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Background: Gastric non-Helicobacter pylori Helicobacter (NHPH) species naturally associated with animals have been linked with gastric disease in human patients., Aim: The prevalence and clinical significance of zoonotic gastric NHPHs was determined in large and well-defined, H. pylori-negative, gastric patient populations., Methods: Patients were retrospectively (n = 464) and prospectively (n = 65) included for gastric biopsy collection: chronic gastritis (CG), peptic ulcer disease and gastric MALT lymphoma, without identified aetiology. PCR and sequencing was performed for the detection of gastric Helicobacter species. Retrospectively, asymptomatic gastric bypass patients (n = 38) were included as controls. Prospectively, additional saliva samples and symptom and risk factor questionnaires were collected. In this group, patients with gastric NHPH infection were administered standard H. pylori eradication therapy and underwent follow-up gastroscopy post-therapy., Results: In the retrospective samples, the prevalence of gastric NHPHs was 29.1%, while no gastric NHPHs were detected in control biopsies. In the prospective cohort, a similar proportion tested positive: 27.7% in gastric tissue and 20.6% in saliva. The sensitivity and accuracy for the detection of gastric NHPHs in saliva compared to gastric tissue was 27.8% and 69.8% respectively. Following eradication therapy, clinical remission was registered in 12 of 17 patients, histological remission in seven of nine and eradication in four of eight patients., Conclusion: These findings suggest a pathophysiological involvement of NHPHs in gastric disease. Patients presenting with gastric complaints may benefit from routine PCR testing for zoonotic gastric NHPHs., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Purpose: Laparoscopic liver resection (LLR) has gained acceptance as an effective treatment for colorectal liver metastases (CRLM) in selected patients, providing similar oncologic outcomes compared to open liver resection (OLR). The aim of this study was to determine prognostic factors for survival outcomes associated with LLR for CRLM., Methods: A single-center retrospective analysis of a prospectively maintained database was performed. The inclusion period ranged from September 2011 until mid-March 2020., Results: Two hundred consecutive LLRs were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates equalled 54.8% and 49%, respectively. A pushing (HR = 5.42, 95% CI 1.56-18.88, p = 0.008), as well as a replacement (3.87, 1.05-14.2, p = 0.04) growth pattern of the CRLM, poor differentiation of the primary colorectal cancer (CRC) (3.72, 1.72-8.07, p < 0.001) and administration of neoadjuvant chemotherapy (NAC) (2.95, 1.28-6.8, p = 0.01) were identified as independent predictors of a worse OS. Requirement of more than 6 cycles of NAC (6.17, 2.37-16.03, p < 0.001), a replacement (4.96, 1.91-12.87, p < 0.001), as well as a pushing (4.3, 1.68-11, p = 0.002) growth pattern of the CRLM and poor differentiation of the primary CRC (2.61, 1.31-5.2, p = 0.006) were identified as independent predictors of a worse DFS., Conclusion: LLR for CRLM offers adequate long-term oncologic outcomes. OS and DFS rates are negatively affected by the administration of NAC and by pathological features, including the differentiation grade of the primary CRC and the histological growth pattern of the CRLM., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The presence of suitable carbon sources for enhanced biological phosphorus removal (EBPR) plays a key role in phosphorus removal from wastewater in urban WWTP. For wastewaters with low volatile fatty acids (VFAs) content, an external carbon addition is necessary. As methanol is the most commonly external carbon source used for denitrification it could be a priori a promising alternative, but previous attempts to use it for EBPR have failed. This study is the first successful report of methanol utilization as external carbon source for EBPR. Since a direct replacement strategy (i.e., supply of methanol as a sole carbon source to a propionic-fed PAO-enriched sludge) failed, a novel process was designed and implemented successfully: development of a consortium with anaerobic biomass and polyphosphate accumulating organisms (PAOs). Methanol-degrading acetogens were (i) selected against other anaerobic methanol degraders from an anaerobic sludge; (ii) subjected to conventional EBPR conditions (anaerobic + aerobic); and (iii) bioaugmented with PAOs. EBPR with methanol as a sole carbon source was sustained in a mid-term basis with this procedure., (Copyright © 2012 Wiley Periodicals, Inc.)

