To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD).
Caecal biopsies were ...collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grade inflammation was evaluated by counting cells, including intraepithelial lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and protein expression of tumour necrosis factor (TNF)-α in biopsies and culture supernatants.
IBS-like symptoms were present in 35.4 and 38% of CD and UC patients, respectively. Paracellular permeability was significantly increased in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01, respectively). Significantly lower expression of ZO-1 and α-catenin was detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-α were significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS.
In quiescent IBD, IBS-like symptoms related to persistent subclinical inflammation associated with increased colonic paracellular permeability. A persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects associated with abdominal pain in quiescent IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered in quiescent IBD with IBS-like symptoms.
The energetic convenience of electrolytic water splitting is limited by thermodynamics. Consequently, significant levels of hydrogen production can only be obtained with an electrical energy ...consumption exceeding 45 kWh kg(-1)H2. Electrochemical reforming allows the overcoming of such thermodynamic limitations by replacing oxygen evolution with the oxidation of biomass-derived alcohols. Here we show that the use of an original anode material consisting of palladium nanoparticles deposited on to a three-dimensional architecture of titania nanotubes allows electrical energy savings up to 26.5 kWh kg(-1)H2 as compared with proton electrolyte membrane water electrolysis. A net energy analysis shows that for bio-ethanol with energy return of the invested energy larger than 5.1 (for example, cellulose), the electrochemical reforming energy balance is advantageous over proton electrolyte membrane water electrolysis.
In the north‐western Mediterranean area, the first Iron Age is characterized by intense contacts and cultural interactions between populations. Archaeological remains such as ceramic vessels or metal ...and glass objects are usually good indicators of the nature and the intensity of these exchanges, but can also be used to determine the way in which these populations were living at their time. In contrast, organic substances, despite their importance in a wide variety of activities, are rarely investigated due to their low degree of preservation. The recent discovery of a series of amorphous organic residues with adhesive properties at the site of Cuciurpula provided a unique opportunity to address questions related to the types of natural substances exploited, their provenance, their uses and their informational input to intercultural relationships. Our results, based on GC and GC–MS analysis of organic residues preserved at the site of Cuciurpula, provide strong evidence for the most southern use of birch bark tar in Western Europe, and also for the simultaneous use of this substance with pine resin. Beeswax was also identified in some samples. The combined study of residue composition, aspect and location on ceramic sherds reveals a variety of uses, highlighting a complex technical system.
Summary
Background
Long‐term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated.
Aim
To evaluate the long‐term efficacy and safety of ustekinumab and identify the predictive ...factors of ustekinumab failure‐free persistence in a cohort of anti‐TNF refractory CD patients.
Methods
We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD‐related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery.
Results
Eighty‐eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4‐34.4) months. Forty‐seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure‐free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure‐free persistence was identified. One severe adverse event was observed (anal adenocarcinoma).
Conclusion
In this cohort of refractory CD patients receiving long‐term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.
Summary
Background
We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti‐TNF failure in a multicentre compassionate ...early‐access programme before marketing authorisation was granted to vedolizumab.
Aims
To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD.
Methods
Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey‐Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid‐free clinical remission at week 54.
Results
At week 54, steroid‐free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid‐free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation.
Conclusion
Vedolizumab is able to maintain steroid‐free clinical remission in up to one‐third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.
Linked ContentThis article is linked to Speight and Mansfield papers. To view this article visit https://doi.org/10.1111/apt.14215.
Purpose To determine the respective functions of the anterior cruciate ligament (ACL) and the anterolateral structures (ALSs) in controlling the tibia's passive internal rotation (IR) with respect to ...the femur, under uniaxial rotation. Methods To test the function of the ACL and the anterolateral ligament (ALL) in IR, we designed a sequential transection study of the ACL and the anterolateral structures (including the ALL) in 24 cadaveric knees divided in 2 groups. Two sequences were conducted successively: group 1 (12 knees) in which the ACL was sectioned first followed by the ALS, and group 2 (12 knees) with reversed transections. Each knee, in neutral rotation position and at flexion angle of 30°, was subjected to a 5 Nm torsion torque of IR. IR was measured using a rotatory laximeter, the Rotam with a gyroscope's measurement accuracy of 0.1°. Laxities were compared using paired t test within each group and using t test between groups. Fisher exact test was used to compare proportions. Results In group 1, IR increased from 22.1° ± 10.6° to 25.7° ± 10.9° after ACL transection then to 28.1° ± 10.5° after we sectioned the ALS. In group 2, IR increased from 22.5° ± 8.9° to 25.2° ± 8.4° after sectioning the ALS, then to 29.1° ± 8.8° after we sectioned the ACL. Total postsectioning increase in IR was 6.4° ± 2° in group 1, and 6.55° ± 0.9° in group 2. The IR increase after each stage of transection and final IR were statistically significant ( P < .001). Conclusions In a pure rotational cadaveric test model, the ACL and the ALS contribute to resistance to passive IR of the knee. Clinical Relevance In some specific clinical cases, peripheral lesions may be considered, and injuries to these structures may need to be addressed to improve results controlling postoperative IR.
High-throughput phenotyping is becoming increasingly available thanks to analytical and bioinformatics approaches that enable the use of very high-dimensional data and to the availability of dynamic ...models that link phenomena across levels: from genes to cells, from cells to organs, and through the whole organism. The combination of phenomics, deep learning, and machine learning represents a strong potential for the phenotypical investigation, leading the way to a more embracing approach, called machine learning phenomics (MLP). In particular, in this work we present a novel MLP platform for phenomics investigation of cancer-cells response to therapy, exploiting and combining the potential of time-lapse microscopy for cell behavior data acquisition and robust deep learning software architectures for the latent phenotypes extraction. A two-step proof of concepts is designed. First, we demonstrate a strict correlation among gene expression and cell phenotype with the aim to identify new biomarkers and targets for tailored therapy in human colorectal cancer onset and progression. Experiments were conducted on human colorectal adenocarcinoma cells (DLD-1) and their profile was compared with an isogenic line in which the expression of LOX-1 transcript was knocked down. In addition, we also evaluate the phenotypic impact of the administration of different doses of an antineoplastic drug over DLD-1 cells. Under the omics paradigm, proteomics results are used to confirm the findings of the experiments.
•Alkaline Platinum-free formate fuel cells top 42% efficiency @ 60°C.•Palladium efficiently oxidizes formate.•Power density exceeding 250mWcm−2 @ 60°C has been achieved.•Performance exceeds that of ...Alkaline Direct Alcohol Fuel Cell.
We report the energy performance of a new platinum-free alkaline direct formate fuel cell, equipped with a commercial anion exchange membrane, a nanostructured Pd/C anode and a Fe–Co/C cathode. The cell was investigated both at room temperature and at 60°C for the determination of the following parameters: (i) maximum power density, (ii) delivered energy, (iii) faradic (fuel conversion) and energy efficiency. These parameters show a dramatic dependence on fuel composition. The highest energy efficiency is obtained using high energy density fuel (4M KCOOH and 4M KOH) and with a maximum operating temperature of 60°C. This represents a key step in the progress of alkaline platinum-free DFFC technology, demonstrating their potential as power sources for portable electronic devices and remote power generation systems. For example, a fuel load of 750ml in a DFFC device operating at 60°C would be able to produce 90Wh of energy, that required to fully charge the battery of a laptop computer.
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