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Objective: We describe the clinical presentation and ocular viral dynamics in patients with Monkeypox virus-related ophthalmic disease (MPXROD)., Methods: In this case series, we investigated five consecutive patients with confirmed mpox, diagnosed through a positive Monkeypox virus (MPXV) Polymerase Chain Reaction (PCR) test and presenting with ocular symptoms. They were referred from the Reference Center for Sexually Transmitted Infections in São Paulo (CRT) to the Uveitis Sector at the Federal University of São Paulo, between August and December 2022. We performed PCR testing on ocular samples and culture supernatants for MPXV in all patients. Viral sequencing was conducted in one of the cases., Results: Replicating MPXV was identified in at least one ocular sample of all patients, between day 31 and day 145 after the onset of skin lesions. All patients presented with keratitis, 3 with uveitis (60%) and two exhibited hypopyon (40%). The onset of ocular symptoms occurred at a mean of 21.2 days after the appearance of the first skin lesion and persisted, on average, for 61,.6 days, with a worsening trend observed until the initiation of tecovirimat treatment. Tecovirimat treatment was administered to all patients, with initiation occurring between 31 and 145 days after the onset of skin lesions. MPXV genome sequencing of an isolate from one patient classified it as belonging to lineage B1 in clade IIb., Conclusion: This study reveals a late onset and persistence of sight threatening ocular disease, along with potential viral infectivity even after systemic resolution in mpox cases. These findings highlight the risk of ongoing transmission from individuals with prolonged ocular manifestations, particularly through ocular discharge., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population., Methods: Retrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018)., Results: We evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD., Conclusion: We found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial., Competing Interests: Conflict of interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors., Methods: We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry. The assessed clinical outcomes were HCC development, liver transplantation, and death. Fine and Gray regression analysis stratified by centre was applied to determine the effects of individual covariates; the cumulative incidence of HCC was estimated using the competing risk method with death as a competing risk., Results: A total of 1,428 patients diagnosed with AIH from 1980 to 2020 from 22 eligible centres across Europe and Canada were included, with a median follow-up of 11.1 years (interquartile range 5.2-15.9). Two hundred and ninety-three (20.5%) patients had cirrhosis at diagnosis. During follow-up, 24 patients developed HCC (1.7%), an incidence rate of 1.44 cases/1,000 patient-years; the cumulative incidence of HCC increased over time (0.6% at 5 years, 0.9% at 10 years, 2.7% at 20 years, and 6.6% at 30 years of follow-up). Patients who developed cirrhosis during follow-up had a significantly higher incidence of HCC. The cumulative incidence of HCC was 2.6%, 4.6%, 5.6% and 6.6% at 5, 10, 15, and 20 years after the development of cirrhosis, respectively. Obesity (hazard ratio [HR] 2.94, p = 0.04), cirrhosis (HR 3.17, p = 0.01), and AIH/PSC variant syndrome (HR 5.18, p = 0.007) at baseline were independent risk factors for HCC development., Conclusions: HCC incidence in AIH is low even after cirrhosis development and is associated with risk factors including obesity, cirrhosis, and AIH/PSC variant syndrome., Impact and Implications: The risk of developing hepatocellular carcinoma (HCC) in individuals with autoimmune hepatitis (AIH) seems to be lower than for other aetiologies of chronic liver disease. Yet, solid data for this specific patient group remain elusive, given that most of the existing evidence comes from small, single-centre studies. In our study, we found that HCC incidence in patients with AIH is low even after the onset of cirrhosis. Additionally, factors such as advanced age, obesity, cirrhosis, alcohol consumption, and the presence of the AIH/PSC variant syndrome at the time of AIH diagnosis are linked to a higher risk of HCC. Based on these findings, there seems to be merit in adopting a specialized HCC monitoring programme for patients with AIH based on their individual risk factors., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: In patients with portal hypertension (PH), the differential diagnosis between porto-sinusoidal vascular disease (PSVD) and cirrhosis is challenging. This study aims to evaluate the diagnostic accuracy of the SSM/LSM index in the diagnosis of PSVD., Methods: Prospective study of patients with PH and PSVD or cirrhosis. Transient liver and spleen elastography were performed and the ratio between spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) was calculated. The relation of SSM/LSM with the diagnosis of PSVD was evaluated., Results: Forty-four patients with PSVD and 44 patients with cirrhosis were evaluated. Median age was 57.5 (IQR 49.0-64.5) years, 66.3% were males. In patients with PSVD, median SSM was 59.4 (33.5-77.7) kPa, median LSM was 6.2 (5.2-10.2) kPa and median SSM/LSM was 5.62 (3.15-9.68). In patients with cirrhosis, median SSM was 47.3 (24.3-60.3) kPa, median LSM was 27.8 (17.7-53.9) kPa and median SSM/LSM was 1.55 (1.06-3.24). The SSM/LSM AUROC was 0.940 (p<0.001). Using 2 as a cut-off, we obtained good sensitivity (86.5%), specificity (92.7%), and accuracy (89.7%) for the diagnosis of PSVD., Conclusion: The SSM/LSM index is useful in the differential diagnosis between liver cirrhosis and PSVD. Using the cut-off of 2 we achieved a good sensitivity and specificity for diagnosing PSVD., Competing Interests: Conflict of Interest None of the authors acted as Reviewer or Editor of this article. There are no conflicts of interest or financial ties to disclose. All authors disclosed no financial relationships relevant to this publication., (Copyright © 2022. Published by Elsevier Ltd.)

Backround: In acute severe autoimmune hepatitis (AS-AIH), the early identification of predictors of non-response to corticosteroids and the optimal timing for liver transplantation (LT) remains controversial., Aims: To determine early predictors of non-response to corticosteroids and to assess the usefulness of severity scores, namely the recently developed SURFASA., Methods: Retrospective multicentre cohort study including consecutive patients admitted for AS-AIH between 2016 and 2020. Definitions- response to corticosteroids: LT-free survival at 90 days (D90); SURFASA score: -6.8 + 1.92x(D0-INR)+1.94xINR[(D3-D0)/D0]+1.64xbilirubin[(D3-D0)/D0]., Results: We included 26 patients [median age 56 (45-69) years; 22 (84.6%) women]. All patients underwent corticosteroid therapy. Overall survival reached 73%. amongst the non-responders, 2 (7.8%) underwent LT and 5 (19.2%) died. The interval between admission and initiation of corticosteroids was not different between responders and non- responders [13 (7-23) vs. 8 (3-10), P:0.06], respectively. SURFASA and MELD-Na + (D3) scores showed an AUROC of 0.96 (0.87-1) and 0.92 (0.82-0.99), respectively, for prediction of non-response. SURFASA >-2.5 had a sensitivity of 85.7% and a specificity of 100% and MELD-Na + (D3) >26 had sensitivity of 85.7% and a specificity of 78% for the prediction of non-response., Conclusions: SURFASA and MELD-Na + at D3 scores are useful in early identification of non-responders to corticosteroids., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

