The effects of textured insoles on quiet standing balance in four stance types with and without vision

Background: Wearing a textured shoe insole can decrease postural sway during static balance. Previous studies assessed bipedal and/or unipedal standing. In contrast, we aimed to investigate if textured insoles modulated postural sway during four stance types (bipedal, standard Romberg, tandem Romberg, and unipedal), with and without vision.Methods: The repeated measures design involved 28 healthy young adults (13 females; mean age = 26.86 +/- 6.6 yrs) performing quiet standing in the four stance types on a force platform, under two different insole conditions (textured insole; TI vs. smooth insole; SI), with eyes open and eyes closed. Postural sway was assessed via the range and standard deviation of the COP excursions in the anterior-posterior and medial-lateral sway, and overall mean velocity.Results: The main effect of insole type was statistically significant at the alpha p = 0.05 level (p = 0.045). Compared to smooth insoles, textured insoles reduced the standard deviation of anterior-posterior excursions (APSD). While simple main effect analyses revealed this was most pronounced during eyes closed bipedal standing, insole type did not provide a statistically significant interaction with either stance or vision in this measure, or any other. Postural sway showed statistically significant increases across both stance type (bipedal < standard Romberg < tandem Romberg < unipedal), and vision (eyes closed < eyes open), in almost all measures. Stance and vision did have a statistically significant interaction in each measure, reflecting greater postural disturbances with eyes closed when stance stability decreased.Conclusions: Overall, these results support textured insole use in healthy young adults to reduce postural sway measures. This is because APSD is an index of spatial variability, where a decrease is associated with improved balance and possibly translates to reduced falls risk. Placing a novel texture in the shoe presumably modulated somatosensory inputs. It is important to understand the underlying mechanisms by which textured insoles influence postural sway. As such, utilising a healthy adult group allows us to investigate possible mechanisms of textured insoles. Future research could investigate the potential underlying mechanisms of textured insole effects at a neuromuscular and cortical level, in healthy young adults

Investigating the dissociative subtype of post-traumatic stress disorder in single- and multi-event trauma-exposed youth: Prevalence, course, prognosis, severity and functional impairment

OBJECTIVES: This study aimed, following both single- and multi-event trauma, to ascertain prevalence and course of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in youth; how well early PTSD-DS predicts later PTSD; and whether dissociation accounts for unique variance in post-traumatic stress symptoms (PTSS) and functional impairment over and above the effect of other post-trauma cognitive processing factors and PTSS respectively. DESIGN AND METHODS: This study is a secondary analysis of data from the Acute Stress Programme for Children and Teenagers study (n = 234) and the Coping in Care After Trauma study (n = 110) in which children had experienced single- and multi-event trauma respectively. RESULTS: PTSD-DS diagnosis was common in children with PTSD regardless of trauma experienced (>39.0%). PTSD-DS showed a similar trajectory of natural recovery to PTSD, and it was similarly predictive of later PTSD following single-event trauma. Finally, dissociation was a significant factor in PTSS and functional impairment. CONCLUSIONS: These results should be viewed in the context of several limitations including narrow sample of participants which reduces the generalizability of results, concerns around children's ability to conceptualize challenging concepts such as dissociation and the use of self-report measures to form diagnostic groups. The PTSD-DS diagnosis may offer clinical utility to the extant PTSD diagnosis in children and adolescents, as dissociation has been shown to be a contributory factor in the maintenance of both PTSS and functional impairment. Further research is required to inform further editions of the DSM and other diagnostic systems

The effect of temperature on the stability of African swine fever virus BA71V isolate in environmental water samples

African swine fever virus (ASFV) is known to be very stable and can remain infectious over long periods of time especially at low temperatures and within different matrices, particularly those containing animal-derived organic material. However, there are some gaps in our knowledge pertaining to the survivability and infectivity of ASFV in groundwater. This study aims to determine the stability and infectivity of the cell culture-adapted ASFV strain BA71V by plaque assay after incubation of the virus within river water samples at three different environmentally relevant temperatures (4 °C, 15 °C, and 21 °C) over the course of 42 days. The results from this study indicate that ASFV can remain stable and infectious when maintained at 4 °C in river water for more than 42 days, but as incubation temperatures are increased, the stability is reduced, and the virus is no longer able to form plaques after 28 days and 14 days, respectively, when stored at 15 °C and 21 °C. Characterizing the survivability of ASFV in groundwater can allow us to develop more appropriate inactivation and disinfection methods to support disease control and mitigate ASFV outbreaks

Collecting Symptoms and Sensor Data With Consumer Smartwatches (the Knee OsteoArthritis, Linking Activity and Pain Study):Protocol for a Longitudinal, Observational Feasibility Study

