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This paper proposes a new methodological pattern to assess the effectiveness of Order Review and Release (ORR) techniques in a job shop environment. The standpoint for this new method lies in the following remarks: (i) comparisons among ORR models should be performed in dynamic and uncertain environments; (ii) ORR techniques robustness toward the shop uncertainty and perturbations should be considered; and (iii) ORR models should be compared by changing their features one at a time, instead of comparing completely different ORR techniques. Consistently, we present a comparison among three ORR models, previously developed in literature, aimed at investigating: (i) the impact of a dynamic and uncertain environment on the performances achieved; (ii) the robustness of these ORR models when facing some environmental perturbations, like the system workload, the mix imbalance, the machine unavailability and the processing time variability, that usually take place in real life job shops; and (iii) the overall effectiveness of the way workload is accounted for over time, since the models differentiate only by this item, while any other feature of the release mechanism is the same. Simulation results highlight that the performances of the ORR techniques tested depend on how perturbed the environment where they are implemented is. Moreover, the ORR techniques tested greatly differ in their robustness against environment perturbations. [ABSTRACT FROM AUTHOR]

In many job shop environments production orders arrive continuously at the production system over time. If an 'order review and release' (ORR) technique is applied, the arrival itself does not necessarily involve the release of a job to the shop floor; in fact, the ORR activities determine which jobs have to be selectively dispatched to the shop floor and when job release is to take place, so as to improve job shop management and performances. This paper introduces a review and a classification framework of the main research work carried out to date. We have considered eight main dimensions that describe the fundamental principles, characteristics and logic of existing order review and release techniques. The classification of selected models from the specialised literature by means of the proposed framework provides a better understanding for the practitioners and, on the other hand, aims to indicate to researchers the most promising research paths. [ABSTRACT FROM AUTHOR]

Student activities and experimental procedures are described for an experiment using black and white photographic development to illustrate the determination of reaction rate, kinetic order of a reactant, and activation energy. (Author/SK)

OBJECTIVE:: A case of lumbosacral plexopathy (LSP) following operation for mesenteric thrombosis. DESIGN:: Case report of a 64-year-old man who developed weakness and numbness of the distal legs after an operation for mesenteric thrombosis. SETTING:: Department of Physical Medicine and Rehabilitation, University Hospital La Fe, Valencia, Spain. SUBJECT:: Single patient case report. MAIN OUTCOME MEASURE:: Clinical and electromyography follow-up of the patient between October 1996 and August 1997. RESULTS:: Physical examination revealed marked lower extremity weakness, hypotonia, hyporreflexia and normal bowel and bladder function. Electromyography demonstrated marked denervation of all major muscle groups, and sensory nerve conduction showed absence of responses in all peripheral nerves, in both legs. CONCLUSION:: To our knowledge, bilateral LSP following an intervention of mesenteric thrombosis, has never been reported in the literature. Diagnosis of LSP might be based on electromyography and nerve conduction studies that demonstrate electrodiagnostic criteria for LSP, including denervation in muscles innervated by at least two lumbosacral segmental levels and involving at least two different peripheral nerves, without paraspinal involvement. [ABSTRACT FROM AUTHOR]

Load-oriented manufacturing control (LOMC), a well known probabilistic approach to workload control, is based on limiting and smoothing workload using one static parameter for each workcentre, called load limit (LL). The value of this parameter is set by the shop managers based on the planned lead time at each workcentre. In this paper the use of LL is shown to be inappropriate for the smoothing of workloads when the workload is not sufficiently balanced. We propose to enhance the LOMC model by introducing two sets of parameters: [ABSTRACT FROM AUTHOR]

