In silico Mechanics of Stem Cells Intramyocardially Transplanted with a Biomaterial Injectate for Treatment of Myocardial Infarction.

PURPOSE: Biomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart. METHODS: A microstructural finite element model of a mid-wall infarcted myocardial region was developed from ex vivo microcomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa. RESULTS: The transplanted cells' deformation was largest for Einj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einj changes for softer (Einj ≤ 738 kPa) than stiffer biomaterials. CONCLUSIONS: Combining the microstructural and biventricular finite element models enables quantifying micromechanics of transplanted cells in the heart. The approach offers a broader scope for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

Picosecond-Scale Ultrafast Many-Body Dynamics in an Ultracold Rydberg-Excited Atomic Mott Insulator.

We report the observation and control of ultrafast many-body dynamics of electrons in ultracold Rydberg-excited atoms, spatially ordered in a three-dimensional Mott insulator (MI) with unity filling in an optical lattice. By mapping out the time-domain Ramsey interferometry in the picosecond timescale, we can deduce entanglement growth indicating the emergence of many-body correlations via dipolar forces. We analyze our observations with different theoretical approaches and find that the semiclassical model breaks down, thus indicating that quantum fluctuations play a decisive role in the observed dynamics. Combining picosecond Rydberg excitation with MI lattice thus provides a platform for simulating nonequilibrium dynamics of strongly correlated systems in synthetic ultracold atomic crystals, such as in a metal-like quantum gas regime.

Findings of illicit drugs in hair of children at different ages.

Hair is a preferred material to detect exposure or use of illegal drugs in children. In the present study, we investigated a total of 387 hair samples for commonly applied illegal drugs of children up to 16 years. Analysis was by liquid chromatography/mass spectrometry with LOQs of 0.01 ng/mg hair for all analytes except tetrahydrocannabinol carboxylic acid with an LOQ of 0.1 pg/mg hair. Results were firstly compared with our in-house statics on results from adults' hair, and secondly to literature data. We started from the assumption that drug concentrations decrease with increasing age.Results were assigned to 4 different age groups (< 1 year, 1-< 6 years, 6-< 14 years, 14-16 years). As expected, higher results were obtained in age groups 1 and 2. The lowest concentrations were present in age group 3, whereas an increase could be observed in group 4 except heroin. In babies, positive results may be due to in utero exposure, breast milk feeding, and a close physical contact. All drugs under investigation such as cannabinoids, cocaine, amphetamines, and opiates have been detected in breast milk as well as in skin excretions such as sebum, sweat and cutaneous cells. For most drugs, average concentrations in children hair were lower than in adult hair when compared with our in-house statistics. Interestingly, the increase of cannabinoids, cocaine, and amphetamines concentrations in adolescents' hair points to a deliberate use of these drugs possibly in addition to passive exposure. This observation shows that age groups 1 and 4 are most vulnerable if caregivers or parents are drug users, even if the sources of positive drug findings differ.

Implementation and operation of a fiber-coupled CMOS detector in a low energy electron Microscope.

The intrinsically weak signals in ultrafast electron microscopy experiments demand an improvement in the signal-to noise ratio of suitable electron detectors. We provide an experience report describing the installation and operation of a fiber-coupled CMOS based detector in a low energy electron microscope. We compare the detector performance to the traditional multi-channel-plate-based setup. The high dynamic range CMOS detector is capable of imaging spatially localized large intensity variations with low noise. The detector is blooming-free and overexposure appears uncritical. Overall, we find dramatic improvements in the imaging with the fiber-coupled CMOS detector compared to imaging with our previously used multi-channel-plate detector.

Biological Efficacy and Safety of Niacinamide in Patients With ADPKD.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst enlargement, leading to kidney failure. Sirtuin-1 is upregulated in ADPKD and accelerates disease progression by deacetylating p53. Niacinamide is a dietary supplement that inhibits sirtuins at high doses. METHODS: We conducted an open-label, single-arm intervention trial (study 1, N = 10), and a randomized, double blinded, placebo-controlled trial (study 2, N = 36) to assess the biological activity and safety of niacinamide. Patients with ADPKD were given 30 mg/kg oral niacinamide or placebo, for 12 months. The primary endpoint was the ratio of acetylated p53 to total p53 protein in peripheral blood mononuclear cells (PBMCs). RESULTS: There was no sustained effect of niacinamide on acetylated/total p53 in either study and no difference between placebo and niacinamide arms. There was no difference in the change in height-adjusted total kidney volume over 12 months between niacinamide and placebo. Niacinamide was generally well tolerated. The most common adverse effects were nausea, diarrhea, gastroesophageal reflux, headache, and acneiform rash but there was no difference in their incidence between niacinamide and placebo. CONCLUSIONS: In conclusion, niacinamide is safe and well-tolerated in patients with ADPKD. However, we were unable to detect a sustained inhibition of sirtuin activity over 12 months of treatment, and there was no signal to suggest a beneficial effect on any efficacy measure.