BACKGROUND: The Knee OsteoArthritis, Linking Activity and Pain (KOALAP) study is the first to test the feasibility of using consumer-grade cellular smartwatches for health care research. OBJECTIVE: The overall aim was to investigate the feasibility of using consumer-grade cellular smartwatches as a novel tool to capture data on pain (multiple times a day) and physical activity (continuously) in patients with knee osteoarthritis. Additionally, KOALAP aimed to investigate smartwatch sensor data quality and assess whether engagement, acceptability, and user experience are sufficient for future large-scale observational and interventional studies. METHODS: A total of 26 participants with self-diagnosed knee osteoarthritis were recruited in September 2017. All participants were aged 50 years or over and either lived in or were willing to travel to the Greater Manchester area. Participants received a smartwatch (Huawei Watch 2) with a bespoke app that collected patient-reported outcomes via questionnaires and continuous watch sensor data. All data were collected daily for 90 days. Additional data were collected through interviews (at baseline and follow-up) and baseline and end-of-study questionnaires. This study underwent full review by the University of Manchester Research Ethics Committee (#0165) and University Information Governance (#IGRR000060). For qualitative data analysis, a system-level security policy was developed in collaboration with the University Information Governance Office. Additionally, the project underwent an internal review process at Google, including separate reviews of accessibility, product engineering, privacy, security, legal, and protection regulation compliance. RESULTS: Participants were recruited in September 2017. Data collection via the watches was completed in January 2018. Collection of qualitative data through patient interviews is still ongoing. Data analysis will commence when all data are collected; results are expected in 2019. CONCLUSIONS: KOALAP is the first health study to use consumer cellular smartwatches to collect self-reported symptoms alongside sensor data for musculoskeletal disorders. The results of this study will be used to inform the design of future mobile health studies. Results for feasibility and participant motivations will inform future researchers whether or under which conditions cellular smartwatches are a useful tool to collect patient-reported outcomes alongside passively measured patient behavior. The exploration of associations between self-reported symptoms at different moments will contribute to our understanding of whether it may be valuable to collect symptom data more frequently. Sensor data-quality measurements will indicate whether cellular smartwatch usage is feasible for obtaining sensor data. Methods for data-quality assessment and data-processing methods may be reusable, although generalizability to other clinical areas should be further investigated. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10238

Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood

The progressive aging of the world’s population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOE ε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson’s disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias

The PTTG1-binding factor (PBF/PTTG1IP) regulates p53 activity in thyroid cells

The PTTG1-Binding Factor (PBF/PTTG1IP) has an emerging repertoire of roles, especially in thyroid biology, and functions as a proto-oncogene. High PBF expression is independently associated with poor prognosis and lower disease-specific survival in human thyroid cancer. However, the precise role of PBF in thyroid tumorigenesis is unclear. Here, we present extensive evidence demonstrating that PBF is a novel regulator of p53, a tumor suppressor protein with a key role in maintaining genetic stability, which is infrequently mutated in differentiated thyroid cancer. By coimmunoprecipitation and proximity ligation assays, we show that PBF binds specifically to p53 in thyroid cells, and significantly represses transactivation of responsive promoters. Further, we identify that PBF decreases p53 stability by enhancing ubiquitination, which appears dependent on the E3 ligase activity of Mdm2. Impaired p53 function was evident in a transgenic mouse model with thyroid-specific PBF over-expression (PBF-Tg), which had significantly increased genetic instability as indicated by FISSR-PCR analysis. Consistent with this, ~40% of all DNA repair genes examined were repressed in PBF-Tg primary cultures, including genes with critical roles in maintaining genomic integrity such as Mgmt, Rad51 and Xrcc3. Our data also revealed that PBF induction resulted in upregulation of the E2 enzyme Rad6 in murine thyrocytes, and was associated with Rad6 expression in human thyroid tumors. Overall, this work provides novel insights into the role of the proto-oncogene PBF as a negative regulator of p53 function in thyroid tumorigenesis, where PBF is generally over-expressed and p53 mutations are rare compared to other tumor types

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

RUNX3 overexpression inhibits normal human erythroid development

RUNX proteins belong to a family of transcription factors essential for cellular proliferation, differentiation, and apoptosis with emerging data implicating RUNX3 in haematopoiesis and haematological malignancies. Here we show that RUNX3 plays an important regulatory role in normal human erythropoiesis. The impact of altering RUNX3 expression on erythropoiesis was determined by transducing human CD34+ cells with RUNX3 overexpression or shRNA knockdown vectors. Analysis of RUNX3 mRNA expression showed that RUNX3 levels decreased during erythropoiesis. Functionally, RUNX3 overexpression had a modest impact on early erythroid growth and development. However, in late-stage erythroid development, RUNX3 promoted growth and inhibited terminal differentiation with RUNX3 overexpressing cells exhibiting lower expression of glycophorin A, greater cell size and less differentiated morphology. These results suggest that suppression of RUNX3 is required for normal erythropoiesis. Overexpression of RUNX3 increased colony formation in liquid culture whilst, corresponding RUNX3 knockdown suppressed colony formation but otherwise had little impact. This study demonstrates that the downregulation of RUNX3 observed in normal human erythropoiesis is important in promoting the terminal stages of erythroid development and may further our understanding of the role of this transcription factor in haematological malignancies

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition