The vertebral venous system in healthy and scoliotic adolescent spines - a 3D MRI investigation

Introduction. The venous drainage system within vertebral bodies (VBs) has been well documented previously in cadaveric specimens. Advances in 3D imaging and image processing now allow for in vivo quantification of larger venous vessels, such as the basivertebral vein. Differences between healthy and scoliotic VB veins can therefore be investigated. Methods. 20 healthy adolescent controls and 21 AIS patients were recruited (with ethics approval) to undergo 3D MRI, using a 3 Tesla, T1-weighted 3D gradient echo sequence, resulting in 512 slices across the thoraco-lumbar spine, with a voxel size of 0.5x0.5x0.5mm. Using Amira Filament Editor, five transverse slices through the VB were examined simultaneously and the resulting observable vascular network traced. Each VB was assessed, and a vascular network recorded when observable. A local coordinate system was created in the centre of each VB and the vascular networks aligned to this. The length of the vascular network on the left and right sides (with a small central region) of the VB was calculated, and the spatial patterning of the networks assessed level-by-level within each subject. Results. An average of 6 (range 4-10) vascular networks, consistent with descriptions of the basivertebral vein, were identifiable within each subject, most commonly between T10-L1. Differences were seen in the left/right distribution of vessels in the control and AIS subjects. Healthy controls saw a percentage distribution of 29:18:53 across the left:centre:right regions respectively, whereas the AIS subjects had a slightly shifted distribution of 33:25:42. The control group showed consistent spatial patterning of the vascular networks across most levels, but this was not seen in the AIS group. Conclusion. Observation and quantification of the basivertebral vein in vivo is possible using 3D MRI. The AIS group lacked the spatial pattern repetition seen in the control group and minor differences were seen in the left/right distribution of vessels.

Multimodal imaging of the collagen and elastic fibre networks in the bovine intervertebral disc

INTRODUCTION. The intervertebral disc is the largest avascular structure in the human body, withstanding transient loads of up to nine times body weight during rigorous physical activity. The key structural elements of the disc are a gel-like nucleus pulposus surrounded by concentric lamellar rings containing criss-crossed collagen fibres. The disc also contains an elastic fiber network which has been suggested to play a structural role, but to date the relationship between the collagen and elastic fiber networks is unclear. CONCLUSION. The multimodal transmitted and reflected polarized light microscopy technique developed here allows clear differentiation between the collagen and elastic fiber networks of the intervertebral disc. The ability to image unstained specimens avoids concerns with uneven stain penetration or specificity of staining. In bovine tail discs, the elastic fiber network is intimately associated with the collagen network.

Brief report: Intestinal dysbiosis in ankylosing spondylitis

Objective Ankylosing spondylitis (AS) is a common, highly heritable immune-mediated arthropathy that occurs in genetically susceptible individuals exposed to an unknown but likely ubiquitous environmental trigger. There is a close relationship between the gut and spondyloarthritis, as exemplified in patients with reactive arthritis, in whom a typically self-limiting arthropathy follows either a gastrointestinal or urogenital infection. Microbial involvement in AS has been suggested; however, no definitive link has been established. The aim of this study was to determine whether the gut in patients with AS carries a distinct microbial signature compared with that in the gut of healthy control subjects. Methods Microbial profiles for terminal ileum biopsy specimens obtained from patients with recent-onset tumor necrosis factor antagonist-naive AS and from healthy control subjects were generated using culture-independent 16S ribosomal RNA gene sequencing and analysis techniques. Results Our results showed that the terminal ileum microbial communities in patients with AS differ significantly (P < 0.001) from those in healthy control subjects, driven by a higher abundance of 5 families of bacteria (Lachnospiraceae [P = 0.001], Ruminococcaceae [P = 0.012], Rikenellaceae [P = 0.004], Porphyromonadaceae [P = 0.001], and Bacteroidaceae [P = 0.001]) and a decrease in the abundance of 2 families of bacteria (Veillonellaceae [P = 0.01] and Prevotellaceae [P = 0.004]). Conclusion We show evidence for a discrete microbial signature in the terminal ileum of patients with AS compared with healthy control subjects. The microbial composition was demonstrated to correlate with disease status, and greater differences were observed between disease groups than within disease groups. These results are consistent with the hypothesis that genes associated with AS act, at least in part, through effects on the gut microbiome.

