Colon polyps in patients with short bowel syndrome before and after teduglutide: Post hoc analysis of the STEPS study series.

Background & Aims: Teduglutide promotes intestinal growth and is approved for the treatment of short bowel syndrome and intestinal failure (SBS-IF). Based on the pharmacologic activity and preclinical findings, teduglutide can potentially induce proliferative colonic mucosal changes. The aim of this study is to report the occurrence of colorectal polyps in adult patients with SBS-IF who received teduglutide in clinical studies conducted to date.

Approaching the Basis Set Limit of CCSD(T) Energies for Large Molecules with Local Natural Orbital Coupled-Cluster Methods.

Recent optimization efforts and extensive benchmark applications are presented illustrating the accuracy and efficiency of the linear-scaling local natural orbital (LNO) coupled-cluster single-, double-, and perturbative triple-excitations [CCSD(T)] method. A composite threshold combination hierarchy (Loose, Normal, Tight, etc.) is introduced, which enables black box convergence tests and is useful to estimate the accuracy of the LNO-CCSD(T) energies with respect to CCSD(T).

Investigating the Side-Effects of Neem-Derived Pesticides on Commercial Entomopathogenic and Slug-Parasitic Nematode Products Under Laboratory Conditions.

Lethal effects of neem derived pesticides (neem leaf extract (NLE) and NeemAzal-T/S (NA)) were examined on different entomopathogenic (EPN) and slug-parasitic (SPN) nematodes. In our recent study, neem derived pesticides were tested against for the first time under in vitro conditions. Laboratory experiments were set up in 96-well microplates with different concentrations of NLE (0.

Scattering of the Fundamental Shear Guided Wave From a Surface-Breaking Crack in Plate-Like Structures.

Cracks in critical sections of steel structures pose a major safety concern in many industries. Existing high-frequency ultrasonic techniques offer high detection sensitivity to cracks but have poor inspection volume coverage, limiting their practical use for monitoring large areas of structures. Low-frequency guided waves have relatively high inspection area coverage and are currently used in pipeline monitoring for corrosion defects but face challenges in detecting critical cracks that often cause over an order of magnitude lower cross-sectional area loss.

GRP78 translocation to the cell surface and O-GlcNAcylation of VE-Cadherin contribute to ER stress-mediated endothelial permeability.

Increased O-GlcNAcylation, a well-known post-translational modification of proteins causally linked to various detrimental cellular functions in pathological conditions including diabetic retinopathy (DR). Previously we have shown that endothelial activation induced by inflammation and hyperglycemia results in the endoplasmic reticulum (ER) stress-mediated intercellular junction alterations accompanied by visual deficits in a tie2-TNF-α transgenic mouse model. In this study, we tested the hypothesis that increased ER stress via O-GlcNAcylation of VE-Cadherin likely contribute to endothelial permeability.

Facing the Pariah of Science: The Frankenstein Myth as a Social and Ethical Reference for Scientists.

Since its first publication in 1818, Mary Shelley's Frankenstein; or, The Modern Prometheus has transcended genres and cultures to become a foundational myth about science and technology across a multitude of media forms and adaptations. Following in the footsteps of the brilliant yet troubled Victor Frankenstein, professionals and practitioners have been debating the scientific ethics of creating life for decades, never before have powerful tools for doing so been so widely available. This paper investigates how engaging with the Frankenstein myth may help scientists gain a more accurate understanding of their own beliefs and opinions about the social and ethical aspects of their profession and their work.

Management of Vocal Fold Paralysis and Dysphagia for Neurologic Malignancies in Children.

Objectives: To evaluate our experience with a significant number of brain malignancy-related vocal fold paralysis patients and their response to vocal cord-related therapies.

Background: Vocal fold paralysis is a potentially devastating complication of various types of pediatric diseases and surgeries that can lead to significant vocal and swallowing difficulties. While there is significant data in the literature on outcomes of children treated for vocal fold paralysis following cardiac or thyroid surgery, there is a scarcity of such information on children following the treatment of neurologic malignancy.

Measurements for Sulfide-Mediated Inhibition of Myeloperoxidase Activity.

Oxidative stress-alleviating and inflammation-mediatory functions of hydrogen sulfide were reported to be key features of its biological actions. However, the underlying molecular mechanisms of these biological observations are not fully understood. In conditions where sulfide was proposed to be protective against oxidative stress- or inflammation-induced tissue damage (e.

ProPerDP: A Protein Persulfide Detection Protocol.

Persulfide or polysulfide formation on Cys residues is emerging as an abundant protein posttranslational modification, with important regulatory functions. However, as many other Cys oxidative modifications, per- and polysulfides are relatively labile, dynamically interchanging species, which makes their intracellular detections challenging. Here we report our recently developed highly selective method, Protein Persulfide Detection Protocol (ProPerDP), which can detect protein per- and polysulfide species in isolated protein systems, in blood plasma, or in cells and tissue samples.

Blocking tombusvirus replication through the antiviral functions of DDX17-like RH30 DEAD-box helicase.

Positive-stranded RNA viruses replicate inside cells and depend on many co-opted cellular factors to complete their infection cycles. To combat viruses, the hosts use conserved restriction factors, such as DEAD-box RNA helicases, which can function as viral RNA sensors or as effectors by blocking RNA virus replication. In this paper, we have established that the plant DDX17-like RH30 DEAD-box helicase conducts strong inhibitory function on tombusvirus replication when expressed in plants and yeast surrogate host.