Concentration distribution of more than 100 drugs and metabolites in forensic hair samples.

Drug testing in hair can complement conventional blood and urine analysis as it enlarges the window of detection and may allow a differentiation of heavy from moderate or rare use. Databases of drug concentrations in biological matrices are a valuable support in interpreting analytical results. In forensic toxicology, several databases exist especially for blood/serum samples. In the present paper, the concentration distributions of more than 100 legal and illegal drugs such as narcotic drugs, opioids, antidepressants, antipsychotics, benzodiazepines, and major metabolites detected in authentic Caucasian hair samples in our laboratory are summarized. Depending on availability, the proximal sections of 1-6 cm in length were analyzed by liquid chromatography/tandem mass spectrometry following extraction of the finely chopped specimens by ultrasound in methanol. The data may present a helpful basis also for other laboratories for an initial evaluation of their results. However, these statistical data should not be used uncritically without including the circumstances of the particular case and the analytical procedures used. In addition, each laboratory in charge of interpreting results from hair analysis should balance own results as far as available with this data base.

[Importance of magnetic resonance imaging/ultrasound-guided fusion biopsy for the detection and monitoring of prostate cancer]. / Stellenwert der MRT/Ultraschall-Fusionsbiopsie für die Detektion und Verlaufskontrolle des Prostatakarzinoms.

The use of multiparametric magnetic resonance imaging (mpMRI) is becoming increasingly more important for the primary diagnostics of prostate cancer (PCa) and for monitoring under active surveillance. Current studies confirmed that the use of mpMRI can increase the detection of clinically significant PCa and reduce the detection rate of insignificant PCa as well as the rate of unnecessary biopsies. The information from mpMRI can be cognitively used for in-bore biopsy and using fusion biopsy systems. There are no clear recommendations on the access approach for fusion biopsy (e. g. transrectal or perineal), whereby higher rates of rectal bleeding and infections have been described for transrectal access compared to perineal access. The increasing rate of antibiotic resistance as well as restricted indications for the use of quinolones are a major challenge for transrectal biopsy.

Analysis of a newly discovered antigen of Bacillus cereus biovar anthracis for its suitability in specific serological antibody testing.

AIMS: The aim of this work was to identify a protein which can be used for specific detection of antibodies against Bacillus cereus biovar anthracis (Bcbva), an anthrax-causing pathogen that so far has been described in African rainforest areas. METHODS AND RESULTS: Culture supernatants of Bcbva and classic Bacillus anthracis (Ba) were analysed by gel electrophoresis, and a 35-kDa protein secreted only by Bcbva and not Ba was detected. The protein was identified as pXO2-60 by mass spectrometry. Sequence analysis showed that Ba is unable to secrete this protein due to a premature stop codon in the sequence for the signal peptide. Immunization of five outbred mice with sterile bacterial culture supernatants of Bcbva revealed an immune response in ELISA against pXO2-60 (three mice positive, one borderline) and the protective antigen (PA; four mice). When supernatants of classic Ba were injected into mice or human sera from anthrax patients were analysed, only antibodies against PA were detected. CONCLUSIONS: In combination with PA, the pXO2-60 protein can be used for the detection of antibodies specific against Bcbva and discriminating from Ba. SIGNIFICANCE AND IMPACT OF THE STUDY: After further validation, serological assays based on pXO2-60 can be used to perform seroprevalence studies to determine the epidemiology of B. cereus bv anthracis in affected countries and assess its impact on the human population.

Effect of intra-myocardial Algisyl-LVR™ injectates on fibre structure in porcine heart failure.

