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  1. Nadzirin IB, Fortuny-Gomez A, Ngum N, Richards D, Ali S, Searcey M, et al.
    Br J Pharmacol, 2021 Dec;178(24):4859-4872.
    PMID: 34398973 DOI: 10.1111/bph.15663
    BACKGROUND AND PURPOSE: P2X4 is a ligand-gated cation channel activated by extracellular ATP involved in neuropathic pain, inflammation and arterial tone.

    EXPERIMENTAL APPROACH: Natural products were screened against human or mouse P2X4 activity using fura-2 loaded 1321N1 cells for measurement of intracellular Ca2+ responses. Whole-cell currents were measured by patch clamp. Human primary macrophage chemokine release was used to assess effect of taspine on inflammatory cell function. An enzymatic assay was performed to assess the effect of taspine on recombinant PI3-kinase.

    KEY RESULTS: A natural product screen identified taspine as an inhibitor of human P2X4 activity. Taspine inhibits human and mouse P2X4-mediated Ca2+ influx in 1321N1 cells expressing receptors but lacked activity at human P2X2, P2X3, P2X2/3 and P2X7 receptors. Taspine inhibited the maximal response at human and mouse P2X4 but effective on ATP potency. Taspine has a slow onset rate (~15 min for half-maximal inhibition), irreversible over 30 min of washout. Taspine inhibits P2X4-mediated Ca2+ signalling in mouse BV-2 microglia cells and human primary macrophage. Taspine inhibited P2X4-mediated CXCL5 secretion in human primary macrophage. Taspine reversed ivermectin-induced potentiation of P2X4 currents in 1321N1 stably expressing cells. The PI3-kinase inhibitor LY294002 mimicked the properties of taspine on P2X4-mediated Ca2+ influx and whole-cell currents. Taspine directly inhibited the enzymatic activity of recombinant PI3-kinase in a competitive manner.

    CONCLUSION AND IMPLICATIONS: Taspine is a novel natural product P2X4 receptor inhibitor, mediating its effect through PI3-kinase inhibition rather than receptor antagonism. Taspine can inhibit the pro-inflammatory signalling by P2X4 in human primary macrophage.

  2. James V, Samuel J, Kee CY, Ong GY
    Ultrasound J, 2020 Dec 03;12(1):51.
    PMID: 33270182 DOI: 10.1186/s13089-020-00199-y
    BACKGROUND: The presence of intra-abdominal calcification in the pediatric population can be due to a wide range of conditions. Calcification in the abdomen can be seen in normal or abnormal anatomical structures. In some patients, abnormal calcification points towards the pathology; whereas in others, calcification itself is the pathology. After a thorough history and clinical examination, point-of-care ultrasound (POCUS) would complement the assessment of acute abdominal pain, based on the list of differentials generated as per the abdominal region. The main objective of this article is to review commonly encountered causes of intra-abdominal calcifications in the pediatric population and help in clinical decision-making in a Pediatric Emergency Department.

    CASE PRESENTATION: We describe a series of pediatric patients who presented to the Pediatric Emergency Department with acute abdominal pain, in whom point-of-care ultrasound helped expedite the diagnosis by identifying varying types of calcification and associated sonological findings. For children who present to the Pediatric Emergency Department with significant abdominal pain, a rapid distinction between emergencies and non-emergencies is vital to decrease morbidity and mortality.

    CONCLUSIONS: In a child presenting to the Pediatric Emergency Department with abdominal pain, POCUS and the findings of calcifications can narrow or expand the differential diagnosis when integrated with history and physical exam, to a specific anatomic structure. Integrating these findings with additional sonological findings of an underlying pathology might raise sufficient concerns in the emergency physicians to warrant further investigations for the patient in the form of a formal radiological ultrasound and assist in the patient's early disposition. The use of POCUS might also help to categorize the type of calcification to one of the four main categories of intra-abdominal calcifications, namely concretions, conduit wall calcification, cyst wall calcification, and solid mass-type calcification. POCUS used thoughtfully can give a diagnosis and expand differential diagnosis, reduce cognitive bias, and reduce physician mental load. By integrating the use of POCUS with the history and clinical findings, it will be possible to expedite the management in children who present to the Pediatric Emergency Department with acute abdominal pain.

  3. Besser K, Malyon GP, Eborall WS, Paro da Cunha G, Filgueiras JG, Dowle A, et al.
    Nat Commun, 2018 12 03;9(1):5125.
    PMID: 30510200 DOI: 10.1038/s41467-018-07575-2
    Woody (lignocellulosic) plant biomass is an abundant renewable feedstock, rich in polysaccharides that are bound into an insoluble fiber composite with lignin. Marine crustacean woodborers of the genus Limnoria are among the few animals that can survive on a diet of this recalcitrant material without relying on gut resident microbiota. Analysis of fecal pellets revealed that Limnoria targets hexose-containing polysaccharides (mainly cellulose, and also glucomannans), corresponding with the abundance of cellulases in their digestive system, but xylans and lignin are largely unconsumed. We show that the limnoriid respiratory protein, hemocyanin, is abundant in the hindgut where wood is digested, that incubation of wood with hemocyanin markedly enhances its digestibility by cellulases, and that it modifies lignin. We propose that this activity of hemocyanins is instrumental to the ability of Limnoria to feed on wood in the absence of gut symbionts. These findings may hold potential for innovations in lignocellulose biorefining.
  4. Nyssen OP, Pratesi P, Spínola MA, Jonaitis L, Pérez-Aísa Á, Vaira D, et al.
    Antibiotics (Basel), 2023 Sep 10;12(9).
    PMID: 37760723 DOI: 10.3390/antibiotics12091427
    The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.
  5. Jonaitis P, Nyssen OP, Saracino IM, Fiorini G, Vaira D, Pérez-Aísa Á, et al.
    Sci Rep, 2023 Oct 11;13(1):17235.
    PMID: 37821503 DOI: 10.1038/s41598-023-43287-4
    The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p 
  6. Martínez-Domínguez SJ, Nyssen OP, Lanas Á, Alfaro E, Jonaitis L, Mahmudov U, et al.
    Helicobacter, 2024;29(4):e13111.
    PMID: 39001621 DOI: 10.1111/hel.13111
    BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance.

    METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis.

    RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p 

  7. Huguet JM, Ferrer-Barceló L, Suárez P, Barcelo-Cerda S, Sempere J, Saracino IM, et al.
    United European Gastroenterol J, 2024 Jul;12(6):691-704.
    PMID: 38685613 DOI: 10.1002/ueg2.12569
    BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy.

    OBJECTIVE: To determine which factors influence compliance with treatment.

    METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance.

    RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p 

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