The present study analyzed different protocols of administration of boronophenylalanine (BPA) and sodium butyrate (NaB) to increase the BNCT efficacy for poorly differentiated thyroid cancer (PDTC). Nude mice implanted with human PDTC cells (WRO) were distributed into four protocols: 1) BPA; 2) BPA + ip NaB; 3) BPA + oral NaB; 4) Control. Biodistribution and histologic studies were performed. LAT (BPA transporter) isoforms gene expression was assessed by RT-PCR. Tumor growth delay was observed in animals of the Protocol #3 (p < 0.05). NaB (Protocol #2) increased tumor boron uptake 2-h post BPA injection (p < 0.05). On the other hand, NaB upregulated the expression of all the isoforms of the LAT transporter in vitro. Histologic studies showed a significant decrease of mitotic activity and an increase of vacuoles in tumors of Protocol #3. Neutrons alone or combined with NaB caused some tumor growth delay (p < 0.05), while in the BNCT and BNCT + NaB groups, there was a halt in tumor growth in 70 and 80% of the animals, respectively. Intraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results. • Sodium butyrate (NaB), a histone deacetylase inhibitor, has antitumoral properties. • Different protocols of combined administration of NaB and BPA were studied. • Combination of NaB with BPA could improve the outcome of BNCT in an in vivo experimental model of PDTC. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between first and second trimester marker for the screening of Down's syndrome in Great Britain. Screening was done to women at the age of 27 to 35 with the usual triple test and the measurement of nuchal translucency (NT) used. The result showed that in first trimester, NT resulted in a positive rate of 7.03% while the triple test in the second trimester gave a positive rate of 7.7%.

For patients experiencing acute coronary syndrome, early symptom recognition is paramount; this is challenging without chest pain presentation. The aims of this scoping review were to collate definitions, proportions, symptoms, risk factors and outcomes for presentations without cardiac chest pain. Full-text peer reviewed articles covering acute coronary syndrome symptoms without cardiac chest pain were included. MEDLINE, CINAHL, Scopus and Embase were systematically searched from 2000 to April 2023 with adult and English limiters; 41 articles were selected from 2,954. Dyspnoea was the most reported (n=39) and most prevalent symptom (11.6-72%). Neurological symptoms, fatigue/weakness, nausea/ vomiting, atypical chest pain and diaphoresis were also common. Advancing age appeared independently associated with presentations without cardiac chest pain; however, findings were mixed regarding other risk factors (sex and diabetes). Patients without cardiac chest pain had worse outcomes: increased mortality, morbidity, greater prehospital and intervention delays and suboptimal use of guideline driven care. There is a need for structured data collection, analysis and interpretation., Competing Interests: Disclosure: AC has received a future fellowship grant from the Australian Research Council; PO has received consulting fees from The Paramedic Foundation and the Australian Health Professional Regulatory; is on the boards of The Paramedic Network, the American Paramedic Association and the Australasian College of Paramedicine Community Paramedic Working Party; and is director of the Global Paramedic Higher Education Council. All other authors have no conflicts of interest to declare. Authors’ contributions: Conceptualisation: MP and MAR; data curation: MP; formal analysis: MP, AC and MAR; funding acquisition: not applicable; investigation: MP and CT; methodology: MP and MAR; project administration: MP; resources: MP; software: not applicable; supervision: AC and MAR; validation: MP, AC and MAR; visualisation: MP; writing – original draft preparation: MP; writing – review & editing: MP, AC, CT, PO and MAR., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

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 < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001)., Conclusion: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications., Trial Registration: ClinicalTrials.gov identifier: NCT02328131., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Background: Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that 2-IHDA inhibits several thyroid parameters and it has been postulated as intermediary on the action of iodide function., Objective: To explore different mechanisms involved during the involution of the hyperplastic thyroid gland of Wistar rats towards normality induced by 2-IHDA., Methods: Goiter was induced by the administration of MMI for 10 days, then the treatment was discontinued and Wistar rats were injected with 2-IHDA or KI., Results: During involution, 2-IHDA treatment reduced PCNA expression compared to spontaneous involution. KI treatment caused an increase of Caspase-3 activity and TUNEL-positive cells. In contrast, 2-IHDA failed to alter this value but induced an increase of LC3B expression. KI but not 2-IHDA led to an increase in peroxides levels, catalase and glutathione peroxidase activity., Conclusions: We demonstrated that 2-IHDA, in contrast to iodide, did not lead to an increase in oxidative stress or apoptosis induction, indicating that the involution triggered by 2-IHDA in Wistar rats, is primarily due to the inhibition of cell proliferation and the induction of autophagy., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Published by Elsevier Inc.)

