Composite bottlebrush mechanics: α-internexin fine-tunes neurofilament network properties.

Neuronal cytoplasmic intermediate filaments are principal structural and mechanical elements of the axon. Their expression during embryonic development follows a differential pattern, while their unregulated expression is correlated to neurodegenerative diseases. The largest neurofilament proteins of medium (NF-M) and high molecular weight (NF-H) were shown to modulate the axonal architecture and inter-filament spacing. However, the individual roles of the remaining α-internexin (α-Inx) and neurofilament of low molecular weight (NF-L) proteins in composite filaments remained elusive. In contrast to previous predictions, we show that when co-assembled with NF-M, the shortest and the least charged α-Inx protein increases inter-filament spacing. These findings suggest a novel structural explanation for the expression pattern of neurofilament proteins during embryonic development. We explain our results by an analysis of ionic cross-links between the disordered polyampholytic C-terminal tails and suggest that a collapsed conformation of the α-Inx tail domain interferes with tail cross-linking near the filament backbone.

A novel anchoring system for colonic stents: a pilot in vivo study in a porcine model.

BACKGROUND: Colorectal stents have a proven role in colorectal cancer as palliative care or a bridge to surgery. However, their efficacy and anchoring to the tissue varies according to stent design with stent migration rates up to 50 %. We present preliminary in vivo results of a new end-luminal anchoring system for stent fixation to the rectal canal. The aim was to assess the efficacy and safety of the stent using the anchoring system while subjecting the device to daily abdominal pressures related to daily activities in a porcine animal model. METHODS: Ex vivo anatomical and physical studies were performed to improve the system's structure and safety. Four female pigs were followed for the acute and chronic (16 weeks) period. Two animals were euthanized and underwent en-bloc pelvic visceral excision and histopathological examination. Device fixation time, animal behavior, device patency, anoscopic examination and histopathological features were assessed. RESULTS: Mean anchoring time was 13.83 weeks (standard error ± 1.38 weeks). One of the animals experienced early device expulsion with no complications. No obstruction was noted in any of the animals. Macroscopic examination revealed mild focal submucosal scarring in one animal and a normal examination in the other. Hematoxylin and eosin staining revealed mucosal ulceration and mixed inflammatory cell infiltrate, with no signs of granulomata, foreign body giant cell reaction or microabscess formation. CONCLUSIONS: A novel fixation device designed for long-term intrarectal implantation was well tolerated and maintained anal canal patency without migration. Larger studies are needed before its implementation in humans.

Characterization of a porcine model of post-operative pain.

BACKGROUND: Management of acute pain related to surgical intervention, termed post-operative pain or POP, continues to be a major healthcare challenge. While the rat plantar incision model provides valuable data to researchers about the mechanisms mediating POP, the development of topical and localized treatments in small animal models is limited. To help address these issues, we describe here the characterization of a large animal model of incisional pain. METHODS: Pigs underwent full-skin incision or full-skin and muscle incision and retraction (SMIR). Withdrawal thresholds were determined using the Von Frey test at baseline, 0.5-12 h post-surgery and on days 1, 2, 3, 5 and 7 post-surgery. The analgesic effects of systemic morphine [0.1 or 1.0 mg/kg intramuscular (i.m.) dose] and local anaesthetic ropivacaine were studied. Spontaneous pain-like behaviours were scored and analysed. The effects on wound healing were evaluated by gross observation and by histopathological examination. RESULTS: Pigs incurring SMIR demonstrated significantly increased mechanical hypersensitivity compared with pigs that underwent full-skin incision only (p < 0.05). Maximal analgesia was achieved with morphine (1 mg/kg i.m. dose) at 0.5 h post-treatment. Local treatment with ropivacaine was effective at increasing the withdrawal threshold to Von Frey filaments compared with saline control (p < 0.05) for a period of at least 6 h. Wounds healed normally with no signs of infection, redness or swelling. CONCLUSIONS: We propose that the pig model of incisional pain can provide an appropriate translational model for validating new topical and localized treatments for POP in humans.

Nuclear spectroscopy for in situ soil elemental analysis: Monte Carlo simulations.

We developed a model to simulate a novel inelastic neutron scattering (INS) system for in situ non-destructive analysis of soil using standard Monte Carlo Neutron Photon (MCNP5a) transport code. The volumes from which 90%, 95%, and 99% of the total signal are detected were estimated to be 0.23 m3, 0.37 m3, and 0.79 m3, respectively. Similarly, we assessed the instrument's sampling footprint and depths. In addition we discuss the impact of the carbon's depth distribution on sampled depth.

Gastric acid secretion in cold urticaria.

Four patients with cold urticaria and six control subjects were studied. Gastric acid output was measured for 1 hr before and 1 hr after the immersion of both hands in ice cold water. The mean acid output fell in the control group by 16.3%. Acid output in the cold urticaria patients rose in each case following the cold challenge. In three cases it rose by a mean of 52.6% and in one case by 1707%. Histamine is released locally and systemically during the reaction of cold urticaria. This is the most likely cause of the increase in gastric acid secretion.

D-xylose absorption test. Urine or blood?

The D-xylose absorption test has been used during the last four decades for evaluation of malabsorption in the small intestine. However, some disagreement still exists about the recommended method of performing this test: the 1-hr blood test, the 5-hr urine test, or both. We evaluated the test by performing 125 combined blood and urine tests in 111 patients. Normal xylose absorption was recorded in both blood and urine in 71 tests (group A, 56.8%). Abnormal test results in both blood and urine were recorded in 29 patients (group B, 23.2%). Only one patient had a pathological blood value and normal xylose excretion in the urine. Twenty-four patients (group D, 19.2%) had normal 1-hr blood xylose (greater than 25 mg/100 ml) with abnormal 5-hr urine xylose (less than 4.5 g/5 hr). Fat and/or bile salt malabsorption were documented in 21 patients (87.5%) of this group using stool fat analysis and the [14C]cholylglycine breath test. These data suggest that in adults the 5-hr urine collection more accurately reflects intestinal absorption in comparison with the 1-hr blood value.