Nitric oxide (NO) activates soluble guanylate cyclase (sGC) to produce guanosine-3',5'-cyclic-monophosphate (cGMP). The aim of this study was to investigate the nitrergic regulation of jejunal motility in sGCalpha(1) knockout (KO) mice. Functional responses to nitrergic stimuli and cGMP levels in response to nitrergic stimuli were determined in circular muscle strips. Intestinal transit was determined. Nitrergic relaxations induced by electrical field stimulation and exogenous NO were almost abolished in male KO strips, but only minimally reduced and sensitive to ODQ in female KO strips. Basal cGMP levels were decreased in KO strips, but NO still induced an increase in cGMP levels. Transit was not attenuated in male nor female KO mice. In vitro, sGCalpha(1)beta(1) is the most important isoform in nitrergic relaxation of jejunum, but nitrergic relaxation can also occur via sGCalpha(2)beta(1) activation. The latter mechanism is more pronounced in female than in male KO mice. In vivo, no important implications on intestinal motility were observed in male and female KO mice.

Background: In animal models of postoperative ileus (POI), inflammation of the intestine plays an important role in the pathogenesis of POI. Changes in alpha(2)-adrenoceptors and nitrergic regulation have been proposed to be implicated. The aim of our study was to investigate the presynaptic alpha(2)-receptor-mediated control of cholinergic nerve activity, the nitrergic nerve activity, and the possible role of soluble guanylate cyclase (sGC) during the inflammatory phase of POI., Methods: Ileus was induced by anesthesia and manipulation of the rat jejunum. Rats were treated with the sGC inhibitors methylene blue or ODQ; nonoperated animals served as controls. After 24 h, plasma and jejunal tissue were collected for biochemical assays, nitric oxide synthase-1 (NOS-1)-immunohistochemistry, acetylcholine (Ach)-release experiments, and muscle tension experiments., Results: In all operated animal groups, myeloperoxidase activity was significantly increased, which indicates initiation of an inflammatory response. The alpha(2)-adrenoceptor agonist UK14,304 reduced electrically induced Ach-release similarly in operated and nonoperated animals. In strips of operated animals, electrically induced nitrergic relaxations were decreased, whereas relaxations induced by exogenous nitric oxide (NO) remained unchanged compared with control. The number of myenteric neurons and the percentage of NOS-1-positive neurons were not influenced. Plasmatic cyclic guanosine monophosphate (cGMP) levels were decreased in all operated groups, whereas jejunal cGMP levels were unchanged compared with nonoperated controls; treatment with sGC inhibitors did not reduce plasmatic cGMP levels., Conclusions: This study demonstrates that presynaptic alpha(2)-receptor mediated control of intestinal cholinergic nerve activity is unchanged during manipulation-induced inflammation. However, this inflammation induces impaired nitrergic neurotransmission related to decreased NOS-1 activity in the nitrergic nerves.

In distal colon, both nitric oxide (NO) and ATP are involved in non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission. The role of the soluble guanylate cyclase (sGC) isoforms alpha(1)beta(1) and alpha(2)beta(1), and of the small conductance Ca(2+)-dependent K(+) channels (SK(Ca) channels) in the relaxation of distal colon by exogenous NO and by NANC nerve stimulation was investigated, comparing wild type (WT) and sGCalpha(1) knockout (KO) mice. In WT strips, the relaxation induced by electrical field stimulation (EFS) at 1 Hz but not at 2-8 Hz was significantly reduced by the NO-synthase inhibitor L-NAME or the sGC inhibitor ODQ. In sGCalpha(1) KO strips, the EFS-induced relaxation at 1 Hz was significantly reduced and no longer influenced by L-NAME or ODQ. The SK(Ca) channel blocker apamin alone had no inhibitory effect on EFS-induced relaxation, but combined with ODQ or L-NAME, apamin inhibited the relaxation induced by EFS at 2-8 Hz in WT strips and at 8 Hz in sGCalpha(1) KO strips. Relaxation by exogenous NO was significantly attenuated in sGCalpha(1) KO strips, but could still be reduced further by ODQ. Basal cGMP levels were lower in sGCalpha(1) KO strips but NO still significantly increased cGMP levels versus basal. In conclusion, in the absence of sGCalpha(1)beta(1), exogenous NO is able to partially act through sGCalpha(2)beta(1). NO, acting via sGCalpha(1)beta(1), is the principal neurotransmitter in EFS-evoked responses at 1 Hz. At higher stimulation frequencies, NO, acting at sGCalpha(1)beta(1) and/or sGCalpha(2)beta(1), functions together with another transmitter, probably ATP acting via SK(Ca) channels, with some degree of redundancy.

