Relationship Between Structure and Mechanical Function of the Tissues of the Intervertebral Joint

This paper reviews our current understanding of the relationshipbetween the structures and properties of the tissues of thespine and their mechanical functions. Emphasis is on the humanlumbar spine. Vertebrae consist of a core of cancellous bone(low density) surrounded by a shell of cortical bone (high stiffness);as a result they have high stiffness but low mass. The intervertebraldisc is able to withstand compression because of the swellingpressure exerted by the nucleus pulposus which is constrained,radially, by the annulus fibrosus. Thus the disc acts as a thick-walledpressure vessel. Collagen fibers within the annulus providereinforcement during compression, bending and torsion of thedisc. Collagen fibers also provide tensile reinforcement andprevent tears spreading across ligaments. The ligamenta flavacontain elastic fibers (low stiffness and low strength) withcollagen fibers (high stiffness and high strength). In the unstretchedligamenta flava, the collagen fibers have almost random orientationsbut they become aligned as the ligament is stretched. This structureenables the high extensibility of elastic fibers to be exploitedbut protects them from damage at high strains. The structureof the interspinous ligament suggests that its main functionis to attach the thoracolumbar fascia to the posterior spine.Thus the fascia is maintained in tension when stretched by theabdominal muscles. This and other observations indicate theimportance of muscles for maintaining the stability of the spinalcolumn.     

Conformation of keratan sulphate

X-ray diffraction patterns from stretched films of keratan sulphate, isolated from bovine cornea, indicate that the molecules are twofold helices with an axial rise per disaccharide residue of 0.945 nm. These helices are oriented with their twofold screw axes parallel and about equally spaced, but are not further organized into regular crystalline arrays. Computer methods were used to construct a molecular model with the observed symmetry and axial rise per disaccharide residue, with standard bond lengths, bond angles and pyranose ring conformations and with a hydrogen bond of length 0.270 nm between O(3) of N-acetylglucosamine and O(5) of galactose. This model has no unacceptably short non-bonded interatomic distances. The intensity distribution of the diffraction pattern calculated from the co-ordinates of the model is in reasonable agreement with the observed intensity distribution. This keratan sulphate model is an extended polysaccharide chain fringed with charged sulphate side groups, and is similar to those that have already been reported for chondroitin sulphates and dermatan sulphate, paralleling the similarities in covalent structure and biological occurrence among these substances.     

Global health policies that support the use of banked donor human milk: a human rights issue

Background

The past ten years have witnessed a rising trend in the prevalence and duration of breastfeeding in Italy, but breastfeeding rates increase in an unequal way; they are higher in the North of Italy than in the South. The purpose of this study was to describe the experiences, expectations and beliefs of a sample of mothers, and to identify differences, if any, between the North and the South of Italy.

Methods

The study was conducted in two regions of Italy, Friuli Venezia Giulia in the Northeast and Basilicata in the South. Two hundred and seventy-nine mothers of infants and children 6 to 23 months of age were interviewed using an 85-item questionnaire including closed and open questions on infant feeding experiences and beliefs, sources of information and support, reasons for intended and actual choices and practices, and some demographic and social variables. Face-to-face interviews were conducted between May 2001 and September 2002. Quantitative and qualitative methods were used for data analysis.

Results

The distribution of the mothers by age, education, employment and parity did not differ from that of the general population of the two regions. The reported rates of initiation and duration of breastfeeding were also similar: 95% started breastfeeding, exclusive breastfeeding was 32% at three and 9% at six months, with 64% and 35% of any breastfeeding, respectively. Some differences were reported in the rates of full breastfeeding, reflecting different ages of introduction of non-nutritive fluids. These, as well as nutritive fluids – including infant formula – and complementary foods, were introduced far too early. Advice on infant feeding was generally provided by health professionals and often was not based on up-to-date recommendations. Mothers were generally aware of the advantages of breastfeeding, but at the same time reported problems that they were not able to solve alone or through social and health system support. Most mothers would welcome the support of a peer counsellor. More mothers in Basilicata than in Friuli Venezia Giulia reported difficulties with breastfeeding related to returning to work and were not familiar with their rights on breastfeeding and maternity leave.

