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Background/Objectives: There is a lack of certainty in dietary prescription for individuals with inflammatory bowel disease (IBD) due to heterogeneity in studies to date. The aim of this study was to investigate the efficacy on disease activity of a modified anti-inflammatory dietary pattern purposely designed to reduce intake of food additives (IBD-MAID), compared to standard care, in adults with IBD. Subject/Methods: Adults with IBD were randomised to IBD-MAID (meals provided) [n= 29] or general healthy eating (GHE) [n= 29] for 8 weeks. Disease activity, faecal calprotectin (FC), C-reactive protein (CRP), symptoms, and quality of life (S&QOL) were assessed using validated tools. Results: The IBD-MAID was well tolerated and adhered to (92% adherence). At week 8, there was no statistically significant difference in change from baseline in outcome measures between groups. However, baseline to week 8 analysis indicated: (1) statistically significant improvements in S (p= 0.001) & QOL (p= 0.004), FC (p= 0.007), and Crohn’s disease activity (p= 0.03) but not ulcerative colitis, in individuals following the IBD-MAID and (2) statistically significant improvement in QOL in individuals receiving GHE (p= 0.015). Correlation analysis on change from baseline to week 8 revealed a greater decrease in food additives intake was associated with statistically significant improvements in FC, S & QOL and alignment of anti-inflammatory dietary principles with improvements in QOL. Conclusion: The IBD-MAID was well tolerated. The most novel finding pertains to the correlation between reduced food additives intake and improvements in inflammatory markers, S&QOL. Further research is needed to explore the effects of food additives exposure on IBD course. Trial registration: 12619001500145

Branchpoint elements are required for intron removal, and variants at these elements can result in aberrant splicing. We aimed to assess the value of branchpoint annotations generated from recent large-scale studies to select branchpoint-abrogating variants, using hereditary cancer genes as model.

ABSTRACTCAV1 (caveolin 1) expression and secretion is associated with prostate cancer (PCa) disease progression, but the mechanisms underpinning CAV1 release remain poorly understood. Numerous studies have shown CAV1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) CAV1 topology. Here we show that CAV1 can be secreted from specific PCa types in an inverted vesicle-associated form consistent with the features of bioactive CAV1 secretion. Characterization of the isolated vesicles by electron microscopy, single-molecule fluorescence microscopy and proteomics reveals they represent a novel class of exosomes ~40 nm in diameter containing ~50-60 copies of CAV1 and, strikingly, are released via a non-canonical secretory macroautophagy/autophagy pathway. This study provides novel insights into a mechanism whereby CAV1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression.Abbreviations:3-MA: 3-methyladenine; APEX: a modified soybean ascorbate peroxidase; ATG5: autophagy related 5; ATG9A: autophagy related 9A; ATG12: autophagy related 12; BHK: baby hamster kidney; C-exosomes: caveolin-exosomes; CAMKK2/CAMKKβ: calckum/calmodulin dependent protein kinase kinase 2; CAV1: caveolin 1; DAB: 3,3′-diaminobenzidine; DAPK: death associated protein kinase; EEA1: early endosome antigen 1; EM: electron microscopy; FCS: fluorescence correlation spectroscopy; GBP: GFP/YFP-binding peptide; GFP: green fluorescent protein; GOLGA2: golgin A2; ILVs: intralumenal vesicles; LC3: microtubule-associated protein 1 light chain 3; MBP: maltose binding protein; MTORC1: mechanistic target of rapamycin kinase complex 1; MVBs: multivesicular bodies; PBS: phosphate-buffered saline; PCa: prostate cancer; PI3K: phosphoinositide 3-kinase; PM: plasma membrane; SFM: serum-free medium; TSG101: tumor susceptibility 101; WCL: whole cell lysates; WT: wild type; YFP: yellow fluorescent protein; βoG: β-octylglucoside

Peripheral nerve blocks can provide surgical anaesthesia as well as excellent postoperative analgesia. When questioned postoperatively, however, some patients report low levels of satisfaction with their nerve block experience. At our hospital, patients undergoing regional anaesthesia have their patient characteristics, block characteristics and postoperative feedback routinely recorded in a block registry. We analysed data from 979 consecutive patients undergoing peripheral nerve block for orthopaedic surgery to identify factors associated with low levels of patient satisfaction. The primary outcome was patient satisfaction with their peripheral nerve block (scale 1–5: 4–5 is ‘satisfied’, 1–3 is ‘not satisfied’). Eighty-nine percent (871/979) of patients reported being ‘satisfied’ with their block. Factors negatively associated with patient satisfaction were rebound pain (adjusted odds ratio (aOR) 0.19, 95% confidence interval (CI) 0.04 to 0.85 for moderate rebound pain; aOR 0.11, 95% CI 0.03 to 0.48 for severe rebound pain), discomfort during the block (aOR 0.37, 95% CI 0.16 to 0.82 for moderate discomfort; aOR 0.19, 95% CI 0.05 to 0.76 for severe discomfort) and pain in the post-anaesthesia care unit (aOR 0.30, 95% CI 0.17 to 0.55 for pain ≥8/10). Only 24% (26/108) of patients who reported being ‘not satisfied’ stated that they would be unwilling to undergo a hypothetical future nerve block. Rebound pain of at least moderate intensity, procedural discomfort of at least moderate intensity and severe pain in the post-anaesthesia care unit are all negatively associated with patient satisfaction. Of these factors, rebound pain occurs most frequently, being present in 52% (403/777) of our respondents.