Background: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication., Aim: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg)., Methods: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022., Results: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness., Conclusions: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Introduction: Iodide is an essential micronutrient for the synthesis of thyroid hormones and its imbalance is involved in the origin of different thyroid pathological processes. Selenium (Se) is another essential trace element that contributes to thyroid preservation through the control of the redox homeostasis. Different studies have demonstrated that sodium-iodide-symporter (NIS) is downregulated in the presence of iodide excess and Se supplementation reverses this effect. We also demonstrated that NOX4-derived ROS are involved in NIS repression induced by iodide excess. The aim of this study was to investigate how Se bioavailability is decisive in the sensitivity to iodide excess on a differentiated rat thyroid cell line (FRTL-5)., Results: We demonstrated that siRNA-mediated silencing of Nox4 suppressed AKT phosphorylation induced by iodide excess. Iodide increases TGF-β1 mRNA expression, AKT phosphorylation, ROS levels and decreases GPX1 and TXRND1 mRNAs expression while Se reversed these effects. Furthermore, iodide induced Nrf2 transcriptional activity only in Se-supplemented cultures, suggesting that Se positively influences Nrf2 activation and selenoenzyme response in FRTL-5. Se, also inhibited NF-κB phosphorylation induced by iodide excess. In addition, we found that iodide excess decreased total phosphatase activity and PTP1B and PTEN mRNA expression. Se supply restored only PTEN mRNA expression. Finally, we studied the 2-α-iodohexadecanal (2-IHD) effects since it has been proposed as intermediary of iodide action on thyroid autoregulation. 2-IHD stimulated PI3K/AKT activity and reduced NIS expression by a ROS-independent mechanism. Also, we found that 2-IHD increased TGF-β1 mRNA and TGF-β inhibitor (SB431542) reverses the 2-IHD inhibitory effect on NIS mRNA expression, suggesting that TGF-β1 signaling pathway could be involved. Although Se reduced 2-IHD-induced TGFB1 levels, it could not reverse its inhibitory effect on NIS expression., Conclusion: Our study suggests that Se bioavailability may improve the expression of antioxidant genes through the activation of Nrf2, interfere in PI3K/AKT signaling and NIS expression by redox modulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain., Aim: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg)., Methods: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection., Results: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection., Conclusions: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety., Competing Interests: Competing interests: XC has received research grants and fees for lectures from Allergan. JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly Spindler, Allergan, Diasorin, Gebro Pharma and Richen. OPN received research funding from Allergan and Mayoly Spindler. Dr Bordin served as a lecturer for Astellas, AstraZeneca, KRKA, and Abbott. FM is a consultant for PHATHOM and DaVoltera and has received grants from Allergan, bioMerieux and Mobidiag. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The synergy of superparamagnetic iron oxide nanoparticles (SPIONs) and ionizing radiation (IR), attributed to reactive oxygen species (ROS) and DNA double-strand breaks (DSBs) increase, was widely investigated in different cancers, but scarcely in melanoma. Herein, SPIONs were evaluated as radiosensitizers in A-375 human melanoma cells. Moreover, the effect of the combined treatment of SPIONs and gamma irradiation (SPIONs-IR) was assessed at the DNA level, where DSBs induction and their repair capacity were studied. SPIONs were synthesized, stabilized by poly(ethylene glycol) methyl ether and physicochemically characterized by high resolution-transmission electron microscopy (HR-TEM), X-ray diffraction and magnetometry and dynamic light scattering. The obtained nanoparticles showing superparamagnetic behavior and low dispersion in shape and sizes were tested in A-375 cells. The intracellular internalization of SPIONs was verified by HR-TEM and quantified by inductively coupled plasma atomic emission spectroscopy. Cells treated with SPIONs exhibited high ROS levels without associated cytotoxicity. Next, a significant radiosensitization in SPIONs-IR vs. control (IR) cells was demonstrated at 1 Gy of gamma radiation. Furthermore, a decreased DSBs repair capacity in SPIONs-IR vs. IR-treated cells was evidenced by the size increase of persistent phosphorylated H2AX foci at 24 h post-irradiation. In conclusion, these nanoparticles show the potential to radiosensitize melanoma cells by the induction of unrepairable DNA damage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Central venous catheter (CVC) placement is a routine procedure but is potentially associated with severe complications. Relatively small studies investigated if the use of ultrasound is effective in bridging the skill gap between proficient and not proficient operators, while patient safety during training remains a controversial topic. The first aim of this study was to evaluate if resident proficiency affects the failure rate in CVC positioning under ultrasound guidance. In addition, it aimed to investigate the different rate of complications between proficient and non proficient residents., Methods: We conducted a cohort study including CVC placed by residents at the University Hospital of Padova, from November 1, 2012 to July 9, 2020 comparing proficient and non proficient residents. To avoid bias the two cohorts were matched using propensity score., Results: A total of 356 residents positioned 2310 CVC during the 8 year study period. Among them, two groups of 1060 CVCs each were matched with a propensity score analysis. There was no difference in the failure rate among the groups (2.8 vs 2.7%, p-value 0.895). Moreover, cohorts had the same rate of hematomas, catheter tip malposition, arterial puncture and pneumothorax. No cases of hemothorax were reported., Conclusions: We found the same rate of success and incidence of adverse complications among cohorts, meaning that the process of skill acquisition is safe as long as appropriate training and direct supervision by a senior consultant are available., (© 2021. The Author(s).)