This study aimed to morphologically and molecularly detect Hepatozoon procyonis in ring-tailed coatis' (Nasua nasua) blood and associated ticks from central-western Brazil, Campo Grande, Mato Grosso do Sul state and also evaluate the impact of the protozoa in blood parameters and coati´s health. Samplings were performed in a conservation area Parque Estadual do Prosa (PEP) and in a Brazilian Air Force Private Area namely Vila da Base Aérea (VBA), between March 2018 and April 2019. We collected 165 blood samples, 61 from recaptured coatis. Peripheral blood smears were stained with Romanovsky-type stain for H. procyonis parasitemia assessment. DNA extracted from blood samples and ticks (Amblyomma spp.) were submitted to a nested PCR (nPCR) assay based on the 18S rRNA gene for Hepatozoon spp. Out of 104 individuals sampled, 80 (77%) were positive for H. procyonis in at least one capture. Overall, 67/165 (40.6%) blood smears showed H. procyonis gametocytes (PEP: 41/63 - 65%; VBA: 26/102 - 25.5%). Parasitemia based on 500 assessed leucocytes ranged from 1 (0.2%) to 50 (10%) and 1 (0.2%) to 25 (5%), from animals sampled in PEP and VBA, respectively. Fluctuation on the parasitemia was observed during recaptures. nPCR results showed higher positivity when compared to blood smears, i.e. 112/165 (68%) positive blood samples [PEP: 41/63 (65%), VBA: 26/102 (25.5%)]. In total, 63/248 (25.4%) tick DNA samples were positive at nPCR for Hepatozoon sp., including 32/87 (37%) pools (1 to 10 larvae) of Amblyomma larvae, 21/105 (20%) pools (1 to 5 nymphs) of Amblyomma sculptum nymphs, 9/43 (21%) pools (1 to 5 nymphs) of Amblyomma dubitatumnymphs, and 1/12 (8%) A. sculptum adult female. The partial 18S rRNA sequence from one coati's blood sample and one representative of each positive tick species randomly selected from each area for sequencing (1,000 bp) showed 100% identity with sequences of H. procyonis from GenBank previously detected in coatis. Regarding H. procyonis infection, no statistical differences were obtained when comparing males vs. females (p-value 0.67), immature animals vs. adults (p-value 0.31), rainy vs. dry season (p-value 0.51) and sampling location (p-value 0.42). No noticeable alteration in blood parameters or heath status was observed in parasite animals. H. procyonis circulates in a high prevalence in coatis from central-western Brazil. Parasitemia fluctuates among different coatis' recaptures and apparently the infection has no influence in coatis' hematological and clinical parameters., (Copyright © 2022. Published by Elsevier GmbH.)

Background and Aims: Pancreatic ductal adenocarcinoma (PDAC) diagnosis can be difficult in a chronic pancreatitis (CP) background, especially in its mass forming presentation. We aimed to assess the accuracy of glypican-1-positive circulating exosomes (GPC1 + crExos) to distinguish PDAC from CP versus the state-of-the-art CA 19-9 biomarker., Methods: This was a unicentric prospective cohort. Endoscopic ultrasound with fine-needle aspiration or biopsy and blood tests (GPC1 + crExos and serum CA 19-9) were performed., Results: The cohort comprised 60 PDAC and 29 CP (7 of which mass forming - MF) patients. Median levels of GPC1 + crExos were significantly higher in PDAC (99.7%) versus CP (28.4%; p<0.0001) with an AUROC of 0.96 with 98.3% sensitivity and 86.2% specificity for a cut-off of 45.0% (p<0.0001); this outperforms CA 19-9 AUROC of 0.82 with 78.3% sensitivity and 65.5% specificity at a cut-off of 37 U/mL (p<0.0001). The superiority of% GPC1+crExos over CA 19-99 in differentiating PDAC from CP was observed in both early (stage I) and advanced tumors (stages II-IV)., Conclusion: Levels of GPC1 + crExos coupled to beads enable differential diagnosis between PDAC and CP including its mass-forming presentation., Competing Interests: Declaration of Competing Interest S. A. M. has ownership interests (patents). All other authors disclosed no potential conflicts of interest or financial relationships relevant to this publication., (Copyright © 2021. Published by Elsevier Ltd.)

