Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study

In this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living-related donor (LRD) or living-unrelated donor (LUD). Adult patients in the ERA-EDTA Registry who received their first kidney transplant in 1998-2017 were included. Ten-year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five-year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7-4.6) and 10.8% (95% CI: 10.1-11.5) versus 6.5% (95% CI: 5.7-7.4) and 12.2% (95% CI: 11.2-13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87-1.13) for patient survival and 1.03 (95% CI: 0.94-1.14) for graft survival. Unadjusted risk of death-censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04-1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death-censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.Peer reviewe

Expulsion of runaway electrons using ECRH in the TCV tokamak

Runaway electrons (REs) are a concern for tokamak fusion reactors from discharge startup to termination. A sudden localized loss of a multi-megaampere RE beam can inflict severe damage to the first wall. Should a disruption occur, the existence of a RE seed may play a significant role in the formation of a RE beam and the magnitude of its current. The application of central electron cyclotron resonance heating (ECRH) in the Tokamak \`a Configuration Variable (TCV) reduces an existing RE seed population by up to three orders of magnitude within only a few hundred milliseconds. Applying ECRH before a disruption can also prevent the formation of a post-disruption RE beam in TCV where it would otherwise be expected. The RE expulsion rate and consequent RE current reduction are found to increase with applied ECRH power. Whereas central ECRH is effective in expelling REs, off-axis ECRH has a comparatively limited effect. A simple 0-D model for the evolution of the RE population is presented that explains the effective ECRH-induced RE expulsion results from the combined effects of increased electron temperature and enhanced RE transport

An assessment of particulate organic carbon to thorium-234 ratios in the ocean and their impact on the application of 234Th as a POC flux proxy

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Chemistry 100 (2006): 213-233, doi:10.1016/j.marchem.2005.10.013.Thorium-234 is increasingly used as a tracer of ocean particle flux, primarily as a means to estimate particulate organic carbon export from the surface ocean. This requires determination of both the 234Th activity distribution (in order to calculate 234Th fluxes) and an estimate of the C/234Th ratio on sinking particles, to empirically derive C fluxes. In reviewing C/234Th variability, results obtained using a single sampling method show the most predictable behavior. For example, in most studies that employ in situ pumps to collect size fractionated particles, C/234Th either increases or is relatively invariant with increasing particle size (size classes >1 to 100’s μm). Observations also suggest that C/234Th decreases with depth and can vary significantly between regions (highest in blooms of large diatoms and highly productive coastal settings). Comparisons of C fluxes derived from 234Th show good agreement with independent estimates of C flux, including mass balances of C and nutrients over appropriate space and time scales (within factors of 2-3). We recommend sampling for C/234Th from a standard depth of 100 m, or at least one depth below the mixed layer using either large volume size fractionated filtration to capture the rarer large particles, or a sediment trap or other device to collect sinking particles. We also recommend collection of multiple 234Th profiles and C/234Th samples during the course of longer observation periods to better sample temporal variations in both 234Th flux and the characteristic of sinking particles. We are encouraged by new technologies which are optimized to more reliably sample truly settling particles, and expect the utility of this tracer to increase, not just for upper ocean C fluxes but for other elements and processes deeper in the water column.Individuals and science efforts discussed herein were supported by many national science programs, including the U.S. National Science Foundation and U.S. Department of Energy. S.F. and J.C.M. acknowledge the support provided to the International Atomic Energy Agency (IAEA) Marine Environment Laboratory by the Government of the Principality of Monaco. T.T. acknowledges support from the Australian Antarctic Science Program. K.B. was supported in part by a WHOI Ocean Life Institute Fellowship

Effects of pectin liquid on gastroesophageal reflux disease in children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>The use of thickeners is a standard therapy for decreasing episodes of regurgitation or vomiting in infants. However, it remains to be investigated whether thickener is effective for vomiting and/or chronic respiratory symptoms in children with cerebral palsy.</p> <p>Methods</p> <p>We enrolled 18 neurologically impaired children caused by cerebral palsy, with gastroesophageal reflux disease. In the first part of this study (pH monitoring), subjects were randomly allocated to two groups: fed with a high-pectin diet [enteral formula: pectin liquid = 2:1 (v/v)], or a low-pectin diet [enteral formula: pectin liquid = 3:1 (v/v)]. Two-channel esophageal pH monitoring was performed over 48 h. In the second part (clinical trial), subjects were fed a high- or low-pectin diet and non-pectin diet for 4 weeks in a crossover manner. Nurses recorded the feeding volume, number of episodes of vomiting, volume of gastric residue, episodes of cough and wheeze, frequency of using oxygen for dyspnea, and the day when the child could return to school. Cough and wheeze were recorded as a cough-score.</p> <p>Results</p> <p>The median value for the % time pH < 4 at the lower and upper esophagus was significantly decreased with a high-pectin diet [9.2% (6.2–22.6) vs. 5.0% (3.1–13.1); P < 0.01, 3.8% (2.9–11.2) vs. 1.6% (0.9–8.9); P < 0.01 (interquartile range), non-pectin and high-pectin, respectively]. The number of reflux episodes per day and duration of longest reflux were decreased significantly with a high-pectin, but not with a low-pectin diet. The median number of episodes of vomiting decreased significantly with a high-pectin diet [2.5/week (1.0–5.0) vs. 1.0 (1.0–1.5), P < 0.05]. The median cough-score was significantly decreased by both concentrations of pectin [8.5/week (1.0–11.5) vs. 2.0/week (0.0–3.0), fed with a high-pectin diet; 7.0/week (1.0–14.5) vs. 1.0/w (0.0–5.0), fed with a low-pectin diet, P < 0.05].</p> <p>Conclusion</p> <p>Pectin liquid partially decreased gastroesophageal reflux as measured by eshophageal pH monitoring, and might improve vomiting and respiratory symptoms in children with cerebral palsy.</p> <p>Trial registration</p> <p>ISRCTN19787793</p

Metastases from renal cell carcinoma presenting as gastrointestinal bleeding: two case reports and a review of the literature

BACKGROUND: Bleeding from small bowel neoplasms account for 1–4% of cases of upper gastrointestinal haemorrhage. Renal cell carcinoma constitutes 3% of all adult malignancies and often presents insidiously. Consequently 25–30% of patients have metastases at the time of diagnosis. Gastrointestinal bleeding from renal cell carcinoma metastases is an uncommon and under-recognised manifestation of this disease. CASE REPORT: In this report we describe two cases of gastrointestinal bleeding from renal cell carcinoma metastases – in one patient bleeding heralded the primary manifestation of disease and in the other signified recurrence of disease following nephrectomy. CONCLUSION: These cases highlight the importance endoscopic vigilance in cases of undiagnosed upper gastrointestinal haemorrhage, especially in patients with a past history of renal cell carcinoma