Background: We present the first case of a patient with obstructive sleep apnea syndrome (OSA), where drug induced sleep endoscopy was helpful to suspect a non-acid reflux disease and showed an improvement in a swollen epiglottis after treatment. Patient ameliorated significantly his disease only with medical therapy., Case Presentation: A 54-year-old man without significant anatomical findings with obstructive sleep apnea syndrome and non-acid gastroesophageal reflux disease (GERD) disease whose Apnea- hypopnea index (AHI) was significantly reduced with the intake of 500 mg of sodium alginate twice a day for 6 months. Conventional digestive tests such as esophagoscopy and simple- and double-channel 24-h pH-metry suggested mild GERD. Conventional proton-pump inhibitor treatment with pantoprazole (40 mg daily) was started without any improvement in his sleep. Multichannel intraluminal 24-h impedanciometry indicated the presence of severe pathological GER of gaseous origin. The patient's AHI decreased from 25.3 at baseline to 8 after treatment with sodium alginate. A drug-induced sleep endoscopy study showed the changes before and after this treatment and was helpful for the diagnosis., Conclusions: Thus, medical treatment can be a therapeutic option in some patients with OSA. Multichannel 24-h impedanciometry should be performed when nonacid GERD is suspected.

Introduction: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management.", Methods: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control., Results: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs. Longer treatment durations were significantly associated with a higher incidence of AEs in standard triple, concomitant, bismuth quadruple, and levofloxacin triple or quadruple therapies., Discussion: Helicobacter pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Their appearance does not interfere significantly with treatment compliance., Competing Interests: The remaining list of authors, their affiliations, contributions and conflicts of interests are listed in Supplementary file 1. Contribution Log, available online at http://links.lww.com/AJG/B961., (Copyright © 2021 by The American College of Gastroenterology.)

Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation., Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy., Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line., Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases., Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain.

About 95 % of people diagnosed with glioblastoma die within five years. Glioblastoma is the most aggressive central nervous system tumour. It is necessary to make progress in the glioblastoma treatment so that advanced chemotherapy drugs or radiation therapy or, ideally, two-in-one hybrid systems should be implemented. Tyrosine kinase receptors-inhibitors and boron neutron capture therapy (BNCT), together, could provide a therapeutic strategy. In this work, sunitinib decorated-carborane hybrids were prepared and biologically evaluated identifying excellent antitumoral- and BNCT-agents. One of the selected hybrids was studied against glioma-cells and found to be 4 times more cytotoxic than sunitinib and 1.7 times more effective than 10 B-boronophenylalanine fructose complex when the cells were irradiated with neutrons., (© 2020 Wiley-VCH GmbH.)

Pre-mRNA splicing is a very dynamic process that involves many molecular rearrangements of the spliceosome subcomplexes during assembly, RNA processing, and release of the complex components. Glycerol gradient centrifugation has been used for the separation of protein or RNP (RiboNucleoProtein) complexes for functional and structural studies. Here, we describe the utilization of Grafix (Gradient Fixation), which was first developed to purify and stabilize macromolecular complexes for single particle cryo-electron microscopy, to identify interactions between splicing factors that bind transiently to the spliceosome complex. This method is based on the centrifugation of samples into an increasing concentration of a fixation reagent to stabilize complexes. After centrifugation of yeast total extracts loaded on glycerol gradients, recovered fractions are analyzed by dot blot for the identification of the spliceosome sub-complexes and determination of the presence of individual splicing factors.

