Epidemiology of Shoe Wearing Patterns Over Time in Older Women: Associations With Foot Pain and Hallux Valgus.

BACKGROUND: Foot problems are prevalent in older women and are thought to be associated with footwear. This study examined women's shoe wearing patterns over time and evaluated associations between footwear characteristics and foot pain and hallux valgus. METHODS: Women aged 50-89 years (n = 2,627) completed a survey that included drawings of four toe-box shapes and four heel heights. For each life decade, participants indicated which footwear style they wore most of the time. Foot pain in the past 12 months and hallux valgus were documented by self-report. Logistic regression examined associations between heel height, toe-box shape, foot pain and hallux valgus. RESULTS: Wearing shoes with a high heel and very narrow toe box between the ages of 20 and 29 was common, but decreased to less than 10% by the age of 40. Compared with women who had worn shoes with a very wide toe box, the likelihood of hallux valgus increased in those who had worn shoes with a wide (odds ratio [OR] 1.96, 95% CI 1.03-3.71), narrow (2.39, 1.29-4.42) and very narrow (2.70, 1.46-5.00) toe box between the ages of 20 and 29 and those who wore shoes with a very narrow toe box (1.93, 1.10-3.39) between the ages of 30 and 39. CONCLUSIONS: Women wear shoes with a lower heel and broader toe box as they age. Wearing constrictive footwear between the ages of 20 and 39 may be critical for developing hallux valgus in later life

Clinical significance of medial vs lateral compartment patellofemoral osteoarthritis: cross-sectional analyses in an adult population with knee pain

Objective To determine the comparative prevalence, associations with selected patient characteristics, and clinical outcomes of medial and lateral compartment patellofemoral (PF) joint osteoarthritis (OA). Methods Information was collected by questionnaires, clinical assessment, and radiographs from 745 eligible community‐dwelling symptomatic adults age ≥50 years. PF joint space narrowing (JSN) and osteophytes were scored from skyline radiographs using the Osteoarthritis Research Society International atlas. Multilevel models were used to assess associations of compartmental PF joint OA with age, sex, body mass index (BMI) and varus–valgus malalignment, while median regression was used to examine associations with clinical outcomes (current pain intensity on a numeric rating scale [0–10] and the function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index [0–68]). Results Isolated lateral PF joint OA was more common than isolated medial PF joint OA, particularly at higher severity thresholds. Irrespective of severity threshold, age (≥2 odds ratio [OR] 1.19 [95% confidence interval (95% CI) 1.12, 1.26]), BMI (≥2 OR 1.15 [95% CI 1.07, 1.24]), and valgus malalignment (≥2 OR 2.58 [95% CI 1.09, 6.07]) were associated with increased odds of isolated lateral JSN, but isolated medial JSN was only associated with age (≥2 OR 1.20 [95% CI 1.14, 1.27]). The pattern of association was less clear for PF joint osteophytes. Isolated lateral PF joint OA, defined by JSN or osteophytes, was associated with higher pain scores than isolated medial PF joint OA, but these differences were modest and were not significant. A similar pattern of association was seen for functional limitation but only when PF joint OA was defined by JSN. Conclusion Isolated lateral PF joint OA is more common than isolated medial PF joint OA, and it is more consistently associated with established OA risk factors. It is also associated with higher, but clinically nonsignificant, pain and function scores than isolated medial PF joint OA, particularly when PF joint OA is defined using JSN

Delineation of the frequency and boundary of chromosomal copy number variations in paediatric neuroblastoma

© 2018 Informa UK Limited, trading as Taylor & Francis Group. Neuroblastoma, the most common solid tumour in early childhood, is characterized by very frequent chromosomal copy number variations (CNVs). While chromosome 2p amplification, 17q gain, 1p and 11q deletion in human neuroblastoma tissues are well-known, the exact frequencies and boundaries of the chromosomal CNVs have not been delineated. We analysed the publicly available single nucleotide polymorphism (SNP) array data which were originally generated by the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative, defined the frequencies and boundaries of chromosomes 2p11.2–2p25.3 amplification, 17q11.1-17q25.3 gain, 1p13.3-1p36.33 deletion and 11q13.3-11q25 deletion in neuroblastoma tissues, and identified chromosome 7q14.1 (Chr7:38254795-38346971) and chromosome 14q11.2 (Chr14:21637401-22024617) deletion in blood and bone marrow samples from neuroblastoma patients, but not in tumour tissues. Kaplan Meier analysis showed that double deletion of Chr7q14.1 and Chr14q11.2 correlated with poor prognosis in MYCN gene amplified neuroblastoma patients. In conclusion, the oncogenes amplified or gained and tumour suppressor genes deleted within the boundaries of chromosomal CNVs in tumour tissues should be studied for their roles in tumourigenesis and as therapeutic targets. Focal deletions of Chr7q14.1 and Chr14q11.2 together in blood and bone marrow samples from neuroblastoma patients can be used as a marker for poorer prognosis and more aggressive therapies

