Histomorphometric Assessment of Cancellous and Cortical Bone Material Distribution in the Proximal Humerus of Normal and Osteoporotic Individuals: Significantly Reduced Bone Stock in the Metaphyseal and Subcapital Regions of Osteoporotic Individuals

Osteoporosis is a systemic disorder predominantly affecting postmenopausal women but also men at an advanced age. Both genders may suffer from low-energy fractures of, for example, the proximal humerus when reduction of the bone stock or/and quality has occurred.The aim of the current study was to compare the amount of bone in typical fracture zones of the proximal humerus in osteoporotic and non-osteoporotic individuals.The amount of bone in the proximal humerus was determined histomorphometrically in frontal plane sections. The donor bones were allocated to normal and osteoporotic groups using the T-score from distal radius DXA measurements of the same extremities. The T-score evaluation was done according to WHO criteria. Regional thickness of the subchondral plate and the metaphyseal cortical bone were measured using interactive image analysis.At all measured locations the amount of cancellous bone was significantly lower in individuals from the osteoporotic group compared to the non-osteoporotic one. The osteoporotic group showed more significant differences between regions of the same bone than the non-osteoporotic group. In both groups the subchondral cancellous bone and the subchondral plate were least affected by bone loss. In contrast, the medial metaphyseal region in the osteoporotic group exhibited higher bone loss in comparison to the lateral side.This observation may explain prevailing fracture patterns, which frequently involve compression fractures and certainly has an influence on the stability of implants placed in this medial region. It should be considered when planning the anchoring of osteosynthesis materials in osteoporotic patients with fractures of the proximal humerus.     

红细胞保存期影响早产儿疗效的随机对照试验:研究设计

尽管目前趋于逐渐降低输血阅值,并开发技术避免输注异体血液,但异体红细胞输注仍是罹患疾病和贫血的新生儿重症监护患者一个重要的支持和挽救生命的方法.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Cortical parameters predict bone strength at the tibial diaphysis,but are underestimated by HR-pQCT and μCT compared to histomorphometry

Cortical bone and its microstructure are crucial for bone strength, especially at the long bone diaphysis. However, it is still not well-defined how imaging procedures can be used as predictive tools for mechanical bone properties. This study evaluated the capability of several high-resolution imaging techniques to capture cortical bone morphology and assessed the correlation with the bone's mechanical properties. The microstructural properties (cortical thickness [Ct.Th], porosity [Ct.Po], area [Ct.Ar]) of 11 female tibial diaphysis (40–90 years) were evaluated by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral-quantitative-computed-tomography (HR-pQCT), micro-CT (μCT) and histomorphometry. Stiffness and maximal torque to failure were determined by mechanical testing. T-Scores determined by DXA ranged from 0.6 to −5.6 and a lower T-Score was associated with a decrease in Ct.Th (p ≤ 0.001) while the Ct.Po (p ≤ 0.007) increased, and this relationship was independent of the imaging method. With decreasing T-Score, histology showed an increase in Ct.Po from the endosteal to the periosteal side (p = 0.001) and an exponential increase in the ratio of osteons at rest to those after remodelling. However, compared to histomorphometry, HR-pQCT and μCT underestimated Ct.Po and Ct.Th. A lower T-Score was also associated with significantly reduced stiffness (p = 0.031) and maximal torque (p = 0.006). Improving the accuracy of Ct.Po and Ct.Th did not improve prediction of the mechanical properties, which was most closely related to geometry (Ct.Ar). The ex-vivo evaluation of mechanical properties correlated with all imaging modalities, with Ct.Th and Ct.Po highly correlated with the T-Score of the tibial diaphysis. Cortical microstructural changes were underestimated with the lower resolution of HR-pQCT and μCT compared to the histological ‘gold standard’. The increased accuracy did not result in an improved prediction for local bone strength in this study, which however might be related to the limited number of specimens and thus needs to be evaluated in a larger collective.     

RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary

Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under‐described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild‐type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.