Recent preclinical trials have shown that alginate injections are a promising treatment for ischemic heart disease. Although improvements in heart function and global structure have been reported following alginate implants, the underlying structure is poorly understood. Using high resolution ex vivo MRI and DT-MRI of the hearts of normal control swine (n = 8), swine with induced heart failure (n = 5), and swine with heart failure and alginate injection treatment (n = 6), we visualized and quantified the fibre distribution and implant material geometry. Our findings show that the alginate injectates form solid ellipsoids with a retention rate of 68.7% ±â€¯21.3% (mean ±â€¯SD) and a sphericity index of 0.37 ±â€¯0.03. These ellipsoidal shapes solidified predominantly at the mid-wall position with an inclination of -4.9°â€¯±â€¯31.4° relative to the local circumferential direction. Overall, the change to left ventricular wall thickness and myofiber orientation was minor and was associated with heart failure and not the presence of injectates. These results show that alginate injectates conform to the pre-existing tissue structure, likely expanding along directions of least resistance as mass is added to the injection sites. The alginate displaces the myocardial tissue predominantly in the longitudinal direction, causing minimal disruption to the surrounding myofiber orientations.

Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. METHODS: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin-angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR) > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI) measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. RESULTS: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both). Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively). CONCLUSION: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI.

Endothelial cells on an aged subendothelial matrix display heterogeneous strain profiles in silico.

Within the artery intima, endothelial cells respond to mechanical cues and changes in subendothelial matrix stiffness. Recently, we found that the aging subendothelial matrix stiffens heterogeneously and that stiffness heterogeneities are present on the scale of one cell length. However, the impacts of these complex mechanical micro-heterogeneities on endothelial cells have not been fully understood. Here, we simulate the effects of matrices that mimic young and aged vessels on single- and multi-cell endothelial cell models and examine the resulting cell basal strain profiles. Although there are limitations to the model which prohibit the prediction of intracellular strain distributions in alive cells, this model does introduce mechanical complexities to the subendothelial matrix material. More heterogeneous basal strain distributions are present in the single- and multi-cell models on the matrix mimicking an aged artery over those exhibited on the young artery. Overall, our data indicate that increased heterogeneous strain profiles in endothelial cells are displayed in silico when there is an increased presence of microscale arterial mechanical heterogeneities in the matrix.

Lucerne cast - LuCa: Functional conservative treatment of extra-articular fractures of the proximal phalanges of the fingers (with video).

Most extra-articular fractures of the proximal phalanges (P1) of the triphalangeal fingers can be treated conservatively with good results. Prerequisites for successful fracture treatment are intact soft tissue without any lesions of the extensor hood and stable initial fracture reduction. The key to functional conservative treatment of P1 fractures is to immobilize the metacarpophalangeal joints in flexion, resulting in equilibrium of flexor and extensor forces across the fracture site, which converts these inherently unstable fractures into relatively stable fractures. Precise initial application of the cast and regular follow-up of the patient is essential for successful treatment. By means of an instructional video, an overview of the equipment required is given, and the correct application of a Lucerne Cast is illustrated step-by-step.

Subjective and Electroretinographic Dynamics of Light Adaptation in the Human Visual System.

The excitation of the visual system increases with increasing retinal illumination. At the same time, the sensitivity of the system decreases (light adaptation). Higher excitation automatically results in a lower sensitivity. This study investigates whether this antagonistic relationship between excitation and sensitivity also applies to the dynamic case, that is, during the transition to a higher excitation level after a sudden increase in retinal illuminance. For this purpose, the courses of the subjective and the electroretinographic threshold in the transitional period during and after a step of the adaptation illuminance were investigated by means of a special light-stimulation system. The investigation was carried out on 9 (subjective threshold) and 12 (electroretinographic threshold) subjects. As a measure of the course of the excitation during this time, the response ERG on the adaptation step was recorded. With the step in adaptation light, the thresholds show a rapid increase, which starts already about 0.1 s before the step. This is followed, within the next second, by a threshold decrease to a new plateau above the initial level. The comparison between the response ERG on the adaptation step and the course of the electroretinographic increment threshold during this time shows a broad agreement between the two courses. Thus, it can be assumed that the sensitivity of the visual system also follows the excitation in the dynamic case. In addition, the investigation shows that the glare experienced after a step in illuminance apparently shows great subjective differences.

A validated patient-specific FSI model for vascular access in haemodialysis.