Ratcheting and wear behavior of Australian rail steel: Experimental investigation of material properties and sampling method

To The ratcheting behavior of high-strength rail steel (Australian Standard AS1085.1) is studied in this work for the purpose of predicting wear and damage to the rail surface. Historically, researchers have used circular test coupons obtained from the rail head to conduct cyclic load tests, but according to hardness profile data, considerable variation exists across the rail head section. For example, the induction-hardened rail (AS1085.1) shows high hardness (400-430 HV100) up to four-millimeters into the rail head’s surface, but then drops considerably beyond that. Given that cyclic test coupons five millimeters in diameter at the gauge area are usually taken from the rail sample, there is a high probability that the original surface properties of the rail do not apply across the entire test coupon and, therefore, data representing only average material properties are obtained. In the literature, disks (47 mm in diameter) for a twin-disk rolling contact test machine have been obtained directly from the rail sample and used to validate rolling contact fatigue wear models. The question arises: How accurate are such predictions? In this research paper, the effect of rail sampling position on the ratcheting behavior of AS1085.1 rail steel was investigated using rectangular shaped specimens. Uniaxial stress-controlled tests were conducted with samples obtained at four different depths to observe the ratcheting behaviour of each. Micro-hardness measurements of the test coupons were carried out to obtain a constitutive relationship to predict the effect of depth on the ratcheting behaviour of the rail material. This work ultimately assists the selection of valid material parameters for constitutive models in the study of rail surface ratcheting.

Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers

Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other pharmacologic interventions in a preclinical model of high MD.

Palissya: A global review and reassessment of Eastern Gondwanan material

The conifer genus Palissya is reviewed giving special attention to assessing the reliability of Gondwanan material referred to this genus. The collection localities of Australasian specimens are mapped on palaeogeographic reconstructions of Eastern Gondwana at relevant times between 179 Ma and 119 Ma. Australasian and other Gondwanan material previously referred to Palissya is considered to differ substantially from the generic diagnosis. Specimens from the Toarcian of Australasia are shown to be allied to Knezourocarpon; this genus is only known from the Toarcian of eastern Australia. Middle Jurassic–Lower Cretaceous Australasian specimens previously referred to Palissya are likely allied to the Knezourocarponaceae fam. nov. The higher taxonomic affinity of this family is unknown but broadly, its structure is suggestive of ginkgoalean or pteridospermous affiliation. Southern hemisphere specimens were probably catkin-like and megascopically very different from the northern hemisphere Palissya and the two groups are unlikely to be closely related. Consequently, genuine Palissya cones and foliage appear to be restricted to the Rhaetian–Lower Jurassic of the northern hemisphere.

Utility of temporal artery biopsy samples for genome-wide analysis of giant cell arteritis

Giant Cell Arteritis (GCA) is the most common vasculitis affecting the elderly. Archived formalin-fixed paraffin-embedded (FFPE) temporal artery biopsy (TAB) specimens potentially represent a valuable resource for large-scale genetic analysis of this disease. FFPE TAB samples were obtained from 12 patients with GCA. Extracted TAB DNA was assessed by real time PCR before restoration using the Illumina HD FFPE Restore Kit. Paired FFPE-blood samples were genotyped on the Illumina OmniExpress FFPE microarray. The FFPE samples that passed stringent quality control measures had a mean genotyping success of >97%. When compared with their matching peripheral blood DNA, the mean discordant heterozygote and homozygote single nucleotide polymorphisms calls were 0.0028 and 0.0003, respectively, which is within the accepted tolerance of reproducibility. This work demonstrates that it is possible to successfully obtain high-quality microarray-based genotypes FFPE TAB samples and that this data is similar to that obtained from peripheral blood.

Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis

Objective. The heritability of RA has been estimated to be ∼55%, of which the MHC contributes about one-third. HLA-DRB1 alleles are strongly associated with RA, but it is likely that significant non-DRB1 MHC genetic susceptibility factors are involved. Previously, we identified two three-marker haplotypes in a 106-kb region in the MHC class III region immediately centromeric to TNF, which are strongly associated with RA on HLA-DRB1*0404 haplotypes. In the present study, we aimed to refine these associations further using a combination of genotyping and gene expression studies. Methods. Thirty-nine nucleotide polymorphisms (SNPs) were genotyped in 95 DRB1*0404 carrying unrelated RA cases, 125 DRB1*0404 - carrying healthy controls and 87 parent-case trio RA families in which the affected child carried HLA-DRB1*04. Quantitative RT-PCR was used to assess the expression of the positional candidate MHC class III genes APOM, BAT2, BAT3, BAT4, BAT5, AIF1, C6orf47, CSNK2β and LY6G5C, and the housekeeper genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and β2-microglobulin (B2M) in 31 RA cases and 21 ethnically, age- and sex-matched healthy controls. Synovial membrane specimens from RA, PsA and OA cases were stained by an indirect immunoperoxidase technique using a mouse-anti-human AIF1 monoclonal antibody. Results. Association was observed between RA and single markers or two marker haplotypes involving AIF1, BAT3 and CSNK. AIF1 was also significantly overexpressed in RA mononuclear cells (1.5- to 1.9-fold difference, P = 0.02 vs HPRT, P = 0.002 vs B2M). AIF1 protein was clearly expressed by synovial macrophages in all the inflammatory synovial samples in contrast to the non-inflammatory OA samples. Conclusions. The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA.