Neratinib is an irreversible, pan-human epidermal growth factor inhibitor that has shown efficacy across human epidermal growth factor receptor 2 (HER2)-positive breast cancer settings. Neratinib is indicated for use as extended adjuvant therapy for HER2-positive early-stage breast cancer or, in combination with capecitabine, in the treatment of HER2-positive metastatic breast cancer. The primary tolerability concern with neratinib is diarrhea, and severe diarrhea early in treatment can lead to a substantial proportion of patients discontinuing neratinib, which may lead to reduced or nonexistent efficacy. In order to establish a set of treatment recommendations for use of neratinib, on May 12, 2020, an expert panel of oncologists and gastroenterologists met virtually to discuss the role of neratinib in the treatment of patients with HER2-positive breast cancer. The panel reviewed the current data on neratinib, including efficacy across settings and diarrhea management strategies. Based on these data and their clinical experience, the panelists developed a set of recommendations to guide selection of patients for neratinib, implement weekly dose escalation at initiation of therapy, and prophylactically manage diarrhea., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Application of animal manure to soils results in the introduction of manure-derived bacteria and their antimicrobial resistance genes (ARGs) into soils. ResCap is a novel targeted-metagenomic approach that allows the detection of minority components of the resistome gene pool without the cost-prohibitive coverage depths and can provide a valuable tool to study the spread of antimicrobial resistance (AMR) in the environment. We used high-throughput sequencing and qPCR for 16S rRNA gene fragments as well as ResCap to explore the dynamics of bacteria, and ARGs introduced to soils and adjacent water ditches, both at community and individual scale, over a period of three weeks. The soil bacteriome and resistome showed strong resilience to the input of manure, as manuring did not impact the overall structure of the bacteriome, and its effects on the resistome were transient. Initially, manure application resulted in a substantial increase of ARGs in soils and adjacent waters, while not affecting the overall bacterial community composition. Still, specific families increased after manure application, either through the input of manure (e.g., Dysgonomonadaceae) or through enrichment after manuring (e.g., Pseudomonadaceae). Depending on the type of ARG, manure application resulted mostly in an increase (e.g., aph(6)-Id), but occasionally also in a decrease (e.g., dfrB3) of the absolute abundance of ARG clusters (FPKM/kg or L). This study shows that the structures of the bacteriome and resistome are shaped by different factors, where the bacterial community composition could not explain the changes in ARG diversity or abundances. Also, it highlights the potential of applying targeted metagenomic techniques, such as ResCap, to study the fate of AMR in the environment., 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 © 2021. Published by Elsevier B.V.)

Manure application can spread antimicrobial resistance (AMR) from manure to soil and surface water. This study evaluated the role of the soil texture on the dynamics of antimicrobial resistance genes (ARGs) in soils and surrounding surface waters. Six dairy farms with distinct soil textures (clay, sand, and peat) were sampled at different time points after the application of manure, and three representative ARGs sul1, erm(B), and tet(W) were quantified with qPCR. Manuring initially increased levels of erm(B) by 1.5 ± 0.5 log copies/kg of soil and tet(W) by 0.8 ± 0.4 log copies/kg across soil textures, after which levels gradually declined. In surface waters from clay environments, regardless of the ARG, the gene levels initially increased by 2.6 ± 1.6 log copies/L, after which levels gradually declined. The gene decay in soils was strongly dependent on the type of ARG (erm(B) < tet(W) < sul1; half-lives of 7, 11, and 75 days, respectively), while in water, the decay was primarily dependent on the soil texture adjacent to the sampled surface water (clay < peat < sand; half-lives of 2, 6, and 10 days, respectively). Finally, recovery of ARG levels was predicted after 29-42 days. The results thus showed that there was not a complete restoration of ARGs in soils between rounds of manure application. In conclusion, this study demonstrates that rather than showing similar dynamics of decay, factors such as the type of ARG and soil texture drive the ARG persistence in the environment., 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 © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Complications of cirrhosis are one the major causes of hospital admission associated with