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Background and Aims: Patients with sigmoid-type achalasia can be challenging to treat with peroral endoscopic myotomy (POEM). A short myotomy improves technical success; however, outcomes have not previously been evaluated., Methods: This was a multicenter, international, retrospective study of patients who underwent POEM with short (≤4 cm) or standard esophageal myotomy. Outcomes included clinical and technical success, procedural adverse events, and reflux rates., Results: A total of 109 patients with sigmoid achalasia (sigmoid, n = 74; advanced sigmoid, n = 35) underwent POEM across 13 centers (short myotomy, n = 59; standard, n = 50). Technical success was 100% across both groups. Patients who underwent short myotomy had a significantly shorter mean procedure time (57.7 ± 27.8 vs 83.1 ± 44.7 minutes, P = .0005). A total of 6 adverse events were recorded in 6 patients (5.5%; 4 mild, 2 moderate); the adverse event rate was not significantly different between short and standard groups. Ninety-eight patients had follow-up data (median, 3.6 months; interquartile range, 1-14 months). Clinical success was 94% (short, 93%; standard, 95%; P = .70) and did not differ based on achalasia subtype or sigmoid achalasia severity. Twenty-one (22%) patients reported post-POEM reflux and 44% (16 of 36) had objective evidence of pathologic reflux. Rates of pathologic reflux were significantly increased in the standard versus short group (odds ratio, 18.0; 95% confidence interval, 2.0-159.0; P = .009)., Conclusions: POEM with short myotomy is effective and safe for the short-term treatment of sigmoid and advanced sigmoid achalasia. Short myotomy may lead to less reflux than standard myotomy., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Schlachterman: Consultant for Olympus Medical, Fujifilm Healthcare, Boston Scientific, Lumendi, and Laborie. P. Kedia: Consultant for Boston Scientific, Olympus Medical, and Medtronic. R. Pawa: Consultant for Boston Scientific and Cook Medical. P.G. Arcidiacono: Consultant for Pentax Medical, Boston Scientific, and FujiFilm. Advisory Board for MediGlobe and AMBU. S. Nagi: Lecture fees from Falk Pharmaceuticals, Pfizer, and Sanofi. R Sharaiha: Consultant for Boston Scientific, Olympus, and Intuitive Surgical. S. Irani: Consultant for Boston Scientific, Conmed, and Gore. C.-R. Medranda: Key opinion leader for Pentax Medical, Steris, Micro-Tech, G-Tech Medical Supply, EndoSound, and Mdconsgroup. M. Khashab: Consultant for Boston Scientific and Olympus and he receives royalties from Elsevier and UpToDate. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research., (© 2023. The Author(s).)

Argonautes are highly conserved proteins found in almost all eukaryotes and some bacteria and archaea. In humans, there are eight argonaute proteins evenly distributed across two clades, the Ago clade (AGO1-4) and the Piwi clade (PIWIL1-4). The function of Ago proteins is best characterized by their role in RNA interference (RNAi) and cytoplasmic post-transcriptional gene silencing (PTGS) - which involves the loading of siRNA or miRNA into argonaute to direct silencing of genes at the posttranscriptional or translational level. However, nuclear-localized, as opposed to cytoplasmic, argonaute-small RNA complexes may also orchestrate the mechanistically very different process of transcriptional gene silencing, which results in prevention of transcription from a gene locus by the formation of silent chromatin domains. More recently, the role of argonaute in other aspects of epigenetic regulation of chromatin, alternative splicing and DNA repair is emerging. This review focuses on the activity of nuclear-localized short RNA-argonaute complexes in a mammalian setting and discusses recent in vivo studies employing nuclear-directed sRNA for therapeutic interventions. These studies heed the potential development of RNA-based drugs which induce epigenetic changes in the cell.

A method of calibration for real-time quantitative polymerase chain reaction (qPCR) experiments based on the method of standard additions combined with non-linear curve fitting is described. The method is tested by comparing the results of a traditionally calibrated qPCR experiment with the standard additions experiment in the presence of 2 mM EDTA, a known inhibitor chosen to provide an unambiguous test of the principle by inducing an approximately twofold bias in apparent copy number calculated using traditional calibration. The standard additions method is shown to substantially reduce inhibitor-induced bias in quantitative real-time qPCR.

