Several endoscopic antireflux therapies have been marketed, but long-term data on their objective and clinical efficacy are sparse. This report presents prospective 1-year follow-up results, ...including technical, clinical, and functional success rates, for the first of these treatments to be developed, endoscopic gastroplication (EGP).
A total of 43 EGP procedures were carried out in 38 patients with gastroesophageal reflux disease (GERD). Two or three EndoCinch gastroplications were constructed at the level of the gastric cardia in each patient; five patients were treated twice within 6 - 12 months. Each endoscopic suture joined two gastric folds to each other as a double fold, known as a "gastroplication", in order to narrow the esophagogastric junction. Postprocedure data after 2 months and after 1 year were compared with preoperative data, focusing on symptoms, medication requirements, endoscopic findings, and pH-metry results.
In contrast to the findings at 2 months (which showed that 72 % of the sutures were present and that there was a reduction in the percentage of time when the esophageal pH was < 4 from 15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate failure of the treatment in all 38 patients because none of them still had all of the initially placed gastroplications in situ (90 % of gastroplications were lost). The percentage of patients who did not require proton pump inhibitor medication decreased from 52 % at 2 months to only 20 % at 1 year and even more patients had evidence of reflux esophagitis at 1 year (56 %) than had initially demonstrated signs of this (41 %).
EGP has some short-term beneficial effects on clinical symptoms and pH-metry. However, mainly due to the loss of the endoscopically placed sutures, these effects were not maintained at the 1-year follow-up. EGP cannot therefore be recommended for routine clinical use. Better endoscopic methods need to be developed, and they should be adequately tested before being marketed.
Since mid-2015, there has been an increasing number of chicken samples that are positive for infectious bronchitis virus (IBV) in a screening PCR but which do not show positive results in any ...established, variant-specific PCR tests (793B, QX, D1466, Massachusetts, D274, Italy 02, Arkansas, Variant 2, Q1). Partial sequencing of the viral genome of those samples shows great similarities, but nucleotide similarity in the S1 gene is only about 57%-61% when compared to any other known GI-GVII IBV genotype and lineage. With nucleotide identity in the S1 gene of approximately 80%, the closest related strain in the National Center for Biotechnology Information database (as of March 15, 2020) is the North American PA/1220/98 isolate (AY789942) designated as a unique variant by Valastro
. in 2016. Due to its divergence from other IBV strains, we propose that strain, designated IB80, is the type strain of a novel IBV genotype GVIII. So far, IB80 has been detected in commercial layer and broiler parent flocks, frequently showing severe drops in egg production as well as in broiler flocks in Europe and beyond.
The G2/M checkpoint coordinates DNA replication with mitosis and thereby prevents chromosome segregation in the presence of unreplicated or damaged DNA. Here, we show that the RNA‐binding protein ...TIAR is essential for the G2/M checkpoint and that TIAR accumulates in nuclear foci in late G2 and prophase in cells suffering from replication stress. These foci, which we named G2/M transition granules (GMGs), occur at low levels in normally cycling cells and are strongly induced by replication stress. In addition to replication stress response proteins, GMGs contain factors involved in RNA metabolism as well as CDK1. Depletion of TIAR accelerates mitotic entry and leads to chromosomal instability in response to replication stress, in a manner that can be alleviated by the concomitant depletion of Cdc25B or inhibition of CDK1. Since TIAR retains CDK1 in GMGs and attenuates CDK1 activity, we propose that the assembly of GMGs may represent a so far unrecognized mechanism that contributes to the activation of the G2/M checkpoint in mammalian cells.
Synopsis
The RNA‐binding protein TIAR accumulates in nuclear G2/M transition granules (GMGs) induced by replication stress. During G2/M checkpoint activation TIAR retains CDK1 in GMGs, attenuates CDK1 activity and thereby promotes genome stability.
The RNA‐binding protein TIAR controls mitotic entry and is required for G2/M checkpoint activation independently of the ATR‐Chk1 pathway.
During G2 and prophase, TIAR accumulates in GMGs, nuclear foci that are strongly induced by replication stress.
GMGs contain factors involved in transcription, splicing, DNA replication, DNA repair as well as CDK1/Cyclin B, and may be sites of stalled replication.
During G2/M checkpoint activation, TIAR sequesters CDK1 in GMGs and attenuates CDK1 activity.
The RNA‐binding protein TIAR accumulates in nuclear G2/M transition granules (GMGs) induced by replication stress. During G2/M checkpoint activation TIAR retains CDK1 in GMGs, attenuates CDK1 activity and thereby promotes genome stability.
Although emission inventories are the foundation of air quality management and have supported substantial improvements in North American air quality, they have a number of shortcomings that can ...potentially lead to ineffective air quality management strategies. Major reductions in the largest emissions sources have made accurate inventories of previously minor sources much more important to the understanding and improvement of local air quality. Changes in manufacturing processes, industry types, vehicle technologies, and metropolitan infrastructure are occurring at an increasingly rapid pace, emphasizing the importance of inventories that reflect current conditions. New technologies for measuring source emissions and ambient pollutant concentrations, both at the point of emissions and from remote platforms, are providing novel approaches to collecting data for inventory developers. Advances in information technologies are allowing data to be shared more quickly, more easily, and processed and compared in novel ways that can speed the development of emission inventories. Approaches to improving quantitative measures of inventory uncertainty allow air quality management decisions to take into account the uncertainties associated with emissions estimates, providing more accurate projections of how well alternative strategies may work. This paper discusses applications of these technologies and techniques to improve the accuracy, timeliness, and completeness of emission inventories across North America and outlines a series of eight recommendations aimed at inventory developers and air quality management decision-makers to improve emission inventories and enable them to support effective air quality management decisions for the foreseeable future.