Conclusion

Programmes for the protection, promotion and support of breastfeeding in these and similar regions of Italy should concentrate on better training of health professionals with regards to lactation management, communication, and counselling skills. The addition of trained peer counsellors could reinforce the work done by the health system and, through community involvement, could help change social prejudice in the mid- and long-term. The differences between regions should be taken into account in formulating these programmes to avoid increasing, and possibly to decrease, the current gaps.     

Molecular tilting in dried elastoidin and its implications for the structures of other collagen fibrils

Wet elastoidin spicules (fish fin rays) yield low-angle meridional X-ray diffraction patterns which resemble those from tendons. However, when the spicule dries the meridian splits into the arms of a diagonal cross (sometimes only one arm appears). Of the possible explanations we reject shearing of the axial arrangement of molecules but confirm tilting. We suggest that, in three dimensions, the molecules are tilted at angles which vary from 0 degrees at the centre to some maximum value at the surface of the spicule, resembling torsion of the array of molecules. Molecular tilting probably occurs in other collagen fibrils.     

Effect of removing the nucleus pulposus on the deformation of the annulus fibrosus during compression of the intervertebral disc

Eighteen frozen ovine discs were bisected, in the mid-sagittal plane, to produce 36 specimens. The cut surfaces were marked at the inner and outer annulus boundaries of the annulus fibrosus, both anteriorly and posteriorly, with Alcian blue stain. The sections were sealed by a transparent plate, and thawed. A compression of 1mm at a rate of 0.2mms(-1) was applied. The displacements of the Alcian blue marks were measured from the video images, recorded during the tests, using interactive image analysis software. Before removal of the nucleus, the inner boundaries of the annulus moved outwards during compression (P<0.001, anterior; P=0.01, posterior). However, after removal of the nucleus, both inner boundaries moved inwards (P<0.001, anterior and posterior). The outer boundaries moved outwards both before and after removal of the nucleus (P<0.001). The results showed that total removal of the nucleus changes the response of the annulus to compression.     

The regulation of mitochondrial DNA copy number in glioblastoma cells

As stem cells undergo differentiation, mitochondrial DNA (mtDNA) copy number is strictly regulated in order that specialized cells can generate appropriate levels of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to undertake their specific functions. It is not understood whether tumor-initiating cells regulate their mtDNA in a similar manner or whether mtDNA is essential for tumorigenesis. We show that human neural stem cells (hNSCs) increased their mtDNA content during differentiation in a process that was mediated by a synergistic relationship between the nuclear and mitochondrial genomes and results in increased respiratory capacity. Differentiating multipotent glioblastoma cells failed to match the expansion in mtDNA copy number, patterns of gene expression and increased respiratory capacity observed in hNSCs. Partial depletion of glioblastoma cell mtDNA rescued mtDNA replication events and enhanced cell differentiation. However, prolonged depletion resulted in impaired mtDNA replication, reduced proliferation and induced the expression of early developmental and pro-survival markers including POU class 5 homeobox 1 (OCT4) and sonic hedgehog (SHH). The transfer of glioblastoma cells depleted to varying degrees of their mtDNA content into immunocompromised mice resulted in tumors requiring significantly longer to form compared with non-depleted cells. The number of tumors formed and the time to tumor formation was relative to the degree of mtDNA depletion. The tumors derived from mtDNA depleted glioblastoma cells recovered their mtDNA copy number as part of the tumor formation process. These outcomes demonstrate the importance of mtDNA to the initiation and maintenance of tumorigenesis in glioblastoma multiforme.     

Development of a transient large strain contact method for biological heart valve simulations

A new 2D method to implement transient contact using Comsol Multiphysics (finite element analysis software that enables multiphysics simulations) is described, which is based on Hertzian contact. This method is compared to the existing (default) contact method that does not enable real transient simulations, but instead performs steady-state solutions where time is a constant. The two types of contact modelling have been applied to simple 2D biological heart valve models, undergoing strains in the region of 10% under 20 kPa pressure (applied over 0.3 s). Both the methods predicted comparable stress patterns, locations of peak stresses, deformations and directions of principal stress. The default contact method predicted slightly greater contact stresses, but spreads over a shorter surface length than the new contact method. The default contact method is useful for contact systems with little transient dependency, due to ease of use. However, where transient conditions are important the new contact method is preferred.