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Background and study aims  The prevalence of digestive diseases seems to be high in African countries. Nonetheless, the human and material resources are scarce. The aim of the Portuguese volunteering project described in this report was to develop the specialty of digestive endoscopy in Sao Tome and Principe, a lower-middle-income country in Africa. Methods  Beginning by assessing the local needs and available resources and managing immediate issues related to this field, we aimed to provide the tools necessary to improve gastroenterological and endoscopic care in the country. The first step included training of the local teams, through the development and accomplishment of an adapted curriculum for a 3-year medical gastroenterological fellowship and a short-term nursing fellowship, both in Portugal, and the organization of regular gastroenterological and endoscopic theoretical and practical sessions in Sao Tome and Principe. Second, the endoscopy facilities of the unit were significantly optimized. Third, a web platform was designed to provide telemedicine incorporating real-time endoscopic imaging available remotely. Results  Through these sequential steps achieved in collaboration with Portuguese and local teams, this 5-year project provided the basis for gastroenterology care in this country. Conclusions  At the present time, Sao Tome and Principe has an autonomous, efficient and skilled team and unit to provide care for patients with gastrointestinal diseases who need endoscopic procedures., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Phosphatidic acid (PA) is a signaling lipid involved in the modulation of synaptic structure and functioning. Based on previous work showing a decreasing PA gradient along the longitudinal axis of the rodent hippocampus, we asked whether the dorsal hippocampus (DH) and the ventral hippocampus (VH) are differentially affected by PA modulation. Here, we show that phospholipase D1 (PLD1) is a major hippocampal PA source, compared to PLD2, and that PLD1 ablation affects predominantly the lipidome of the DH. Moreover, Pld1 knockout (KO) mice show specific deficits in novel object recognition and social interaction and disruption in the DH-VH dendritic arborization differentiation in CA1/CA3 pyramidal neurons. Also, Pld1 KO animals present reduced long-term depression (LTD) induction and reduced GluN2A and SNAP-25 protein levels in the DH. Overall, we observe that PLD1-derived PA reduction leads to differential lipid signatures along the longitudinal hippocampal axis, predominantly affecting DH organization and functioning., Competing Interests: Declaration of Interests G.D.P. is a full-time employee of Denali Therapeutics. G.D.P. and T.G.O. are listed as inventors on the patent number WO2010138869A1, “Modulation of Phospholipase D for the Treatment of Neurodegenerative Disorders.” R.B.C., G.D.P., and T.G.O. are listed as inventors on the patent number US20120302604A1, “Modulation of Phospholipase D for the Treatment of the Acute and Chronic Effects of Ethanol.”, (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although the hippocampus is known to be important for declarative memory, it is less clear how hippocampal output regulates motivated behaviours, such as social aggression. Here we report that pyramidal neurons in the CA2 region of the hippocampus, which are important for social memory, promote social aggression in mice. This action depends on output from CA2 to the lateral septum, which is selectively enhanced immediately before an attack. Activation of the lateral septum by CA2 recruits a circuit that disinhibits a subnucleus of the ventromedial hypothalamus that is known to trigger attack. The social hormone arginine vasopressin enhances social aggression by acting on arginine vasopressin 1b receptors on CA2 presynaptic terminals in the lateral septum to facilitate excitatory synaptic transmission. In this manner, release of arginine vasopressin in the lateral septum, driven by an animal's internal state, may serve as a modulatory control that determines whether CA2 activity leads to declarative memory of a social encounter and/or promotes motivated social aggression.

Emerging studies implicate Tau as an essential mediator of neuronal atrophy and cognitive impairment in Alzheimer's disease (AD), yet the factors that precipitate Tau dysfunction in AD are poorly understood. Chronic environmental stress and elevated glucocorticoids (GC), the major stress hormones, are associated with increased risk of AD and have been shown to trigger intracellular Tau accumulation and downstream Tau-dependent neuronal dysfunction. However, the mechanisms through which stress and GC disrupt Tau clearance and degradation in neurons remain unclear. Here, we demonstrate that Tau undergoes degradation via endolysosomal sorting in a pathway requiring the small GTPase Rab35 and the endosomal sorting complex required for transport (ESCRT) machinery. Furthermore, we find that GC impair Tau degradation by decreasing Rab35 levels, and that AAV-mediated expression of Rab35 in the hippocampus rescues GC-induced Tau accumulation and related neurostructural deficits. These studies indicate that the Rab35/ESCRT pathway is essential for Tau clearance and part of the mechanism through which GC precipitate brain pathology., (© 2018 The Authors.)

Recent results suggest that social memory requires the dorsal hippocampal CA2 region as well as a subset of ventral CA1 neurons. However, it is unclear whether dorsal CA2 and ventral CA1 represent parallel or sequential circuits. Moreover, because evidence implicating CA2 in social memory comes largely from long-term inactivation experiments, the dynamic role of CA2 in social memory remains unclear. Here, we use pharmacogenetics and optogenetics in mice to acutely and reversibly silence dorsal CA2 and its projections to ventral hippocampus. We show that dorsal CA2 activity is critical for encoding, consolidation, and recall phases of social memory. Moreover, dorsal CA2 contributes to social memory by providing strong excitatory input to the same subregion of ventral CA1 that contains the subset of neurons implicated in social memory. Thus, our studies provide new insights into a dorsal CA2 to ventral CA1 circuit whose dynamic activity is necessary for social memory.