Pregnancy and parturition in dromedary camels I. Factors affecting gestation length, calf birth weight and timing of delivery.

In the present study, we evaluated the role of genetic, physiologic and environmental factors in affecting gestation length, calf birth weight and time of parturition in dromedary camels. Reproductive data were collected over a 10-year period at the world's first intensively managed, large-scale camel dairy farm. We hypothesized that environmental conditions (i.

Human liver regeneration following massive hepatic necrosis: Two distinct patterns.

Background And Aim: Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague.

Investigation of ultrasonic backscatter using three-dimensional finite element simulations.

Theoretical models are commonly used to describe ultrasonic backscattering in polycrystalline materials. However, although a full multiple scattering formalism has been derived, due to the difficulty in evaluation, currently only the single and double scattering effects have been evaluated. Three-dimensional finite element (3D FE) models have recently been demonstrated to be capable of predicting ultrasonic attenuation in polycrystalline materials and thereby show great potential in overcoming this limitation.

Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease.

Background And Purpose: Calcification of heart valves is a frequent pathological finding in chronic kidney disease and in elderly patients. Hydrogen sulfide (H S) may exert anti-calcific actions. Here we investigated H S as an inhibitor of valvular calcification and to identify its targets in the pathogenesis.

Reducing the Detrimental Effects of Saturation Phenomena in FRET Microscopy.

Although Förster resonance energy transfer (FRET) is one of the most widely used biophysical methods in biology, the effect of high excitation intensity, leading to donor and acceptor saturation, has not been addressed previously. Here, we present a formalism for the experimental determination of the FRET efficiency at high excitation intensity when saturation of both the donor and the acceptor significantly affect conventional FRET calculations. We show that the proposed methodology significantly reduces the dependence of the FRET efficiency on excitation intensity, which otherwise significantly distorts FRET calculations at high excitation intensities commonly used in experiments.

Comprehensive analysis of how experimental parameters affect HS measurements by the monobromobimane method.

A rapidly increasing number of studies report on widespread biological functions for endogenous hydrogen sulfide. However, the use of multiple, chemically distinct analytical methods to measure free hydrogen sulfide levels in biological samples accumulate data that are not in agreement with each other. In this work a widely appreciated technique, the monobromobimane method, was thoroughly investigated with the overall aims i) to demonstrate how results obtained by different versions of the method should be interpreted and ii) to provide an easy protocol for the community in order to obtain reliable and comparable results.

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

Background And Purpose: ATB-346 is a hydrogen sulfide (H S)-releasing anti-inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti-inflammatory effects. In humans, ATB-346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily).

Molecular Mechanisms and Bioavailability of Polyphenols in Prostate Cancer.

Prostate cancer is the one of the most frequently diagnosed cancers among men over the age of 50. Several lines of evidence support the observation that polyphenols have preventive and therapeutic effects in prostate cancer. Moreover, prostate cancer is ideal for chemoprevention due to its long latency.

Clinical Transcriptome Sequencing Confirms Activation of a Cryptic Splice Site in Suspected -Related Disorder.

encodes a brain-specific Ras GTPase activating protein (GAP) that regulates synaptic strength in glutamatergic neurons. Pathogenic variants in this gene are associated with a neurodevelopmental disorder characterized by intellectual and developmental disabilities, generalized epilepsy, hypotonia, and autism spectrum disorders. We describe a young male with suspected -related disorder given clinical overlap and identification of an intronic variant of uncertain significance; clinical transcriptome analysis demonstrated activation of a cryptic acceptor splice site resulting in frameshift and introduction of a stop codon.

The Uptake and Release of Polysulfur Cysteine Species by Cells: Physiological and Toxicological Implications.

Hydropersulfides and related polysulfides have recently become topics of significant interest due to their physiological prevalence and proposed biological functions. Currently, examination of the effects of hydropersulfide treatment on cells is difficult due to their lack of inherent stability with respect to disproportionation. Herein, it is reported that the treatment of a variety of cell types with cysteine trisulfide (also known as thiocystine; Cys-SSS-Cys), results in an increase in intracellular hydropersulfide levels (e.

Highlighted mechanistic aspects in the chemical biology of reactive sulfur species.

This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.

Polysulfide stabilization by tyrosine and hydroxyphenyl-containing derivatives that is important for a reactive sulfur metabolomics analysis.

The physiological importance of reactive sulfur species (RSS) such as cysteine hydropersulfide (CysSSH) has been increasingly recognized in recent years. We have established a reactive sulfur metabolomics analysis by using RSS metabolic profiling, which revealed appreciable amounts of RSS generated endogenously and ubiquitously in both prokaryotic and eukaryotic organisms. The chemical nature of these polysulfides is not fully understood, however, because of their reactive or complicated redox-active properties.

Recruitment of Vps34 PI3K and enrichment of PI3P phosphoinositide in the viral replication compartment is crucial for replication of a positive-strand RNA virus.

Tombusviruses depend on subversions of multiple host factors and retarget cellular pathways to support viral replication. In this work, we demonstrate that tomato bushy stunt virus (TBSV) and the closely-related carnation Italian ringspot virus (CIRV) recruit the cellular Vps34 phosphatidylinositol 3-kinase (PI3K) into the large viral replication compartment. The kinase function of Vps34 is critical for TBSV replication, suggesting that PI(3)P phosphoinositide is utilized by TBSV for building of the replication compartment.