A pilot study to evaluate changes in pelvic floor muscle tone following pelvic organ prolapse surgery using a novel intra-vaginal pressure sensor device.

Introduction And Hypothesis: Pelvic floor muscle weakness is a common cause of pelvic organ prolapse and urinary incontinence. Surgical repair of prolapse is commonly undertaken; however, the impact on pelvic floor muscle tone is unknown. The aim of this study was to compare the effect of anterior and posterior colporrhaphy on pelvic floor activation.

Multiple origins of two Ochrosia (Apocynaceae) species endemic to the Bonin (Ogasawara) Islands.

The genus, Ochrosia, is widely distributed from the West Indian Ocean throughout tropical Asia to the Middle Southern Pacific region. Ochrosia comprises many island-endemic species, suggesting that long-distance dispersal and isolation after migration are key factors for clarifying the diversification process. However, the phylogeny and biogeography of endemic Ochrosia species have not been evaluated well due to the difficulty of adequate sampling from the entire distribution range of the genus.

Peri-ictal magnetic resonance imaging characteristics in dogs with suspected idiopathic epilepsy.

Background: The pathophysiology of changes in magnetic resonance imaging (MRI) detected after a seizure is not fully understood.

Objective: To characterize and describe seizure-induced changes detected by MRI.

Animals: Eighty-one client-owned dogs diagnosed with idiopathic epilepsy.

Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling.

Dissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into metastatic lesions are required. There is evidence that cancer stem cells (CSCs) within breast tumours are capable of metastasis, but the mechanism by which these colonise bone is unknown.

How stiff is skin?

The measurement of the mechanical properties of skin (such as stiffness, extensibility and strength) is a key step in characterisation of both dermal ageing and disease mechanisms and in the assessment of tissue-engineered skin replacements. However, the biomechanical terminology and plethora of mathematical analysis approaches can be daunting to those outside the field. As a consequence, mechanical studies are often inaccessible to a significant proportion of the intended audience.

Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin.

Lysyl oxidases (LOXs) play a central role in extracellular matrix remodeling during development and tumor growth and fibrosis through cross-linking of collagens and elastin. We have limited knowledge of the structure and substrate specificity of these secreted enzymes. LOXs share a conserved C-terminal catalytic domain but differ in their N-terminal region, which is composed of 4 repeats of scavenger receptor cysteine-rich (SRCR) domains in LOX-like (LOXL) 2.

Disrupted circadian clocks and altered tissue mechanics in primary human breast tumours.

Background: Circadian rhythms maintain tissue homeostasis during the 24-h day-night cycle. Cell-autonomous circadian clocks play fundamental roles in cell division, DNA damage responses and metabolism. Circadian disruptions have been proposed as a contributing factor for cancer initiation and progression, although definitive evidence for altered molecular circadian clocks in cancer is still lacking.

Accuracy of and interobserver agreement regarding thoracic computed tomography for the diagnosis of chronic bronchitis in dogs.

OBJECTIVE To characterize CT findings in dogs with a presumptive diagnosis of chronic bronchitis, estimate the accuracy of thoracic CT for the diagnosis of chronic bronchitis in dogs, and determine interobserver agreement for this method. DESIGN Retrospective case-control and cross-sectional study. ANIMALS 26 dogs with confirmed chronic bronchitis and 20 control dogs with unremarkable results of thoracic CT and no recorded history of cough.

Macro- and micromechanical remodelling in the fish atrium is associated with regulation of collagen 1 alpha 3 chain expression.

Numerous pathologies lead to remodelling of the mammalian ventricle, often associated with fibrosis. Recent work in fish has shown that fibrotic remodelling of the ventricle is 'reversible', changing seasonally as temperature-induced changes in blood viscosity alter haemodynamic load on the heart. The atrial response to varying haemodynamic load is less understood in mammals and completely unexplored in non-mammalian vertebrates.

Agreement between transverse T2-weighted and three-dimensional constructive interference in steady state sequences in the evaluation of spinal cord disease in dogs.

The constructive interference in steady state (CISS) sequence has been widely used in human neuroimaging. It has been shown to be advantageous in the evaluation of intra-axial and extra-axial cystic abnormalities, arteriovenous and dysraphic malformations and disturbances of cerebrospinal fluid circulation. To assess the utility of this technique in small animals, interpretations based on this sequence were compared with those based on T2-weighted (T2W) sequences in 145 dogs that underwent MRI of the spine for suspected spinal cord disease.

Late-onset recurrence of neurological deficits after surgery for spinal arachnoid diverticula.

Spinal cord dysfunction secondary to spinal arachnoid diverticula (SAD) has been widely reported in the veterinary literature and there is some suggestion that surgical treatment may provide better outcomes than medical treatment. Despite this, previous reports have mentioned cases with recurrence of clinical signs following surgical treatment but the cause for this has not been further investigated. The medical records of seven dogs and one cat which presented for investigation of recurrence of neurological deficits at least six months after surgery for SAD were retrospectively reviewed.

Cellular mechano-environment regulates the mammary circadian clock.