Background: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective., Methods: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit., Results: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman's rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791-0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g., Conclusions: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX., Competing Interests: Conflict of interest statement: FM served as speaker and received honoraria from Merck Sharp & Dohme (NJ, USA), Abbvie (IL, USA), Vifor (Glattbrugg, Switzerland), Falk (USA), Laboratorios Vitoria (Amadora, Portugal), Ferring (Saint-Prex, Switzerland), Hospira (IL, USA) and Biogen (MA, USA).

Input-timing-dependent plasticity (ITDP) is a circuit-based synaptic learning rule by which paired activation of entorhinal cortical (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of SC excitation. We now find that paired stimulation of EC and SC inputs also induces ITDP of SC excitation of CA2 PNs. However, whereas CA1 ITDP results from long-term depression of feedforward inhibition (iLTD) as a result of activation of CB1 endocannabinoid receptors on cholecystokinin-expressing interneurons, CA2 ITDP results from iLTD through activation of δ-opioid receptors on parvalbumin-expressing interneurons. Furthermore, whereas CA1 ITDP has been previously linked to enhanced specificity of contextual memory, we find that CA2 ITDP is associated with enhanced social memory. Thus, ITDP may provide a general synaptic learning rule for distinct forms of hippocampal-dependent memory mediated by distinct hippocampal regions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62μg/mL vs. 1.15μg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3μg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250μg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays., Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs., Results: The three assays showed 81-96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 µg/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 µg/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 µg/ml. However, in samples with high levels of ADAs (>25 µg/ml) interference was only observed at IFX concentrations higher than 100 µg/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA- and IFX-/ADAs+ were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination., Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs-) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances., Competing Interests: The authors declare that there is no conflict of interest.

Background: Inflammatory Bowel Disease is known for its extra intestinal manifestations, the oral cavity is no exception., Objectives: The aim of this study was to evaluate the association between Inflammatory Bowel Disease and oral mucosa lesions and symptoms, and complementary to evaluate their possible relation with oral hygiene, smoking habits, drug therapy, duration and activity of the disease., Methods: Patients were selected from the Gastroenterology Clinic of a Portuguese tertiary referral hospital. This sample consisted of 113 patients previously diagnosed with ulcerative colitis or Crohn's disease along with a control group of 58 healthy individuals that were accompanying the study group patients to their appointments. Clinical interviews and clinical examinations were performed for data collection., Results: The patients in the study group were more affected by oral symptoms (P=0.011), and showed a trend towards a higher incidence of oral mucosal lesions, even though statistical significance was not reached (8.8% versus 3.4% in the control group; P=0.159). Patients in active phase were the most affected. No differences were detected between Crohn's disease and ulcerative colitis, or concerning smoking habits. The corticosteroid and immunosuppressant therapy seemed to increase the incidence of oral symptoms (P=0.052). The oral mucosa lesions increased and the oral symptoms decreased over the course of the disease, however without statistical significance., Conclusion: Oral mucosa's lesions and oral symptoms were positively associated with Inflammatory Bowel Disease, mainly during disease activity periods and conceivably, associated with corticosteroid and immunosuppressant therapy.

Head and neck cancer (HNC) patients tend to develop dysphagia. In order to preserve the nutritional support, many undergo endoscopic gastrostomy (PEG). In HNC patients, ostomy metastasis is considered a rare complication of PEG, but there are no reports of successful treatment of these metastatic cancers. We report the case of a 65 years old pharyngeal/laryngeal cancer patient who underwent a PEG before the neck surgery. He was considered to be cured, resumed oral intake and the PEG tube was removed. Ten months after, he returned with a metastasis at the ostomy site. A block resection of the stomach and abdominal wall was performed. Two years after the abdominal surgery, he is free of disease. Although usually considered a rare complication of the endoscopic gastrostomy, ostomy metastasis may be more frequent than usually considered and the present case report demonstrates that these patients may have a favourable outcome., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Context: Early refeeding after nonvariceal upper gastrointestinal bleeding is safe and reduces hospital stay/costs., Objectives: The aim of this study was obtaining objective data on refeeding after nonvariceal upper gastrointestinal bleeding., Methods: From 1 year span records of nonvariceal upper gastrointestinal bleeding patients that underwent urgent endoscopy: clinical features; rockall score; endoscopic data, including severity of lesions and therapy; feeding related records of seven days: liquid diet prescription, first liquid intake, soft/solid diet prescription, first soft/solid intake., Results: From 133 patients (84 men) Rockall classification was possible in 126: 76 score ≥5, 50 score <5. One persistent bleeding, eight rebled, two underwent surgery, 13 died. Ulcer was the major bleeding cause, 63 patients underwent endoscopic therapy. There was 142/532 possible refeeding records, no record 37% patients. Only 16% were fed during the first day and half were only fed on third day or later. Rockall <5 patients started oral diet sooner than Rockall ≥5. Patients that underwent endoscopic therapy were refed earlier than those without endotherapy., Conclusions: Most feeding records are missing. Data reveals delayed refeeding, especially in patients with low-risk lesions who should have been fed immediately. Nonvariceal upper gastrointestinal bleeding patients must be refed earlier, according to guidelines.

Context: Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy., Objective: To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels., Methods: We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1) before bowel cleaning, (2) before colonoscopy and (3) immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by "Sandwich" immunoassay. The statistical methods used were the paired t-test and ANOVA., Results: Thirty-seven patients (22M/15F) were included; age range 28-84 (mean 56 years). Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1), (2) and (3), respectively. An increase in value (2) compared with (1) was observed in 20/37 patients (P = 0.018), mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2) to (3) (P = 1.3x10-7)., Conclusions: A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.