Spillover of a hepatitis A outbreak among men who have sex with men (MSM) to the general population, the Netherlands, 2017.

Since 2015, outbreaks of hepatitis A among men who have sex with men (MSM) have been reported worldwide. To examine the impact of these MSM outbreaks in the Netherlands, we combined notification and epidemiological data with sequence analysis. Our results show the hazards of outbreaks within risk-groups spilling over into the largely susceptible general population. One third of the outbreak-related hepatitis A virus genotypes were detected in non-MSM cases

Tidal Response to Sea-Level Rise in Different Types of Estuaries: The Importance of Length, Bathymetry, and Geometry

Tidal response to sea-level rise (SLR) varies in different coastal systems. To provide a generic pattern of tidal response to SLR, a systematic investigation was conducted using numerical techniques applied to idealized and realistic estuaries, with model results cross-checked by analytical solutions. Our results reveal that the response of tidal range to SLR is nonlinear, spatially heterogeneous, and highly affected by the length and bathymetry of an estuary and weakly affected by the estuary convergence with an exception of strong convergence. Contrary to the common assumption that SLR leads to a weakened bottom friction, resulting in increased tidal amplitude, we demonstrate that tidal range is likely to decrease in short estuaries and in estuaries with a narrow channel and large low-lying shallow areas

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

New fluoroscopic imaging technique for investigation of 6DOF knee kinematics during treadmill gait

<p>Abstract</p> <p>Introduction</p> <p>This report presents a new imaging technique for non-invasive study of six degrees of freedom (DOF) knee kinematics during treadmill gait.</p> <p>Materials and methods</p> <p>A treadmill was integrated into a dual fluoroscopic imaging system (DFIS) to formulate a gait analysis system. To demonstrate the application of the system, a healthy subject walked on the treadmill at four different speeds (1.5, 2.0, 2.5 and 3.0 MPH) while the DFIS captured the knee motion during three strides under each speed. Characters of knee joint motion were analyzed in 6DOF during the treadmill walking.</p> <p>Results</p> <p>The speed of the knee motion was lower than that of the treadmill. Flexion amplitudes increased with increasing walking speed. Motion patterns in other DOF were not affected by increase in walking speed. The motion character was repeatable under each treadmill speed.</p> <p>Conclusion</p> <p>The presented technique can be used to accurately measure the 6DOF knee kinematics at normal walking speeds.</p

Uterine Artery Embolization in Patients with a Large Fibroid Burden: Long-Term Clinical and MR Follow-up

Uterine artery embolization (UAE) in patients with a large fibroid burden is controversial. Anecdotal reports describe serious complications and limited clinical results. We report the long-term clinical and magnetic resonance (MR) results in a large series of women with a dominant fibroid of >10 cm and/or an uterine volume of >700 cm3. Seventy-one consecutive patients (mean age, 42.5 years; median, 40 years; range, 25–52 years) with a large fibroid burden were treated by UAE between August 2000 and April 2005. Volume reduction and infarction rate of dominant fibroid and uterus were assessed by comparing the baseline and latest follow-up MRIs. Patients were clinically followed at various time intervals after UAE with standardized questionnaires. There were no serious complications of UAE. During a mean follow-up of 48 months (median, 59 months; range, 6–106 months), 10 of 71 patients (14%) had a hysterectomy. Mean volume reduction of the fibroid and uterus was 44 and 43%. Mean infarction rate of the fibroid and overall fibroid infarction rate was 86 and 87%. In the vast majority of patients there was a substantial improvement of symptoms. Clinical results were similar in patients with a dominant fibroid >10 cm and in patients with large uterine volumes by diffuse fibroid disease. In conclusion, our results indicate that the risk of serious complications after UAE in patients with a large fibroid burden is not increased. Moreover, clinical long-term results are as good as in other patients who are treated with UAE. Therefore, a large fibroid burden should not be considered a contraindication for UAE

RetroSnake: A modular pipeline to detect human endogenous retroviruses in genome sequencing data

Human endogenous retroviruses (HERVs) integrated into the human genome as a result of ancient exogenous infections and currently comprise ∼8% of our genome. The members of the most recently acquired HERV family, HERV-Ks, still retain the potential to produce viral molecules and have been linked to a wide range of diseases including cancer and neurodegeneration. Although a range of tools for HERV detection in NGS data exist, most of them lack wet lab validation and they do not cover all steps of the analysis. Here, we describe RetroSnake, an end-to-end, modular, computationally efficient, and customizable pipeline for the discovery of HERVs in short-read NGS data. RetroSnake is based on an extensively wet-lab validated protocol, it covers all steps of the analysis from raw data to the generation of annotated results presented as an interactive html file, and it is easy to use by life scientists without substantial computational training. Availability and implementation: The Pipeline and an extensive documentation are available on GitHub

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Programmable in situ amplification for multiplexed imaging of mRNA expression

In situ hybridization methods enable the mapping of mRNA expression within intact biological samples. With current approaches, it is challenging to simultaneously map multiple target mRNAs within whole-mount vertebrate embryos, representing a significant limitation in attempting to study interacting regulatory elements in systems most relevant to human development and disease. Here, we report a multiplexed fluorescent in situ hybridization method based on orthogonal amplification with hybridization chain reactions (HCR). With this approach, RNA probes complementary to mRNA targets trigger chain reactions in which fluorophore-labeled RNA hairpins self-assemble into tethered fluorescent amplification polymers. The programmability and sequence specificity of these amplification cascades enable multiple HCR amplifiers to operate orthogonally at the same time in the same sample. Robust performance is achieved when imaging five target mRNAs simultaneously in fixed whole-mount and sectioned zebrafish embryos. HCR amplifiers exhibit deep sample penetration, high signal-to-background ratios and sharp signal localization

Electrocautery causes more ischemic peritoneal tissue damage than ultrasonic dissection

Contains fulltext : 96869.pdf (publisher's version ) (Open Access)BACKGROUND: Minimizing peritoneal tissue injury during abdominal surgery has the benefit of reducing postoperative inflammatory response, pain, and adhesion formation. Ultrasonic dissection seems to reduce tissue damage. This study aimed to compare electrocautery and ultrasonic dissection in terms of peritoneal tissue ischemia measured by microdialysis. METHODS: In this study, 18 Wistar rats underwent a median laparotomy and had a peritoneal microdialysis catheter implanted in the left lateral sidewall. The animals were randomly assigned to receive two standard peritoneal incisions parallel to the catheter by either ultrasonic dissection or electrocautery. After the operation, samples of microdialysis dialysate were taken every 2 h until 72 h postoperatively for measurements of pyruvate, lactate, glucose, and glycerol, and ratios were calculated. RESULTS: The mean lactate-pyruvate ratio (LPR), lactate-glucose ratio (LGR), and glycerol concentration were significantly higher in the electrocautery group than in the ultrasonic dissection group until respectively 34, 48, and 48 h after surgery. The mean areas under the curve (AUC) of LPR, LGR, and glycerol concentration also were higher in the electrocautery group than in the ultrasonic dissection group (4,387 vs. 1,639, P=0.011; 59 vs. 21, P=0.008; 7,438 vs. 4,169, P=0.008, respectively). CONCLUSION: Electrosurgery causes more ischemic peritoneal tissue damage than ultrasonic dissection.01 juni 201