Catheter-related thrombosis (CRT) is a complication of central venous access devices (CVADs). Evidence is variable regarding the significance of the side of catheter insertion. The role of the patient’s hand dominance in predisposition to CRT remains uncertain.

Therapeutic hypothermia (TH) after neonatal encephalopathy, commonly provided by 72 hours of whole-body cooling using a wrap, limits parents' physical contact with their infants affecting bonding and may not be suitable for encephalopathic preterm infants with fragile skin. Alternative cooling methods are unavailable for this population. We investigated in a neonatal pig model the feasibility of achieving a 3.5°C reduction in rectal temperature (Trectal) similar to clinical TH protocols from 38.5°C (normothermia for pigs) to a target of 35°C ± 0.2°C, using a novel neonatal esophageal heat exchanger (NEHE), compared its efficacy to passive cooling, and investigated its ability to maintain target Trectal. Ventilated and anesthetized Landrace/Large whitenewborn pigs had the NEHE inserted. Water at adjustable temperatures and rates flowed down a central tube, returning up a surrounding distensible blind ending latex tube in a continuous loop. An initial experiment guided four subsequent cycles of passive cooling (30 minutes), rewarming to 38.5°C, active esophageal cooling to 35°C ± 0.2°C, active maintenance of target Trectal(30 minutes), and rewarming. We compared surface, rectal temperature, and hemodynamic changes among passive, active, and maintenance phases, and esophageal histopathology against control. Compared with passive cooling, esophageal cooling achieved target Trectalsignificantly earlier (71.3 minutes vs. 17.25 minutes, p= 0.003) with significantly greater rates of reduction in rectal (p= 0.0002) and surface (p= 0.005) temperatures and heart rate (p= 0.04). A water temperature of 39.1°C–40.2°C at a flow of 108–120 mL/min maintained Trectalaround 35°C ± 0.2°C. The higher peak heart rate and blood pressure within 8 minutes of the maintenance phase (p= 0.04) subsequently stabilized. Histopathology showed congestion, edema, and neutrophil infiltration with increasing cycles. Esophageal cooling is feasible and effective in achieving rapid cooling in newborns. Subsequent maintenance at this temperature required continued circulation of warm water. Esophageal histopathology needs further evaluation after 72 hours servo-control cooling with a narrower range of water temperatures in a larger group of animals.

MYH9disorder is a rare autosomal dominant disease characterized by congenital thrombocytopenia with giant platelets and leukocyte inclusion bodies and is often associated with Alport-like symptoms, such as glomerulonephritis, sensorineural hearing loss, and cataracts. We report a Japanese pedigree wherein the MYH9p.R1165C mutation was present in over 4 generations. Three individuals were misdiagnosed as Bernard-Soulier syndrome carriers. Among the 12 patients with abnormal hematological features, the proband’s mother, aunt, and grandaunt presented with sensorineural hearing impairment, and the mother presented with presenile cataract, and nephritis. This case report confirms the previously established genotype-phenotype correlations of the MYH9disorder that p.R1165C is associated with variable expression of nonhematological manifestations. Careful detection of leukocyte inclusion bodies in peripheral blood smears is necessary to prevent misdiagnosis.

Moyamoya disease (MMD) is characterized by progressive stenosis and occlusion in the terminal portion of both internal carotid arteries (ICAs) and the formation of an abnormal vascular network. Because of the fragile structure of the collateral vessels, MMD is frequently accompanied by intracranial aneurysms that are mainly located within the abnormal basal network or the circle of Willis. However, the association between MMD and aneurysms of the ICAs has never been reported previously.

Background:Central venous access devices (CVADs) are essential in the modern management of patients with haematological malignancies and solid tumors. An often serious complication is catheter-associated bloodstream infection (CA-BSI) which is a major cause of morbidity and mortality. We have previously demonstrated (JHI 2011;78:26) in a retrospective study of 1127 CVADs that insertion of lines on the right side of the body was associated with increased risk of CA-BSI (HR 1.60, 95%CI 1.05-2.44). We hypothesized that this finding related to the predominance of right-handedness in the patient (as for the general) population, which may result in greater movement and thus associated bacterial contamination of the catheterised limb.