Chromogranin A (CGA) is the major protein of neurosecretory granules (NSG) of cells of the diffuse neuroendocrine system, and the amount of CGA corresponds to the number of NSGs.
Because formalin ...fixation may destroy NSGs, a study was performed to examine the presence of CGA in Merkel cell carcinoma (MCC) to determine whether CGA depends on the presence of intact NSGs.
Formalin-fixed, paraffin-embedded tissue of 15 MCCs was investigated by immunohistochemistry and immunoelectron microscopy for the presence of CGA and NSGs.
CGA was demonstrated in 12 of 15 MCCs by immunochemistry and in 6 of 10 MCCs by immunoelectron microscopy although intact NSGs could not be discerned in all cases.
CGA remains demonstrable even when no morphologically intact NSGs are present, which suggests that CGA is not exclusively responsible for the electron density of NSGs.
AbstractObjectives: To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis.Design: Multicentre, randomised, parallel group, placebo ...controlled trial.Setting: 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom.Participants: Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study.Interventions: Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test.Main outcome measures: Percentage of responders (patients with ≥50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events.Results: At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05).Conclusion: Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction.What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type A was significantly better than placebo on all measures of sweatingPatient satisfaction was high and few adverse events were reportedEffects of treatment remained apparent at 16 weeks
The use of multi-staged exhaust air treatment systems is an effective method of substantially reducing the emission of ammonia, dust particles and odorous substances. Wet filter walls are able to ...absorb large amounts of ammonia when scrubbing fluid containing sulphuric acid is used. In addition, due to their large surface areas and the permanent supply of oxygen and nutrients, wet filter walls provide a basis for the development of biofilms containing nitrogen-converting bacteria. Cyclic nitrification processes could be observed in a two-stage exhaust air treatment system, which had been converted to function as a regulated process control system (elutriation at κ = 20 mS cm(-1); pH 6.5-6.8). With this system, the sulphuric acid requirement was periodically reduced every 6-8 weeks to less than 1 kg H(2)SO(4) per fattening place and year. There was an increased formation of nitrous oxide gas during nitrification after the wet filter stage. Electron-microscopic images of the biofilm growing on the wet filter wall showed aggregates of possible ammonium-oxidising and nitrite-oxidising bacteria.
Exhaust air treatment has gained importance as an essential factor in intensive livestock areas due to the rising emissions in the environment. Wet filter walls of multi-stage exhaust air treatment ...systems precipitate gaseous ammonia and dust particles from exhaust air in washing water. Microbial communities in the biomass developed in the washing water of five large-scale exhaust air treatment units of pig housing facilities, were investigated by fluorescence in situ hybridization (FISH) and 16S rDNA sequence analyses. No "standard" nitrifying bacteria were found in the washing water. Instead mainly α-Proteobacteria, aggregating β- and χ-Proteobacteria, a large number of Actinobacteria, as well as individual Planctomycetales and Crenarchaeota were detected after more than twelve months' operation. The main Proteobacteria species present were affiliated to the families Alcaligenaceae, Comamonadaceae and Xanthomonadaceae. Furthermore, we investigated the consumption of inorganic nitrogen compounds in the washing water of one exhaust air treatment unit during a fattening period with and without pH control. Maintaining the pH at 6.0 resulted in a ca. fivefold higher ammonium concentration and a ca. fourfold lower concentration of oxidized nitrogen compounds after the fattening period was finished.
Summary
Terbinafine (Lamisil) has been registered throughout the world for the treatment of finger and toenail onychomycosis. The recommended duration of treatment of toenail onychomycosis based on ...phase III studies is 12 weeks. This study was designed to determine: (i) if patients in whom the proximal part of the toenails was not affected respond as well after 6 weeks treatment as after 12 weeks treatment; (ii) to identify factors which may allow selection of patients for shorter treatment duration; and (iii) confirm that 6 weeks therapy is sufficient in fingernail mycosis. One hundred and forty‐eight patients received 250 mg terbinafine daily for either 6 or 12 weeks in a double‐ blinded manner, and were followed until 48 weeks after start of therapy. Cure of the nail infection was defined as negative mycological tests (mycological cure) and progressive growth of normal nail (clinical cure). Mycological cure was recorded in 43 of 72 (59.7%) in the 6‐week group and 55 of 76 (72.4%) in the 12‐week group. In those who completed the study per protocol in the 6‐week group. 34 of 61 (55.7%) were cured mycologically corresponding to 46 of 56 (82.1%) in the 12‐week group. The overall clinical and mycological cure rates for the two groups were 28 of 61 (45.9%) and 33 of 56 (58.9%), respectively. In the small number of patients with associated fingernail infection, all were improved and six of eight (75.0%) were cured after a duration of treatment of 6 weeks. A priori risk factors for failure of cure could not be identified in either group. However, shorter duration of disease prior to treatment and no involvement of the big toenail was associated with a trend toward better responses in both groups. It can be concluded from this study that, in toenail mycosis without visible matrix involvement, 6 weeks treatment of terbinafine is generally not sufficient, whereas fingernail infections respond well to this short therapy.
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