Circadian clocks drive ∼24 h rhythms in tissue physiology. They rely on transcriptional/translational feedback loops driven by interacting networks of clock complexes. However, little is known about how cell-intrinsic circadian clocks sense and respond to their microenvironment.

Raised mammographic density: causative mechanisms and biological consequences.

High mammographic density is the most important risk factor for breast cancer, after ageing. However, the composition, architecture, and mechanical properties of high X-ray density soft tissues, and the causative mechanisms resulting in different mammographic densities, are not well described. Moreover, it is not known how high breast density leads to increased susceptibility for cancer, or the extent to which it causes the genomic changes that characterise the disease.

The Dynamic Nature of Hypertrophic and Fibrotic Remodeling of the Fish Ventricle.

Chronic pressure or volume overload can cause the vertebrate heart to remodel. The hearts of fish remodel in response to seasonal temperature change. Here we focus on the passive properties of the fish heart.

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density.

Background: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins.

ANATOMICAL STUDY OF CRANIAL NERVE EMERGENCE AND SKULL FORAMINA IN THE HORSE USING MAGNETIC RESONANCE IMAGING AND COMPUTED TOMOGRAPHY.

For accurate interpretation of magnetic resonance (MR) images of the equine brain, knowledge of the normal cross-sectional anatomy of the brain and associated structures (such as the cranial nerves) is essential. The purpose of this prospective cadaver study was to describe and compare MRI and computed tomography (CT) anatomy of cranial nerves' origins and associated skull foramina in a sample of five horses. All horses were presented for euthanasia for reasons unrelated to the head.

Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition, and micromechanical properties of nucleus pulposus constructs.

Introduction: Currently, there is huge research focus on the development of novel cell-based regeneration and tissue-engineering therapies for the treatment of intervertebral disc degeneration and the associated back pain. Both bone marrow-derived (BM) mesenchymal stem cells (MSCs) and adipose-derived MSCs (AD-MSCs) are proposed as suitable cells for such therapies. However, currently no consensus exists as to the optimum growth factor needed to drive differentiation to a nucleus pulposus (NP)-like phenotype.

Trephination of the frontal sinuses and instillation of clotrimazole cream: a computed tomographic study in canine cadavers.

Objective: To use computed tomography (CT) to assess the distribution of surgically administered clotrimazole cream and associated filling of the frontal sinuses and caudal aspect of the nasal cavities in canine cadavers.

Study Design: Observational study.

Animals: Small (n = 1) and medium-large (n = 11) breed canine cadavers.

New cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines.

The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH(2). Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N'-2- or N'-(4-chlorophenyl)piperazine moiety (IC(50) values range from 0.

Bioinformatic selection of putative epigenetically regulated loci associated with obesity using gene expression data.

There is considerable interest in defining the relationship between epigenetic variation and the risk of common complex diseases. Strategies which assist in the prioritisation of target loci that have the potential to be epigenetically regulated might provide a useful approach in identifying concrete examples of epigenotype-phenotype associations. Focusing on the postulated role of epigenetic factors in the aetiopathogenesis of obesity this report outlines an approach utilising gene expression data and a suite of bioinformatic tools to prioritise a list of target candidate genes for more detailed experimental scrutiny.

Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles.

Background: Patterns of DNA methylation change with age and these changes are believed to be associated with the development of common complex diseases. The hypothesis that Long Interspersed Nucleotide Element 1 (LINE-1) DNA methylation (an index of global DNA methylation) is associated with biomarkers of metabolic health was investigated in this study.

Methods: Global LINE-1 DNA methylation was quantified by pyrosequencing in blood-derived DNA samples from 228 individuals, aged 49-51 years, from the Newcastle Thousand Families Study (NTFS).

Effects of body position, imaging plane, and observer on computed tomographic measurements of the lumbosacral intervertebral foraminal area in dogs.

Objective: To evaluate effects of imaging plane, flexion and extension, patient weight, and observer on computed tomographic (CT) image measurements of the area of the lumbosacral (L7-S1) intervertebral foramen (LSIF) in dogs.

Sample: 12 dog cadavers (2 were excluded because of foraminal stenosis).

Procedures: In each cadaver, sagittal, sagittal oblique, transverse oblique, and double oblique CT images were obtained at 3 zones (entrance, middle, and exit zones) of the region of the lateral lumbar spinal canal that comprises the LSIF while the lumbosacral junction (LSJ) was positioned in flexion or extension.

Eosinophilic fibrosing gastritis and toxoplasmosis in a cat.

A 3-year-old, neutered male Tiffany cat was presented to the Animal Health Trust for investigation of pyrexia and a gastric lesion. Radiography and ultrasound showed severe thickening of the gastric wall and regional lymphadenopathy. There was altered gastric wall layering, predominately due to muscularis thickening.

Acquisition and extinction of conditioned nicotine analgesic tolerance.

These studies demonstrated the acquisition and extinction of conditioned tolerance to the analgesic effect of nicotine in rats. In Experiment 1, distinctive environmental cues were either paired or unpaired with nicotine. Following acquisition, the paired group was more tolerant to nicotine than the unpaired and saline groups.