high morbimortality rates and social and economic charges. The aims of this study were to evaluate hospital readmission and mortality rates and predictive factors for hospital readmission and mortality., Methods: Patients with decompensated cirrhosis admitted to our institution between 2008-2014 were retrospectively analyzed., Results: Included 427 admissions from 177 patients with cirrhosis with mean age of 59.0 ± 12.3 years. The major cause was alcoholic-related liver disease and the median duration of admission was 9.0 days (IQR 6.0-14.0). During the follow-up period,there were 250 readmissions from 95 patients, with a median of 58 (IQR27-134) days for readmission, representing 58.5% of the total number of admissions.The 180-day mortality rate was 35.0%. In the multivariate analysis, ascites, smoking and MELD Na were associated with 180-day mortality. Creatinine, albumin, esophageal variceal bleeding, previous variceal banding, lactulose, rifaximin and proton pump inhibitors use were independently associated with need of readmission. Based on regression analysis, two models were calculated to predict 180-day mortality (AUROC 0.74 (0.682-0.794)) and need for readmission(AUROC 0.821 (0.781-0.861)), p < 0.001., Conclusion: The readmission rate and mortality of cirrhotic patients are still very high and it is a priority to determine preventable risk factors to improve patient outcome. Two models were created to predict 180-day mortality(AUROC 0.74) and need for readmission(AUROC 0.821), that could guide the management of the patients at the time of admission., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Compare efficacy, safety and long-term outcomes of bridge-to-surgery and emergency surgery in acute malignant colorectal obstruction., Methods: Retrospective study of 94 consecutive patients with left-sided acute malignant colorectal obstruction treated with curative intent between 2010-2017., Results: 48 patients underwent stent placement and 46 underwent emergency surgery. Technical and clinical success were 100% and 87%. Laparoscopy and one-staged operation were more frequent in bridge-to-surgery (44% vs 2%, p < 0.001; 73% vs 30%, p < 0.001). Fewer permanent stomas were created in bridge-to-surgery (15% vs 35%, p = 0.013). Overall morbidity was 36%. Immediate and post-procedure stent related-complications occurred in 6% and 13%; surgery-related complications occurred in 28% (bridge-to-surgery: 15% vs emergency surgery: 41%, p = 0.004). No differences were found regarding tumor recurrence, recurrence-free survival and overall survival. R1 resection (HR 47.2, 95% CI:4.1-543.7), number of lymph nodes harvested (HR 0.9 95% CI:0.8-0.99) and adjuvant therapy (HR 0.1 95% CI:0.01-0.9) predicted recurrence-free survival; pTMN stage IV (HR 7.3, 95% CI:1.1-47.6), number of lymph nodes harvested (HR 0.90, 95% CI:0.8-0.97), adjuvant therapy (HR 0.1, 95% CI:0.02-0.4) and surgery-related complications (HR 5.3, 95% CI:1.02-27.3) influenced overall survival., Conclusion: Stent placement has a high success, similarly to emergency surgery, being associated with higher primary anastomosis and lower stoma rates. Tumor recurrence rate, recurrence-free survival and overall survival were comparable between groups; surgery-related complications influenced overall survival., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The main objective of this study was to evaluate the effect of intramuscular (I.M.) administration of different doses of kisspeptin (Kp) on the pattern of luteinizing hormone (LH) release in Bos taurus and Bos indicus prepubertal heifers. Holstein heifers weighing 215.1 ± 38.6 kg (n = 24; aged 5-8 mo) and Gyr heifers weighing 215.4 ± 31.4 kg (n = 24; aged 6-10 mo) were enrolled in this study. The animals were confirmed as non-cyclical by absence of a corpus luteum (CL) as determined by ultrasound scanning of the ovaries and low circulating P4 concentrations (<1.0 ng/mL) evaluated at a 10-day interval (on day -10 and day 0). For each genetic group, heifers were randomly assigned to one of four treatments: Kp at 2.5 μg/kg body weight (Kp2.5), Kp at 5.0 μg/kg (Kp5), Kp at 10 μg/kg (Kp10), or gonadotropin-releasing hormone (GnRH) agonist (0.01 mg of buserelin acetate per heifer), all administered by I.M. injection. All animals responded to the treatments with an LH surge (P < 0.01). There was an effect of breed (P < 0.01) on induced LH release, with Holstein heifers having a greater area under the curve for LH (AUC; P < 0.01) and greater LH peak amplitude (P < 0.01) than Gyr heifers. Nevertheless, greater AUC for LH occurred in Kp10 heifers for both breeds. There was no effect of breed on LH AUC or LH peak amplitude after GnRH agonist treatment. For both breeds, heifers treated with Kp displayed an earlier (P < 0.01) LH peak with a reduced amplitude of the LH peak (P < 0.01) and reduced LH AUC (P < 0.01) compared to heifers treated with GnRH agonist. Thus, both zebu and taurus immature heifers treated with I.M. Kp injection responded with a rapid and dose-dependent LH surge, although even large doses of the native Kp-10 did not mimic the magnitude or duration of the LH surge produced by the GnRH agonist. The early onset of the LH surge after Kp treatment and the short duration suggest that the effects of Kp were likely due to pituitary rather than hypothalamic action. Finally, there seems to be a greater responsiveness to Kp in Bos taurus than in Bos indicus prepubertal heifers, although LH release after GnRH agonist treatment was similar for the two breeds., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pancreatic cancer (PC) is one of the deadliest cancers with a 5-year overall survival of less than 6%. Due to its insidious clinical course and unspecific symptoms, the diagnosis is usually late, with only 15-20% patients presenting with potentially curable disease. It is, therefore, extremely important to identify patients with PC at early stages of the disease when tumors may be amenable to surgical resection. For unresectable and borderline resectable PC it is consensual to perform a biopsy to have a cyto/histological confirmation of malignancy before treatment. However, for patients presenting with promptly resectable disease, the role of biopsy is more debatable. There are, in the literature, arguments both for and against the usefulness of a preoperative biopsy. Endoscopic ultrasound (EUS) is an important technique assisting in the diagnosis and staging of PC. EUS-guided tissue acquisition is a well-established tool to demonstrate the malignant nature of a pancreatic lesion. This review focuses on the role of EUS in the diagnosis and staging of PC, and highlights the controversy related to the role of EUS-guided tissue acquisition in the preoperative assessment of patients presenting with promptly resectable tumors (early PC)., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Training in endoscopic retrograde cholangiopancreatography (ERCP) requires the development of technical, cognitive, and integrative skills well beyond those needed for standard endoscopic procedures. So far, there are limited data regarding what constitutes competency in ERCP, including achievement and maintenance. Recent studies have highlighted overall procedural numbers are not enough to warrant competency, although more is better. We performed a comprehensive literature search until June 2017 using predetermined search terms to identify relevant articles and summarized their results as a narrative review. Selective native papilla deep cannulation should be used as a benchmark for assessing successful cannulation. Accurate and validated ERCP performance measures are needed to develop a curriculum that allows transition from numbers-based competency. However, available guidelines fail to state what degree of hands-on involvement is required by the trainee for the case to be counted in their overall procedural numbers. Qualitative assessment of competency should be done by trained raters using specially designed assessment tools. Competence continues to increase with practice following formal training in a fairly steady manner. The learning curve for overall common bile duct cannulation success may be a readily available surrogate for individual trainee progression and may correspond to learning curves for therapeutic interventions., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Conventional wastewater treatment has a limited capacity to reduce antibiotic resistant bacteria and genes (ARB&ARG). Tertiary treatment processes are promising solutions, although the transitory inactivation of bacteria may select ARB&ARG. This study aimed at assessing the potential of ozonation and UV 254nm radiation to inactivate cultivable fungal and bacterial populations, and the selected genes 16S rRNA (common to all bacteria), intI1 (common in Gram-negative bacteria) and the ARG vanA, bla TEM , sul1 and qnrS. The abundance of the different microbiological parameters per volume of wastewater was reduced by ∼2 log units for cultivable fungi and 16S rRNA and intI1 genes, by∼3-4 log units, for total heterotrophs, enterobacteria and enterococci, and to values close or below the limits of quantification for ARG, for both processes, after a contact time of 30min. Yet, most of the cultivable populations, the 16S rRNA and intI1 genes as well as the ARG, except qnrS after ozonation, reached pre-treatment levels after 3days storage, suggesting a transitory rather than permanent microbial inactivation. Noticeably, normalization per 16S rRNA gene evidenced an increase of the ARG and intI1 prevalence, mainly after UV 254 nm treatment. The results suggest that these tertiary treatments may be