Elevated temperature mechanical properties of hollow flange channel sections

The fire performance of cold-formed steel members is an important criterion to be verified for their successful use in structural applications. However, lack of clear design guidance on their fire performance has inhibited their usage in buildings. Their elevated temperature mechanical properties, i.e., yield strengths, elastic moduli and stress–strain relationships, are imperative for the fire design. In the past many researchers have proposed elevated temperature mechanical property reduction factors for cold-formed steels, however, large variations exist among them. The LiteSteel Beam (LSB), a hollow flange channel section, is manufactured by a combined cold-forming and electric resistance welding process. Its web, inner and outer flange elements have different yield strengths due to varying levels of cold-working caused by their manufacturing process. Elevated temperature mechanical properties of LSBs are not the same even within their cross-sections. Therefore an experimental study was undertaken to determine the elevated temperature mechanical properties of steel plate elements in LSBs. Elevated temperature tensile tests were performed on web, inner and outer flange specimens taken from LSBs, and their results are presented in this paper including their comparisons with previous studies. Based on the test results and the proposed values from previous studies and fire design standards, suitable predictive equations are proposed for the determination of elevated temperature mechanical properties of LSB web and flange elements. Suitable stress–strain models are also proposed for the plate elements of this cold-formed and welded hollow flange channel section.

Comparative in vitro and in vivo studies of enteric-coated pancrelipase preparations for pancreatic insufficiency

We evaluated three acid-resistant pancreatic enzyme preparations by in vitro assays, and by comparing degree of steatorrhea, creatorrhea, fecal wet weight, and stool energy losses in a randomized crossover study of patients with pancreatic insufficient cystic fibrosis. Aims of the study were to assess (a) the most practicable and reliable indicator of malabsorption; (b) the variation in enzyme batch potency; (c) the decline in enzyme batch potency with prolonged shelf life; and (d) the relative bio-efficacy of the different preparations. In the in vivo study, absorption of energy, nitrogen, and fat did not differ when comparing the three preparations at roughly pharmaceu-tically equivalent doses, but when expressed per capsule of pancreatic supplement ingested, absorption reflected relative enzyme content, favoring the higher potency preparations. Although steatorrhea was reasonably controlled by these preparations, stool energy losses varied from 800 to 1,100 kJ per day, suggesting greater attention be paid to overall energy absorption rather than absorption of individual nutrients. In addition, fecal energy loss correlated more closely with fecal wet weight (r = 0.81; p < 0.05) than with steatorrhea (r = 0.40; ns), such that 1 g wet feces = 8.37 kJ (± 0.14). In vitro enzyme potency varied markedly between batches of the same brand, and also a decline of up to 20% in amylase, lipase, and trypsin activity was noted over an 8-month period for each batch. Both observations have clinical implications at times of represcription. Finally, the higher potency preparations were more effective per capsule and reduced capsule dosage is therefore attainable. © 1993 Raven Press, Ltd., New York.

Study of Pinna nobilis growth from inner record: How biased are posterior adductor muscle scars estimates?

Previous studies have shown that the external growth records of the posterior adductor muscle scar (PAMS) of the bivalve Pinna nobilis are incomplete and do not produce accurate age estimations. We have developed a new methodology to study age and growth using the inner record of the PAMS, which avoids the necessity of costly in situ shell measurements or isotopic studies. Using the inner record we identified the positions of PAMS previously obscured by nacre and estimated the number of missing records in adult specimens with strong abrasion of the calcite layer in the anterior portion of the shell. The study of the PAMS and inner record of two shells that were 6 years old when collected showed that only 2 and 3 PAMS were observed, while 6 inner records could be counted, thus confirming our working methodology. Growth parameters of a P. nobilis population located in Moraira, Spain (western Mediterranean) were estimated with the new methodology and compared to those obtained using PAMS data and in situ measurements. For the comparisons, we applied different models considering the data alternatively as length-at-age (LA) and tag-recapture (TR). Among every method we tested to fit the Von Bertalanffy growth model, we observed that LA data from inner record fitted to the model using non-linear mixed effects and the estimation of missing records using the calcite width was the most appropriate. The equation obtained with this method, L = 573*(1 - e(-0.16(t-0.02))), is very similar to that calculated previously from in situ measurements for the same population.