Silencing of individual genes can occur by genetic and epigenetic processes during carcinogenesis, but the underlying mechanisms remain unclear. By creating an integrated prostate cancer epigenome map using tiling arrays, we show that contiguous regions of gene suppression commonly occur through long-range epigenetic silencing (LRES). We identified 47 LRES regions in prostate cancer, typically spanning about 2 Mb and harbouring approximately 12 genes, with a prevalence of tumour suppressor and miRNA genes. Our data reveal that LRES is associated with regional histone deacetylation combined with subdomains of different epigenetic remodelling patterns, which include re-enforcement, gain or exchange of repressive histone, and DNA methylation marks. The transcriptional and epigenetic state of genes in normal prostate epithelial and human embryonic stem cells can play a critical part in defining the mode of cancer-associated epigenetic remodelling. We propose that consolidation or effective reduction of the cancer genome commonly occurs in domains through a combination of LRES and LOH or genomic deletion, resulting in reduced transcriptional plasticity within these regions.

The increased presence of 5-methycytosine at gene promoter regions may be diagnostic of cancer. However, there are many stages in the measurement of gene promoter 5-methylcytosine content where inaccuracies may occur, and this may prevent the use of these measurements for diagnostic or prognostic purposes. A high accuracy LC-MS system was developed for measuring the degree of methylation in two 100 base pair amplicons generated by the polymerase chain reaction (PCR) and in which 5-methylcytidine had been synthetically incorporated. Nucleotide monophosphate reference materials were used to calibrate the peak area ratio of cytidine and 5-methylcytidine to their mole ratio in enzymatic hydrolysates of the amplicons, thus enabling metrological traceability of the methylation ratio to the mole. The methylation values obtained agreed closely with the reference values assigned to the materials. A measurement uncertainty budget was completed and showed that the moisture content of the nucleotide monophosphate reference materials was the largest source of uncertainty in the methylation ratio measurement. Measurement of an oligonucleotide supplied with the materials provided evidence that such materials may be used for calibration of DNA methylation ratios without the need for measurement of moisture content. This raises the possibility that submicrogram amounts of appropriately characterized oligonucleotide reference materials could be used to calibrate methylation ratios obtained by contemporary methodologies (such as PCR after bisulfite conversion of genomic DNA) yielding values that are traceable to the International System of Units (SI). Such calibrated gene methylation measurements would then be internationally comparable as required for effective diagnostic and prognostic measurements.

Various methods have been developed for quantitative analysis of DNA methylation. However, there is currently no reference analysis system regarding DNA methylation with which other analytical approaches can be compared and evaluated. A standard measurement system that includes reference methods and reference materials may improve comparability and credibility of data obtained from different analytical environments. In an effort to establish a standard system for measurement of DNA methylation, the Korea Research Institute of Standards and Science (KRISS) coordinated an international comparison study among different national metrology institutes. An initial stage of the study involved an intercomparison regarding quantitative measurement of total methyl cytosine contents in artificially constructed DNA samples. The measurement principle involved measurement of dNMP contents following enzymatic hydrolysis of DNA samples. Results of the study showed good comparability among four of five participants and close agreement with reference values assigned by the coordinating laboratory. Conflicting data from one participant may have resulted from incomplete hydrolysis of samples due to use of insufficient amounts of enzymes. These results indicate that comparable and accurate results can be obtained from different measurement environments if digestion conditions are controlled appropriately and valid calibration systems are employed.

Omeprazole, a substituted benzimidazole, is an acid pump inhibitor, introduced for treatment of chronic duodenal ulceration. In a study of 116 patients with endoscopically documented chronic duodenal ulcers, omeprazole affected healing in 77 (66.3%) patients after two weeks and 106 (91.4%) patients after four weeks, with symptoms relief in 102 (88%) patients within the first week of treatment. There was significantly higher healing rate in females (p < 0.05) and diffuse ulceration rather than single ulcers (p < 0.05). In meta-analysis comparing omeprazole to other antiulcer drugs reported in this country, there was a significant higher healing rate (p < 0.01) and symptom relief (p < 0.01) in favour of omeprazole. It proved to be effective and safe for the short term treatment of chronic duodenal ulceration.

In a series of 221 patients with various liver diseases studied in Iraq using counterimmunoelectrophoresis and passive haemagglutination techniques, HBsAg was detected in 40.8 per cent of cases with acute viral hepatitis, in 40 per cent in cryptogenic cirrhosis, in 50 per cent in chronic hepatitis, in 100 per cent in active cirrhosis and 71.4 per cent in hepatoma. In acute hepatitis the antigenaemia was highest early in the course of the disease. The duration of antigenaemia ranged from three to 16 weeks. In 3.4 per cent of cases the antigenaemia persisted for more than 35 weeks. In 31.3 per cent of acute hepatitis there was no evidence of parenteral infection.

1811 chronic duodenal ulcers were found amount 1320 patients. These ulcers were classified into four groups, Pyloric (105), Bulbar (953), Apical (723), and Post-Bulbar (30). In 68.3% of cases the ulcer was single and in 31.4% were multiple. 45.8% of ulcers were on the anterior wall, 26.4% on the posterior wall, 26.4% on the lesser curve side and 3.7% on the greater curve side of the duodenum.