The flow rate inside arteriovenous fistulas is many times higher than physiological flow and is accompanied by high wall shear stress resulting in low patency rates. A fluid-structure interaction finite element model is developed to analyse the blood flow and vessel mechanics to elucidate the mechanisms that can lead to failure. The simulations are validated against flow measurements obtained from magnetic resonance imaging data.

Discovery of the first ichthyosaur from the Jurassic of India: Implications for Gondwanan palaeobiogeography.

An articulated and partially preserved skeleton of an ichthyosaur was found in the Upper Jurassic (Upper Kimmeridgian) Katrol Formation exposed at a site south of the village Lodai in Kachchh district, Gujarat (western India). Here we present a detailed description and inferred taxonomic relationship of the specimen. The present study revealed that the articulated skeleton belongs to the family Ophthalmosauridae. The new discovery from India further improves the depauperate fossil record of ichthyosaurs from the former Gondwanan continents. Based on the preserved length of the axial skeleton and anterior part of the snout and taking into account the missing parts of the skull and postflexural region, it is suggested that the specimen may represent an adult possibly reaching a length of 5.0-5.5 m. The widespread occurrence of ophthalmosaurids in the Upper Jurassic deposits of western Tethys, Madagascar, South America and India points to possible faunal exchanges between the western Tethys and Gondwanan continents through a southern seaway.

The EIGER detector for low-energy electron microscopy and photoemission electron microscopy.

EIGER is a single-photon-counting hybrid pixel detector developed at the Paul Scherrer Institut, Switzerland. It is designed for applications at synchrotron light sources with photon energies above 5 keV. Features of EIGER include a small pixel size (75 µm × 75 µm), a high frame rate (up to 23 kHz), a small dead-time between frames (down to 3 µs) and a dynamic range up to 32-bit. In this article, the use of EIGER as a detector for electrons in low-energy electron microscopy (LEEM) and photoemission electron microscopy (PEEM) is reported. It is demonstrated that, with only a minimal modification to the sensitive part of the detector, EIGER is able to detect electrons emitted or reflected by the sample and accelerated to 8-20 keV. The imaging capabilities are shown to be superior to the standard microchannel plate detector for these types of applications. This is due to the much higher signal-to-noise ratio, better homogeneity and improved dynamic range. In addition, the operation of the EIGER detector is not affected by radiation damage from electrons in the present energy range and guarantees more stable performance over time. To benchmark the detector capabilities, LEEM experiments are performed on selected surfaces and the magnetic and electronic properties of individual iron nanoparticles with sizes ranging from 8 to 22 nm are detected using the PEEM endstation at the Surface/Interface Microscopy (SIM) beamline of the Swiss Light Source.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

[Management of ureteral strictures and hydronephrosis]. / Management von Harnleiterstrikturen und Harnstauung.

Patients who develop hydronephrosis due to an acute cause often have colic-like pain but hydronephrosis secondary to a chronic cause is often asymptomatic. Ureteral obstruction can be due to a variety of intrinsic and extrinsic causes, such as trauma, radiation, iatrogenic injury, urolithiasis, malignancies and congenital causes. Management planning is dictated by the underlying cause, patient comorbidity and life expectancy. Malignant ureteral obstructions can be managed with segmental metal stents with advantages in the quality of life and provide an alternative to long-term treatment with a DJ stent. Endoscopic balloon dilatation and endoureterotomy are options for benign ureteral strictures up to 2 cm in length. For longer benign strictures there are a number of reconstructive techniques, which can also be performed by laparoscopic or robot-assisted approaches at specialized centers.

Endoscopically assisted proximal radial nerve decompression: surgical technique.

STATE OF THE ART: The proximal radial nerve compression syndrome includes supinator syndrome and proximal radial nerve constrictions. This article presents a new endoscopic assisted radial nerve decompression surgical technique described for the first time by Leclère et al. in 2013. SURGICAL TECHNIQUE: Endoscopic scissor decompression of the proximal radial nerve is always performed under plexus anaesthesia. It includes 8 key steps documented in this article. We review the indications and limitations of the surgical technique. CONCLUSION: Early clinical results after endoscopic assisted decompression of the radial nerve appear excellent. However, they still need to be compared with conventional techniques. Clinical studies are likely to widely develop because of the mini-invasive nature of this new surgical technique.