The principal target of the relaxant neurotransmitter nitric oxide (NO) is soluble guanylate cyclase (sGC). As the alpha(1)beta(1)-isoform of sGC is the predominant one in the gastrointestinal tract, the aim of this study was to investigate the role of sGC in nitrergic regulation of gastric motility in male and female sGCalpha(1) knock-out (KO) mice. In circular gastric fundus muscle strips, functional responses and cGMP levels were determined in response to nitrergic and non-nitrergic stimuli. sGC subunit mRNA expression in fundus was measured by real-time RT-PCR; in vivo gastric emptying of a phenol red meal was determined. No changes were observed in sGC subunit mRNA levels between wild-type (WT) and KO tissues. Nitrergic relaxations induced by short trains of electrical field stimulation (EFS) were abolished, while those by long trains of EFS were reduced in KO strips; the latter responses were abolished by 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The relaxations evoked by exogenous NO and the NO-independent sGC activator BAY 41-2272 were reduced in KO strips but still sensitive to ODQ. Relaxations induced by vasoactive intestinal peptide (VIP) and 8-bromo-cGMP were not influenced. Basal cGMP levels were decreased in KO strips but NO, long train EFS and BAY 41-2272 still induced a moderate ODQ-sensitive increase in cGMP levels. Gastric emptying, measured at 15 and 60 min, was increased at 15 min in male KO mice. sGCalpha(1)beta(1) plays an important role in gastric nitrergic relaxation in vitro, but some degree of nitrergic relaxation can occur via sGCalpha(2)beta(1) activation in sGCalpha(1) KO mice, which contributes to the moderate in vivo consequence on gastric emptying.

1. Conflicting data have been reported on the contribution of nitric oxide (NO) to inhibitory neurotransmission in rat jejunum. Therefore, the mechanism of relaxation and contribution to inhibitory neurotransmission of NO, adenosine 5'-triphosphate (ATP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) was examined in the circular muscle of Wistar-Han rat jejunum. 2. Mucosa-free circular muscle strips were precontracted with methacholine in the presence of guanethidine and exposed to electrical field stimulation (EFS) and exogenous NO, ATP, VIP and PACAP. All stimuli induced reduction of tone and inhibition of phasic motility. Only electrically induced responses were sensitive to tetrodotoxin (3 x 10(-6) m). 3. NO (10(-6)-10(-4) m)-induced concentration-dependent relaxations that were inhibited by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ; 10(-5) m) and the small conductance Ca(2+)-activated K(+)-channel blocker apamin (APA; 3 x 10(-8) m). 4. Relaxations elicited by exogenous ATP (10(-4)-10(-3) m) were inhibited by the P2Y purinoceptor antagonist reactive blue 2 (RB2; 3 x 10(-4) m), but not by APA and ODQ. 5. The inhibitory responses evoked by 10(-7) m VIP and 3 x 10(-8) m PACAP were decreased by the selective PAC(1) receptor antagonist PACAP(6-38) (3 x 10(-6) m) and APA. The VPAC(2) receptor antagonist PG99-465 (3 x 10(-7) m) reduced relaxations caused by VIP, but not those by PACAP, while the VPAC(1) receptor antagonist PG97-269 (3 x 10(-7) m) had no influence. 6. EFS-induced relaxations were inhibited by the NO-synthase inhibitor N(omega)-nitro-l-arginine methyl ester (3 x 10(-4) m), ODQ and APA, but not by RB2, PG97-269, PG99-465 and PACAP(6-38). 7. These results suggest that NO is the main inhibitory neurotransmitter in the circular muscle of Wistar-Han rat jejunum acting through a rise in cyclic guanosine monophosphate levels and activation of small conductance Ca(2+)-dependent K(+) channels.

Several studies have tried to establish the prevalence of visual-perceptual impairment in children with physical disabilities, particularly in those with cerebral palsy (CP), but failed to take into account the selective impairment of non-verbal intelligence that is frequent in these children. This has resulted in the confounding of visual-perceptual and non-verbal intelligence impairment. In the present study we aimed to determine how widespread visual-perceptual impairment is in children with CP by evaluating perceptual ability together with the performance level on non-verbal intelligence subtests. All children (n=96; 44 females, 52 males) who attended an institute for children with physical disabilities were included (age ranged from 4 years 11 months to 21 years 5 months) who had a non-verbal mental age between 3 and 7 years; Total IQ was <85 in 91% of participants. They were given a grating acuity task and the visual-perceptual battery L94, comprising six visual object recognition and two visuoconstruction tasks. Relative to their performance level on non-verbal intelligence subtests, 37.5% of the children were impaired on at least one task, and 18.7% on two or more tasks. No child was impaired on the visuoconstruction tasks. Visual-perceptual impairment was highest among six children with brain malformation (67%), followed by spastic CP (40%), and brain damage acquired after the first year of life (38%). There was no difference in visual-perceptual impairment between the subtypes of spastic CP. Results are not secondary to visual acuity deficits, as only one L94 task was significantly correlated with acuity impairment. We conclude that visual-perceptual impairment is frequent in children with physical disabilities, and not restricted to children with CP of hypoxic-ischaemic origin.