In vivo intrarater and interrater precision of measuring apparent bone mineral density in vertebral subregions using supine lateral dual-energy x-ray absorptiometry.

Analysis of apparent bone mineral density (BMD) in the lumbar spine is commonly based on anteroposterior (AP) scanning using dual-energy X-ray absorptiometry (DXA). Although not widely used, clinically important information can also be derived from lateral scanning. Vertebral bone density, and therefore strength, can may vary in different subregions of the vertebral body. Therefore, subregional BMD measurements might be informative about fracture risk. However, the intrarater and interrater precision of in vivo subregional BMD assessments from lateral DXA remains unknown. Ten normal, young (mean: 24 yr) and 10 older (mean: 63 yr) individuals with low BMD were scanned on one occasion using an AP/lateral sequence. Each lateral scan was reanalyzed six times at L2 by three raters to determine the intrarater and interrater precision in selecting seven regions of interest (subregions). Precision was expressed using percentage coefficients of variation (% CV) and intraclass correlation coefficients (ICC). Intrarater precision ranged from ICC(1,1) 0.971 to 0.996 (% CV: 0.50-3.68) for the young cohort and ICC(1,1) 0.934 to 0.993 (% CV: 1.46-5.30) for the older cohort. Interrater precision ranged from ICC(2,1) 0.804 to 0.915 (% CV: 1.11-2.35) for the young cohort and ICC(2,1) 0.912 to 0.984 (% CV: 1.85-4.32) for the older cohort. Scanning a subgroup of participants twice with repositioning was used to assess short-term in vivo precision. At L2, short-term in vivo precision ranged from ICC(1,1) 0.867 to 0.962 (% CV: 3.38-9.61), at L3 from ICC(1,1) 0.961 to 0.988 (% CV: 2.02-5.57) and using an L2/L3 combination from ICC(1,1) 0.942 to 0.980 (% CV: 2.04-4.61). This study demonstrated moderate to high precision for subregional analysis of apparent BMD in the lumbar spine using lateral DXA in vivo.     

Visual field deficits in cats reared with cyclodeviations of the eyes

Summary Visual fields of ten cats which had one or both eyes rotated at 8 days of age were measured by two forms of perimetry and compared to visual fields of two normal cats and of four cats with monocular rotations at 16 days, 3 months or 6 months of age. All animals showed excellent localization of visual stimuli and responded to the actual location of stimuli in space rather than to the retinal locus normally associated with that location. In cats with monocular rotations, the field of the normal eye was always normal, extending from 90 ° ipsilateral to 30 ° contralateral. Cats with rotations of one eye at 3 or 6 months of age had essentially normal fields in the rotated eye as well, while cats with surgery at 8 or 16 days had restricted horizontal fields. They responded only to stimuli in the ipsilateral hemifield; they were blind in the contralateral hemifield. Their superior and inferior visual fields were normal. The field deficits related consistently to visual field coordinates and not to the angle or direction of rotation. In cats with binocular rotations the visual field of at least one eye extended across the midline. Thus, the extent of the field depended upon sensorimotor experiences of the cat both before and after surgery. It is argued that these monocular field deficits have a central origin, not a retinal one.When tested with both eyes open, seven of 14 experimental animals did not respond throughout the visual field seen by each eye alone. The total visual field with both eyes open was less than the sum of the two monocular fields; greatest losses were most pronounced in the extreme periphery of the field ipsilateral to the rotated eye. Since changes in eye position (e.g., convergence during bincocular viewing) were not observed, it is suggested that the binocular losses indicate suppression of the deviated eye which has a central origin.All animals were tested for visual following, visually-triggered extension (placing), and visually-guided reaching. Cats which had been routinely encouraged to use the rotated eye(s) by occlusion of the other eye showed skilful performance within a few weeks after surgery as previously reported by Peck and Crewther (1975), Mitchell et al. (1976) and others. In contrast, two cats reared with both eyes open after unilateral rotation in infancy were profoundly handicapped, as previously reported by Yinon (1975, 1976).This research was supported by Grant NS 14116 from the US Public Health Service     

The Role of Diet in the Pathogenesis and Management of Inflammatory Bowel Disease: A Review

Inflammatory bowel diseases, which include ulcerative colitis and Crohn’s disease, are chronic relapsing and remitting inflammatory diseases of the gastrointestinal tract that are increasing in prevalence and incidence globally. They are associated with significant morbidity, reduced quality of life to individual sufferers and are an increasing burden on society through direct and indirect costs. Current treatment strategies rely on immunosuppression, which, while effective, is associated with adverse events. Epidemiological evidence suggests that diet impacts the risk of developing IBD and modulates disease activity. Using diet as a therapeutic option is attractive to patients and clinicians alike due to its availability, low cost and few side effects. Diet may influence IBD risk and disease behaviour through several mechanisms. Firstly, some components of the diet influence microbiota structure and function with downstream effects on immune activity. Secondly, dietary components act to alter the structure and permeability of the mucosal barrier, and lastly dietary elements may have direct interactions with components of the immune response. This review will summarise the mechanisms of diet–microbial–immune system interaction, outline key studies examining associations between diet and IBD and evidence demonstrating the impact of diet on disease control. Finally, this review will outline current prescribed dietary therapies for active CD.     

RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three‐dimensional nuclear organization of patient‐derived cell lines

PALB2/FANCN is a BRCA1‐ and BRCA2‐interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient‐derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q‐FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST‐1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild‐type FCLs generated from first‐degree relatives (P =1.04E‐10 and P =9.68E‐15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild‐type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2‐related cancers. © 2013 Wiley Periodicals, Inc.