selecting for ARB&ARG populations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Disinfection processes aim at reducing the number of viable cells through the generation of damages in different cellular structures and molecules. Since disinfection involves unspecific mechanisms, some microbial populations may be selected due to resilience to treatment and/or to high post-treatment fitness. In this study, the bacterial community composition of secondarily treated urban wastewater and of surface water collected in the intake area of a drinking water treatment plant was compared before and 3-days after disinfection with ultraviolet radiation, ozonation or photocatalytic ozonation. The aim was to assess the dynamics of the bacterial communities during regrowth after disinfection. In all the freshly collected samples, Proteobacteria and Bacteroidetes were the predominant phyla (40-50% and 20-30% of the reads, respectively). Surface water differed from wastewater mainly in the relative abundance of Actinobacteria (17% and <5% of the reads, respectively). After 3-days storage at light and room temperature, disinfected samples presented a shift of Gammaproteobacteria (from 8 to 10% to 33-65% of the reads) and Betaproteobacteria (from 14 to 20% to 31-37% of the reads), irrespective of the type of water and disinfection process used. Genera such as Pseudomonas, Acinetobacter or Rheinheimera presented a selective advantage after water disinfection. These variations were not observed in the non-disinfected controls. Given the ubiquity and genome plasticity of these bacteria, the results obtained suggest that disinfection processes may have implications on the microbiological quality of the disinfected water., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Neurosurgery simulation has gained attention recently due to changes in the medical system. First-year neurosurgical residents in low-income countries usually perform their first craniotomy on a real subject. Development of high-fidelity, cheap, and largely available simulators is a challenge in residency training. An original model for the first steps of craniotomy with cerebrospinal fluid leak avoidance practice using a coconut is described., Material and Methods: The coconut is a drupe from Cocos nucifera L. (coconut tree). The green coconut has 4 layers, and some similarity can be seen between these layers and the human skull. The materials used in the simulation are the same as those used in the operating room., Procedure: The coconut is placed on the head holder support with the face up. The burr holes are made until endocarp is reached. The mesocarp is dissected, and the conductor is passed from one hole to the other with the Gigli saw. The hook handle for the wire saw is positioned, and the mesocarp and endocarp are cut. After sawing the 4 margins, mesocarp is detached from endocarp. Four burr holes are made from endocarp to endosperm. Careful dissection of the endosperm is done, avoiding liquid albumen leak. The Gigli saw is passed through the trephine holes. Hooks are placed, and the endocarp is cut. After cutting the 4 margins, it is dissected from the endosperm and removed. The main goal of the procedure is to remove the endocarp without fluid leakage., Discussion: The coconut model for learning the first steps of craniotomy and cerebrospinal fluid leak avoidance has some limitations. It is more realistic while trying to remove the endocarp without damage to the endosperm. It is also cheap and can be widely used in low-income countries. However, the coconut does not have anatomic landmarks. The mesocarp makes the model less realistic because it has fibers that make the procedure more difficult and different from a real craniotomy., Conclusion: The model has a potential pedagogic neurosurgical application for freshman residents before they perform a real craniotomy for the first time. Further validity is necessary to confirm this hypothesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction/objectives: A histological classification system (AHHS) has been recently proposed to predict 90-day mortality in patients with alcoholic hepatitis (AH). We analyzed the spectrum of histological features in patients with AH and assessed the ability of AHHS for predicting both response to steroids and 90-day mortality., Methods: Retrospective study of patients admitted to our tertiary centre between 2010 and 2014 with biopsy-proven AH. Histological features were analyzed and AHHS value was calculated. Kaplan-Meyer curves were calculated to assess the ability of AHHS to predict response to steroids and 90-day mortality., Results: We included 34 patients (70.6% men, mean age 48.5±8.9 years). Transjugular liver biopsy was performed 3.5±2.9 days after admission. Presence of bilirubinostasis (p=0.049), degree of bilirubinostasis (p<0.001), absence