Background: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin., Aim: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline., Methods: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed., Results: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29)., Conclusion: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended., (© 2020 John Wiley & Sons Ltd.)

Background: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended., Aim: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg)., Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019., Results: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera ® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases., Conclusion: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results., (© 2020 John Wiley & Sons Ltd.)

Research question: Urine LH testing may be useful to confirm an LH surge after the GnRH agonist (GnRHa) trigger prior to oocyte retrieval in IVF. Design: A prospective cohort study, including oocyte donors undergoing ovarian stimulation, treated with a GnRHa trigger for final oocyte maturation. Urine LH testing was performed at home, 12 h after the GnRHa trigger. In the case of a negative result, serum LH and progesterone measurements were done that same day. Donors with no serum LH peak after trigger were re-scheduled using a dual trigger, with GnRHa and hCG. Results: Three hundred and fifty nine oocyte donors were included in the analysis. Three hundred and fifty six donors had positive urine LH tests, followed by oocyte retrieval. In one case, the LH test was positive, however, no oocytes were retrieved (false positive 1/356). Three LH tests were negative in urine: in one of these three cases, LH was tested again in blood, confirming an LH rise, consistent with an optimal response to the GnRHa trigger; in the other two cases, serum LH was <15 mUI/mL, after which the oocyte retrieval was re-scheduled for 36 h after an being re-triggered, resulting in the retrieval of 19 and 22 MII oocytes, respectively. Considering the cost analysis, it would be a significantly cost-saving strategy, as blood testing would have costed 14,840€ vs. only 185.5€ in urine LH kits. Conclusions: Urinary testing of the LH surge after GnRHa trigger is easy, safe, reliable, and convenient. In addition, LH urine testing allows identifying donors and patients who could benefit from a rescue hCG trigger after an unsuccessful GnRHa trigger., (Copyright © 2020 Cozzolino, Matey, Alvarez, Toribio, López, Perona, Henzenn, Piró, Humaidan and Garcia-Velasco.)

Mesial temporal lobe epilepsy with hippocampal sclerosis represents the most common epilepsy syndrome in adult patients with medically intractable partial epilepsy. Mesial temporal lobe epilepsy is usually regarded as a polygenic and complex disorder, still poorly understood but probably caused and perpetuated by dysregulation of numerous biological networks and cellular functions. The study of gene expression changes by single nucleotide polymorphisms in regulatory elements (expression quantitative trait loci, eQTLs) has been shown to be a powerful complementary approach to the detection and understanding of risk loci by genome-wide association studies. We performed a whole (gene and exon-level) transcriptome analysis on cortical tissue samples (Brodmann areas 20 and 21) from 86 patients with mesial temporal lobe epilepsy with hippocampal sclerosis and 75 neurologically healthy controls. Genome-wide genotyping data from the same individuals (patients and controls) were analysed and paired with the transcriptome data. We report potential epilepsy-risk eQTLs, some of which are specific to tissue from patients with mesial temporal lobe epilepsy with hippocampal sclerosis. We also found large transcriptional and splicing deregulation in mesial temporal lobe epilepsy with hippocampal sclerosis tissue as well as gene networks involving neuronal and glial mechanisms that provide new insights into the cause and maintenance of the seizures. These data (available via the 'Seizubraineac' web-tool resource, www.seizubraineac.org) will facilitate the identification of new therapeutic targets and biomarkers as well as genetic risk variants that could influence epilepsy and pharmacoresistance., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups., Aims: We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE., Methods: In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34)., Results: mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients., Conclusions: Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE., (© 2018 John Wiley & Sons Ltd.)