Withaferin A activates TRIM16 for its anti-cancer activity in melanoma.

Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease

Kuiper belt analogues in nearby M-type planet-host systems

We present the results of a Herschel survey of 21 late-type stars that host planets discovered by the radial velocity technique. The aims were to discover new discs in these systems and to search for any correlation between planet presence and disc properties. In addition to the known disc around GJ 581, we report the discovery of two new discs, in the GJ 433 and GJ 649 systems. Our sample therefore yields a disc detection rate of 14 per cent, higher than the detection rate of 1.2 per cent among our control sample of DEBRIS M-type stars with 98 per cent confidence. Further analysis however shows that the disc sensitivity in the control sample is about a factor of two lower in fractional luminosity than for our survey, lowering the significance of any correlation between planet presence and disc brightness below 98 per cent. In terms of their specific architectures, the disc around GJ 433 lies at a radius somewhere between 1 and 30 au. The disc around GJ 649 lies somewhere between 6 and 30 au, but is marginally resolved and appears more consistent with an edge-on inclination. In both cases the discs probably lie well beyond where the known planets reside (0.06–1.1 au), but the lack of radial velocity sensitivity at larger separations allows for unseen Saturn–mass planets to orbit out to ~5 au, and more massive planets beyond 5 au. The layout of these M-type systems appears similar to Sun-like star + disc systems with low-mass planets.This work was supported by the European Union through ERC grant number 279973 (GMK & MCW)

The Compelling Case for Indentation as a Functional Exploratory and Characterization Tool

The utility of indentation testing for characterizing a wide range of mechanical properties of brittle materials is highlighted in light of recent articles questioning its validity, specifically in relation to the measurement of toughness. Contrary to assertion by some critics, indentation fracture theory is fundamentally founded in Griffith–Irwin fracture mechanics, based on model crack systems evolving within inhomogeneous but well-documented elastic and elastic–plastic contact stress fields. Notwithstanding some numerical uncertainty in associated stress intensity factor relations, the technique remains an unrivalled quick, convenient and economical means for comparative, site-specific toughness evaluation. Most importantly, indentation patterns are unique fingerprints of mechanical behavior and thereby afford a powerful functional tool for exploring the richness of material diversity. At the same time, it is cautioned that unconditional usage without due attention to the conformation of the indentation patterns can lead to overstated toughness values. Limitations of an alternative, more engineering approach to fracture evaluation, that of propagating a pre-crack through a 'standard' machined specimen, are also outlined. Misconceptions in the critical literature concerning the fundamental nature of crack equilibrium and stability within contact and other inhomogeneous stress fields are discussed.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/jace.1372

On the role of transverse motion in pseudo-steady gravity currents

Flow in the body of gravity currents is typically assumed to be statistically two-dimensional, and cross-stream flow is often neglected (Simpson 1997; Meiburg et al. 2015). Here, we assess the validity of such assumptions using Shake-the-Box particle tracking velocimetry measurements of experimental gravity current flows. The resulting instantaneous, volumetric, whole-field velocity measurements indicate that cross-stream and vertical velocities (and velocity fluctuations) are equivalent in magnitude and thus are key to energy distribution and dissipation within the flow. Further, the presented data highlight the limitations of basing conclusions regarding body structure on a single cross-stream plane (particularly if that plane is central). Spectral analysis and dynamic mode decomposition of the fully three-dimensional, volumetric velocity data suggests internal waves within the current body that are associated with coherent three-dimensional motions in higher Reynolds number flows. Additionally, a potential critical layer at the height of the downstream velocity maximum is identified

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis