy-filtered hard x-ray photoemission electron microscope (HAXPEEM) working with electron kinetic energies up to 10 keV. It is based on the NanoESCA design and also preserves the performance of the instrument in the low and medium energy range. In this way, spectromicroscopy can be performed from threshold to hard x-ray photoemission. The high potential of the HAXPEEM approach for the investigation of buried layers and structures has been shown already on a layered and structured SrTiO3 sample. Here, we present results of experiments with test structures to elaborate the imaging and spectroscopic performance of the instrument and show the capabilities of the method to image bulk properties. Additionally, we introduce a method to determine the effective attenuation length of photoelectrons in a direct photoemission experiment.

[New AHA and ACC guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk : Statement of the D•A•CH Society for Prevention of Cardiovascular Diseases, the Austrian Atherosclerosis Society and the Working Group on Lipids and Atherosclerosis (AGLA) of the Swiss Society for Cardiology]. / Neue AHA- und ACC-Leitlinie zur Risikoreduktion von Herz-Kreislauf-Erkrankungen durch Cholesterinsenkung : Stellungnahme der D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e. V., der Österreichischen Atherosklerose Gesellschaft und der Arbeitsgruppe Lipide und Atherosklerose (AGLA) der Schweizer Gesellschaft für Kardiologie.

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.

[Lipid therapy for patients with coronary heart disease and diabetes. Current state and perspectives]. / Lipidtherapie bei koronarer Herzkrankheit und Diabetes. Gegenwärtiger Stand und Perspektiven.

For patients with diabetes mellitus and coronary heart disease high-dose statin therapy is recommended independent of basal low density lipoprotein (LDL) cholesterol levels and with a target value <70 mg/dl (1.8 mmol/l). Drug combinations which lower LDL, e.g. cholesterol absorption inhibitors, are an option. Fibrates have not been proven to have a cardiovascular advantage but these drugs could be of value in diabetic microangiopathy. A low level of high density lipoprotein (HDL) cholesterol is the most common phenomenon in diabetes. Clinical endpoint studies for the combination with nicotinic acid were negative but therapeutic alternatives are lacking. Therefore, statin therapy is the primary lipid lowering therapy also for diabetic dyslipidemia.

Induction of M2-macrophages by tumour cells and tumour growth promotion by M2-macrophages: a quid pro quo in pancreatic cancer.

INTRODUCTION: More effective therapies are required to improve survival of pancreatic cancer. Possible immunologic targets include tumour associated macrophages (TAMs), generally consisting of M1- and M2-macrophages. We have analysed the impact of TAMS on pancreatic cancer in a syngeneic orthotopic murine model. METHODS: 6606PDA murine pancreatic cancer cells were orthotopically injected into C57BL6 mice. Tumour growth was monitored using MRI. Macrophages were depleted by clodronate liposomes. Tumours including microvessel density were evaluated using immunohistochemistry, immunofluorescence and/or cytometric beads assays. Naïve macrophages were generated employing peritoneal macrophages. In vitro experiments included culturing of macrophages in tumour supernatants as well as tumour cells cultured in macrophage supernatants using arginase as well as Griess assays. RESULTS: Clodronate treatment depleted macrophages by 80% in livers (p = 0.0051) and by 60% in pancreatic tumours (p = 0.0169). MRI revealed tumour growth inhibition from 221.8 mm(3) to 92.3 mm(3) (p = 0.0216). Micro vessel densities were decreased by 44% (p = 0.0315). Yet, MCP-1-, IL-4- and IL-10-levels within pancreatic tumours were unchanged. 6606PDA culture supernatants led to a shift from naïve macrophages towards an M2-phenotype after a 36 h treatment (p < 0.0001), reducing M1-macrophages at the same time (p < 0.037). In vivo, M2-macrophages represented 85% of all TAMs (p < 0.0001). Finally, culture supernatants of M2-macrophages induced tumour growth in vitro by 63.2% (p = 0.0034). CONCLUSIONS: This quid pro quo of tumour cells and M2-macrophages could serve as a new target for future immunotherapies that interrupt tumour promoting activities of TAMs and change the iNOS-arginase balance towards their tumoricidal capacities.

European survey on efficacy and safety of duty-cycled radiofrequency ablation for atrial fibrillation.

AIMS: Duty-cycled radiofrequency ablation (RFA) has been used for atrial fibrillation (AF) for around 5 years, but large-scale data are scarce. The purpose of this survey was to report the outcome of the technique. METHODS AND RESULTS: A survey was conducted among 20 centres from seven European countries including 2748 patients (2128 with paroxysmal and 620 with persistent AF). In paroxysmal AF an overall success rate of 82% [median 80%, interquartile range (IQR) 74-90%], a first procedure success rate of 72% [median 74% (IQR 59-83%)], and a success of antiarrhythmic medication of 59% [median 60% (IQR 39-72%)] was reported. In persistent AF, success rates were significantly lower with 70% [median 74% (IQR 60-92%)]; P = 0.05) as well as the first procedure success rate of 58% [median 55% (IQR 47-81%)]; P = 0.001). The overall success rate was similar among higher and lower volume centres and were not dependent on the duration of experience with duty-cycled RFA (r = -0.08, P = 0.72). Complications were observed in 108 (3.9%) patients, including 31 (1.1%) with symptomatic transient ischaemic attack or stroke, which had the same incidence in paroxysmal and persistent AF (1.1 vs. 1.1%) and was unrelated to the case load (r = 0.24, P = 0.15), bridging anticoagulation to low molecular heparin, routine administration of heparin over the long sheath, whether a transoesophageal echocardiogram was performed in every patient or not and average procedure times. CONCLUSION: Duty-cycled RFA has a self-reported success and complication rate similar to conventional RFA. After technical modifications a prospective registry with controlled data monitoring should be conducted to assess outcome.

Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial.

Recently, in a supplementation study over six months, it has been demonstrated that re-esterified omega-3 fatty acid triacylglycerols (n3-FA-rTAGs) led to a higher increase in omega-3-index compared to identical doses of n3-FA ethyl-esters (n3-FA-EEs), suggesting a better long-term bioavailability. The aim of this study was to examine whether differences occur between the two forms in affecting fasting serum lipid levels. 150 dyslipidemic statin-treated participants were randomized to corn oil as a placebo or fish oil either as rTAG or EE in identical doses (1.01g EPA+0.67g DHA). No changes in total cholesterol, HDL or LDL levels were observed. In the rTAG-group, but not in the EE-group, fasting serum TAG levels were significantly reduced from baseline after three and six months. There was no significant difference between the two n3-FA-groups. However, serum TAG levels were significantly lowered after six months in the rTAG-group compared to the placebo-group in contrast to the EE-group.