Faecal incontinence in childhood : a multidisciplinary approach including biofeedback

One hundred and seven children with faecal incontinence were evaluated and managed over a 3 year period by a multidisciplinary team. After initial clinical assessment, evaluation of defaecatory mechanisms (using a balloon model) and assessment of personal-social development and self-concept were undertaken. Management was based on initial bowel evacuation, short-term laxatives, and habit training involving systematic use of positive reinforcement; 69 children received biofeedback conditioning. Idiopathic megacolon with constipation and soiling was the most common finding (98 cases). Other diagnoses included previously undiagnosed neurogenic bowel (three cases), post-surgical anal anomalies (four cases), and psychogenic encopresis (two cases). Idiopathic megacolon was characterized by decreased rectal sensation, increased threshold for external sphincter relaxation and an inability to evacuate. Faecal incontinence was associated with an undesirably low social self-concept (70% of the 40 evaluated), but was not related to a delay in development (mean general developmental quotient = 105 ± 8, for the 35 tested). Family psychopathology warranting referral for family therapy was found in 14 children (13%). The management programme yielded a short-term (3 months) cure rate of 68% and a long-term (12 months) cure rate of 90%, with 10% having continued soiling which varied from occasional to several incidents/week. No significant improvement in self-concept was observed overall, although marked improvements were observed in some children. We conclude that disordered defaecatory dynamics are a major determinant of faecal incontinence in children. Undesirably low social self-concepts but normal developmental ability accompany this condition. Management is facilitated by a multidisciplinary approach, acknowledging the role of both behavioural and physiological components of the problem. This approach is effective in eradicating soiling in the majority of cases, comparing favourably with other published data.

Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis

The efficacy, adverse reactions, and long-term effects of intestinal lavage treatment with a balanced electrolyte solution (Golytely) was evaluated in patients with cystic fibrosis and distal intestinal obstruction syndrome. Twenty-two patients with cystic fibrosis (mean age 21.8 years, range 14 to 34 years, 15 boys or men) who sough medical attention because of abdominal pain and a mass in the right iliac fossa received Golytely, 5.6 ± 1.9 L (mean ± 1 SD), either orally (n = 14) or via nasogastric tube (n = 8) during 5.6 ± 2.4 hours. No serious side effects occurred. Serum electrolyte values remained within normal limits. Body weight did not change significantly. Minor adverse reactions included bloating (n = 12), nausea (n = 8), vomiting (n = 1), and chills (n = 3). All but one patient reported impressive relief of symptoms and remained pain free for an average of 3 months (range 1 to 19 months). Symptoms of abdominal pain and radiologic signs of fecal impaction assessed before and after lavage both decreased significantly (P < .0001). During follow-up (mean 15.2 months, range 4 to 26 months), 11 patients required a total of 38 (range one to nine) additional doses of Golytely. Seven patients drank the solution at home (21 treatments); only two patients chose a nasogastric tube. In ten patients with symptoms of recurrent distal intestinal obstruction syndrome prior to institution of therapy, duration of hospitalization was significantly reduced by this treatment (5.1 ± 7.6 v 2.3 ± 6.3 hospital days per annum, P < .02). It is concluded that intestinal lavage is a well-accepted, safe, and effective therapy for distal intestinal obstruction syndrome in patients with cystic fibrosis.

Direct shear testing on unsaturated silty soils to investigate the effects of drying and wetting on shear strength parameters at low suction

A modified conventional direct shear device was used to measure unsaturated shear strength of two silty soils at low suction values (0 ~ 50 kPa) that were achieved by following drying and wetting paths of soil water characteristic curves (SWCCs). The results revealed that the internal friction angle of the soils was not significantly affected by either the suction or the drying wetting SWCCs. The apparent cohesion of soil increased with a decreasing rate as suction increased. Shear stress-shear displacement curves obtained from soil specimens subjected to the same net normal stress and different suction values showed a higher initial stiffness and a greater peak stress as suction increased. A soil in wetting exhibited slightly higher peak shear stress and more contractive volume change behavior than that of soil in drying at the same net normal stress and suction.

Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac diseases. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immunoreactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.