Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies

Recording Lifetime Behavior and Movement in an Invertebrate Model

Characterization of lifetime behavioral changes is essential for understanding aging and aging-related diseases. However, such studies are scarce partly due to the lack of efficient tools. Here we describe and provide proof of concept for a stereo vision system that classifies and sequentially records at an extremely fine scale six different behaviors (resting, micro-movement, walking, flying, feeding and drinking) and the within-cage (3D) location of individual tephritid fruit flies by time-of-day throughout their lives. Using flies fed on two different diets, full sugar-yeast and sugar-only diets, we report for the first time their behavioral changes throughout their lives at a high resolution. We have found that the daily activity peaks at the age of 15–20 days and then gradually declines with age for flies on both diets. However, the overall daily activity is higher for flies on sugar-only diet than those on the full diet. Flies on sugar-only diet show a stronger diurnal localization pattern with higher preference to staying on the top of the cage during the period of light-off when compared to flies on the full diet. Clustering analyses of age-specific behavior patterns reveal three distinct young, middle-aged and old clusters for flies on each of the two diets. The middle-aged groups for flies on sugar-only diet consist of much younger age groups when compared to flies on full diet. This technology provides research opportunities for using a behavioral informatics approach for understanding different ways in which behavior, movement, and aging in model organisms are mutually affecting

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

A phase II study of weekly cisplatin, 6S-stereoisomer leucovorin and fluorouracil as first-line chemotherapy for elderly patients with advanced gastric cancer

The incidence of gastric cancer (GC) increases significantly after the fifth decade and palliative chemotherapy is the ultimate treatment in the majority of patients. We investigated safety and efficacy of a weekly regimen with cisplatin, fluorouracil and leucovorin as first-line chemotherapy for elderly patients with advanced GC. Chemotherapy-naive patients older than 65 years were considered eligible for study entry. Frail elderly patients were identified and excluded according to the following criteria: age >85 years, dependence in one or more activities of daily living (activities of daily living and instrumental activities of daily living scales), three or more comorbid conditions, one or more geriatric syndromes. Chemotherapy consisted of 1-day per week administration of intravenous cisplatin 35 mg m(-2), 6S-stereoisomer leucovorin 250 mg m(-2) and fluorouracil 500 mg m(-2) (PLF). Patients were re-evaluated after eight weekly cycles and six additional weekly administrations were planned for patients without disease progression. A 5-day subcutaneous filgrastim (5 mug Kg(-1) day(-1), days +1-+5) was used after the first treatment delay for neutropenia and maintained thereafter. In the whole group, the best intention-to-treat overall response rate was 43\% (95\% CI: 30-56\%). The time to disease progression and the median survival time were 5.3 and 8.6 months, respectively. Fatigue was the commonest nonhaematologic toxicity (71\% of the patients). Filgrastim was used in 30 patients who showed grade II (20 patients) or grade III (10 patients) neutropenia. Neither grade IV toxicity nor toxic deaths were observed. The weekly PLF regimen resulted safe and effective in elderly patients with advanced GC. This outpatient regimen is based on old and low-cost drugs and it may represent an alternative to new and more expensive combinations

Measuring Dysfunctional Attitudes in the General Population: The Dysfunctional Attitude Scale (form A) Revised

The Dysfunctional Attitude Scale (DAS) was designed to measure the intensity of dysfunctional attitudes, a hallmark feature of depression. Various exploratory factor analytic studies of the DAS form A (DAS-A) yielded mixed results. The current study was set up to compare the fit of various factor models. We used a large community sample (N = 8,960) to test the previously proposed factor models of the DAS-A using confirmatory factor analysis. The retained model of the DAS-A was subjected to reliability and validity analyses. All models showed good fit to the data. Finally, a two-factor solution of the DAS-A was retained, consisting of 17 items. The factors demonstrated good reliability and convergent construct validity. Significant associations were found with depression. Norm-scores were presented. We advocate the use of a 17-item DAS-A, which proved to be useful in measuring dysfunctional beliefs. On the basis of previous psychometric studies, our study provides solid evidence for a two-factor model of the DAS-A, consisting of ‘dependency’ and ‘perfectionism/performance evaluation’

Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta

Context: Placenta-derived circulating factors contribute to the maternal endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to be involved in vasculogenesis and endothelial repair. Low vitamin D concentrations are associated with an increased risk for preeclampsia. Objective: We hypothesized that the function of human fetal ECFCs in culture would be suppressed by exposure to preeclampsia-related factors-preeclampsia serum or hypoxic placental conditioned medium- in a fashion reversed by vitamin D. Design, Setting, Patients: ECFCs were isolated from cord blood of uncomplicated pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in explant culture were exposed to either 2% (hypoxic), 8% (normoxic) or 21% (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected. Outcome Measures: ECFC tubule formation (Matrigel assay) and migration were examined in the presence of either maternal serum from preeclampsia cases or uncomplicated pregnancy controls, or pooled CM, in the presence or absence of 1,25(OH)2 vitamin D3. Results: 1,25(OH)2 vitamin D3 reversed the adverse effects of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade, or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or VEGF blockade were partially prevented by vitamin D. Conclusion: Vitamin D promotes the capillary-like tubule formation and migration of ECFCs in culture, minimizing the negative effects of exposure to preeclampsia-related factors. Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia is warranted. © 2014 Brodowski et al

The Fate of Porous Hydroxyapatite Granules Used in Facial Skeletal Augmentation

Facial appearance is largely determined by the morphology of the underlying skeleton. Hydroxyapatite is one of several materials available to enhance projection of the facial skeleton. This study evaluated the long-term maintenance of augmented bony projection when porous hydroxyapatite granules are used on the facial skeleton. Ten female patients aged 28–58 years were studied following aesthetic augmentation of the facial skeleton at 24 sites using porous hydroxyapatite granules. Postoperative CT scans at 3 months served as the baseline measurement and compared with scans taken at 1 and 2 years, with the thickness of the hydroxyapatite measured in axial and coronal planes. Thickness of original bone plus overlay of hydroxyapatite, thickness of the overlying soft tissue, and the overall projection (bone plus soft tissue) were recorded. It was found that 99.7% of the hydroxyapatite was maintained at 2 years, with no statistical difference (t test) from the baseline measurement. The overall projection (bony and soft tissue) was maintained as there was no evidence of native bone resorption or soft tissue atrophy. Radiographic results confirmed that the use of porous hydroxyapatite granules for enhancement of the facial skeleton is not only a predictable procedure, but maintains full bony projection at 2 years

The Manipulative Complexity of Lower Paleolithic Stone Toolmaking

Early stone tools provide direct evidence of human cognitive and behavioral evolution that is otherwise unavailable. Proper interpretation of these data requires a robust interpretive framework linking archaeological evidence to specific behavioral and cognitive actions.Here we employ a data glove to record manual joint angles in a modern experimental toolmaker (the 4(th) author) replicating ancient tool forms in order to characterize and compare the manipulative complexity of two major Lower Paleolithic technologies (Oldowan and Acheulean). To this end we used a principled and general measure of behavioral complexity based on the statistics of joint movements.This allowed us to confirm that previously observed differences in brain activation associated with Oldowan versus Acheulean technologies reflect higher-level behavior organization rather than lower-level differences in manipulative complexity. This conclusion is consistent with a scenario in which the earliest stages of human technological evolution depended on novel perceptual-motor capacities (such as the control of joint stiffness) whereas later developments increasingly relied on enhanced mechanisms for cognitive control. This further suggests possible links between toolmaking and language evolution

COVID-19, systemic crisis, and possible implications for the wild meat trade in sub-Saharan Africa

Wild animals play an integral and complex role in the economies and ecologies of many countries across the globe, including those of West and Central Africa, the focus of this policy perspective. The trade in wild meat, and its role in diets, have been brought into focus as a consequence of discussions over the origins of COVID-19. As a result, there have been calls for the closure of China’s “wet markets”; greater scrutiny of the wildlife trade in general; and a spotlight has been placed on the potential risks posed by growing human populations and shrinking natural habitats for animal to human transmission of zoonotic diseases. However, to date there has been little attention given to what the consequences of the COVID-19 economic shock may be for the wildlife trade; the people who rely on it for their livelihoods; and the wildlife that is exploited. In this policy perspective, we argue that the links between the COVID-19 pandemic, rural livelihoods and wildlife are likely to be more complex, more nuanced, and more far-reaching, than is represented in the literature to date. We develop a causal model that tracks the likely implications for the wild meat trade of the systemic crisis triggered by COVID-19. We focus on the resulting economic shockwave, as manifested in the collapse in global demand for commodities such as oil, and international tourism services, and what this may mean for local African economies and livelihoods. We trace the shockwave through to the consequences for the use of, and demand for, wild meats as households respond to these changes. We suggest that understanding and predicting the complex dynamics of wild meat use requires increased collaboration between environmental and resource economics and the ecological and conservation sciences