Radiotherapy is one of the leading treatments for clinical cancer therapy. External beam radiotherapy has been proposed as an adjuvant treatment for patients bearing differentiated thyroid cancer refractory to conventional therapy. Our purpose was to study the combined effect of HDAC inhibitors (HDACi) and ionizing irradiation in thyroid cancer cell lines (Nthy-ori 3-1, WRO, TPC-1 and 8505c). HDACi radiosensitized thyroid cancer cells as evidenced by the reduction of survival fraction, whereas they had no effect in the normal cells. HDACi enhanced radiation-induced cell death in WRO cells. Gamma-H2AX foci number increased and persisted long after ionizing exposure in the HDACi-treated cells (WRO and TPC-1). Moreover, the expression of the repair-related gene Ku80 was differentially modulated only in the cancer cells, by the compounds at the protein and/or mRNA levels. We present in vitro evidence that HDACi can enhance the radiosensitivity of human thyroid cancer cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of thyroid parameters such as thyroid proliferation and function. Several iodinated lipids, biosynthesized by the thyroid, were postulated as intermediaries in the action of iodide. Among these, iodolactone (IL-δ) and 2-iodohexadecanal (2-IHDA) have shown to inhibit several thyroid parameters. The antiproliferative effect of IL-δ is not restricted to the thyroid gland. IL-δ exhibits anti-tumor properties in breast cancer, neuroblastoma, glioblastoma, melanoma and lung carcinoma cells suggesting that IL-δ could be used as a chemotherapeutic agent. Moreover in a colon cancer cell line (HT-29), IL-δ induced cell death, and this effect was mediated by reactive oxygen species (ROS) generation. The aim of the present study was to analyze the sources of reactive oxygen species induced by IL-δ and to explore the contribution of ROS induced by IL-δ on cell proliferation and apoptosis., Methodology and Results: Cancer thyroid follicular (WRO) and papilar (TPC-1) cells lines were treated with IL-δ. Proliferation and apoptosis was analyzed. IL-δ caused a significant loss of cell viability on WRO and TPC-1 cells in a concentration dependent manner and induced apoptosis after 3 h of treatment. Furthermore, IL-δ (10 μM) increased ROS production (39% WRO and 20% TPC-1). The concomitant treatment of WRO and TPC-1 cells with Trolox or NAC plus IL-δ abrogated the augment of ROS induced by IL-δ exposure. Additionally Trolox and NAC reversed the effect of IL-δ on cell proliferation and apoptosis. Only in WRO cells IL-δ upregulates NADPH oxidase NOX4 expression, and siRNA targeted knock-down of NOX4 attenuates ROS production, apoptosis (p < 0.05) and the inhibitory effect of IL-δ on cell proliferation and PCNA expression (p < 0.05)., Conclusions: The antiproliferative and pro-apoptotic effect of IL-δ is mediated by different mechanisms and pathway involving different sources of ROS generation depending on the cellular context., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Rising trends in eosinophilic esophagitis (EoE) have been repeatedly linked to declining Helicobacter pylori (H. pylori) infection, mostly in retrospective studies. We aimed to prospectively evaluate this inverse association., Methods: Prospective case-control study conducted in 23 centers. Children and adults naïve to eradication therapy for H. pylori were included. Cases were EoE patients, whereas controls were defined by esophageal symptoms and <5 eos/HPF on esophageal biopsies. H. pylori status was diagnosed by non-invasive (excluding serology) or invasive testing off proton pump inhibitor (PPI) therapy for 2 weeks. Atopy was defined by the presence of IgE-mediated conditions diagnosed by an allergist., Results: 808 individuals, including 404 cases and 404 controls (170 children) were enrolled. Overall H. pylori prevalence was 38% (45% children vs. 37% adults, p 0.009) and was not different between cases and controls (37% vs. 40%, p 0.3; odds ratio (OR) 0.97; 95% confidence interval (CI) 0.73-1.30), neither in children (42% vs. 46%, p 0.1) nor in adults (36% vs. 38%, p 0.4). Atopy (OR 0.85; 95%CI 0.75-0.98) and allergic rhinitis (OR 0.81; 95%CI 0.68-0.98) showed a borderline inverse association with H. pylori infection in EoE patients. This trend was not confirmed for asthma or food allergy., Conclusions: H. pylori infection was not inversely associated with EoE, neither in children nor in adults. A borderline inverse association was confirmed for atopy and allergic rhinitis, but not asthma of food allergy. Our findings question a true protective role of H. pylori infection against allergic disorders, including EoE.

Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis., Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples., Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit)., Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)