of megamitochondria (p<0.001) and degree of polymorphonuclear infiltration (p=0.018) were significantly associated with higher mortality at 90 days. Patients who responded to steroids had a significantly lower AHHS value than non-responders (5.4±0.9 vs 8.1±1.1, p=0.003). AAHS value was significantly higher in patients who died compared to patients who survived at 90 days (9.0±0.7 vs 5.0±0.9, p<0.001). AHHS predicted response to steroids [AUROC 0.90 (CI95% 0.742-1.000), p=0.004] and 90-day mortality [AUROC 1.0 (CI95% 1.0-1.0), p<0.001] with high accuracy., Conclusions: In this cohort of patients, presence and degree of bilirubinostasis, absence of megamitochondria and degree of PMN infiltration were significantly associated with 90-day mortality. AHHS had a high accuracy for predicting response to steroids and 90-day mortality in this cohort of patients., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The present study evaluated the effect of the type of norgestomet ear implant (new vs. used) on the ovarian follicular response (experiment 1) and pregnancy per artificial insemination (AI) (P/AI; experiment 2) of beef heifers subjected to an estradiol plus progestin timed artificial insemination (TAI) program. In experiment 1, 57 cyclic beef heifers were randomly assigned to one of two groups according to the type (new or previously used for 9 days) of norgestomet ear (NORG) implant. At the time of NORG implant insertion, the heifers were treated with 2 mg of intramuscular estradiol benzoate. Eight days later, the NORG implants were removed, and the heifers received an intramuscular administration of 150 μg of d-cloprostenol, 300 IU of equine chorionic gonadotropin, and 0.5 mg of estradiol cypionate. The heifers had their ovaries scanned every 12 hours from the time of NORG implant removal to 96 hours after verifying the occurrence and timing of ovulation. No difference (P = 0.89) was observed in the ovulation rates between the two treatments (new = 80.0%; 24/30 vs. used = 81.5%; 22/27). However, the heifers treated with a used NORG implant had (P = 0.04) higher proportion (36.4%; 8/22) of early ovulation (between 36 and 48 hours after NORG implant removal) compared with the heifers treated with a new NORG implant (8.3%; 2/24). In experiment 2, at the beginning of the synchronization protocol, 416 beef heifers were randomly assigned into two groups, as described in the experiment 1. Two days after the NORG implant removal, the heifers were reassigned to be inseminated at 48 or 54 hours after NORG implant removal. There was an interaction (P = 0.03) between the type of NORG implant and the timing of TAI on P/AI. The timing of insemination only had an effect (P = 0.02) on the P/AI when the heifers were treated with a used NORG implant [(TAI 54 hours = 41.9% (44/105) vs. TAI 48 hours = 58.6% (58/99)]. In conclusion, beef heifers synchronized with a used NORG implant plus estradiol exhibited a higher proportion of earlier ovulations, and TAI in these heifers should be performed 48 hours after removal of used NORG implants., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Defects in macrophage function have been implicated in the establishment of Crohn's disease (CD). However, the response of macrophages from CD patients to live bacteria, particularly Mycobacterium avium subsp. paratuberculosis (MAP), has not been addressed. Considering MAP has long been associated to CD, our objective was to assess whether macrophages from CD patients showed impaired inflammatory response to infection by MAP comparing to M. avium subsp. avium (MA) and other live intestinal commensal bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, ulcerative colitis (UC) patients and controls. Following in vitro infection with MAP, MA, Escherichia coli or Enterococcus faecalis, cytokine levels and cell surface receptor expression were evaluated at different time points. Macrophages from CD patients showed impaired TNF-α secretion in response to bacterial challenge, but augmented IL-23 secretion and preserved IL-12 secretion and CD-40 expression. In addition, CD macrophages showed low IL-10 secretion. Macrophages from IBD patients showed increased expression of TLR-2 and -4, unaffected by infection. Differences in cytokine secretion observed after bacterial challenge were not MAP-specific, as other bacteria (E. coli and MA) showed similar effects. Macrophages from UC patients showed a less compromised TNF-α synthesis in response to mycobacterial infection than CD macrophages, with increased constitutive IL-12 secretion, and preserved IL-10 secretion. The increased IL-23 levels in response to infection and decreased IL-10 production observed in macrophages from CD patients may contribute to the inflammatory exacerbation observed in those patients., (Copyright © 2011 Elsevier GmbH. All rights reserved.)