Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages

To assess possible differences between the mineral phases of cortical and cancellous bone, the structure and composition of isolated bovine mineral crystals from young (1–3 months) and old (4–5 years) postnatal bovine animals were analyzed by a variety of complementary techniques: chemical analyses, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and 31P solid-state magic angle spinning nuclear magnetic resonance spectroscopy (NMR). This combination of methods represents the most complete physicochemical characterization of cancellous and cortical bone mineral completed thus far. Spectra obtained from XRD, FTIR, and 31P NMR all confirmed that the mineral was calcium phosphate in the form of carbonated apatite; however, a crystal maturation process was evident between the young and old and between cancellous and cortical mineral crystals. Two-way analyses of variance showed larger increases of crystal size and Ca/P ratio for the cortical vs. cancellous bone of 1–3 month than the 4–5 year animals. The Ca/(P + CO3) remained nearly constant within a given bone type and in both bone types at 4–5 years. The carbonate and phosphate FTIR band ratios revealed a decrease of labile ions with age and in cortical, relative to cancellous, bone. Overall, the same aging or maturation trends were observed for young vs. old and cancellous vs. cortical. Based on the larger proportion of newly formed bone in cancellous bone relative to cortical bone, the major differences between the cancellous and cortical mineral crystals must be ascribed to differences in average age of the crystals

A simple, high-throughput, colourimetric, field applicable loop-mediated isothermal amplification (HtLAMP) assay for malaria elimination.

BACKGROUND: To detect all malaria infections in elimination settings sensitive, high throughput and field deployable diagnostic tools are required. Loop-mediated isothermal amplification (LAMP) represents a possible field-applicable molecular diagnostic tool. However, current LAMP platforms are limited by their capacity for high throughput. METHODS: A high-throughput LAMP (HtLAMP) platform amplifying mitochondrial targets using a 96-well microtitre plate platform, processing 85 samples and 11 controls, using hydroxynaphtholblue as a colourimetric indicator was optimized for the detection of malaria parasites. Objective confirmation of visually detectable colour change results was made using a spectrophotometer. A dilution series of laboratory-cultured 3D7 Plasmodium falciparum parasites was used to determine the limit of detection of the HtLAMP assay, using P. falciparum (HtLAMP-Pf) and Plasmodium genus (HtLAMP-Pg) primers, on whole blood and filter paper, and using different DNA extraction protocols. The diagnostic accuracy of HtLAMP was validated using clinical samples from Papua New Guinea, Malaysia, Ghana and The Gambia and its field applicability was evaluated in Kota Marudu district hospital, Sabah, Malaysia. RESULTS: The HtLAMP assay proved to be a simple method generating a visually-detectable blue and purple colour change that could be objectively confirmed in a spectrophotometer at a wavelength of 600 nm. When compared with PCR, overall HtLAMP-Pg had a sensitivity of 98 % (n = 260/266, 95 % CI 95-99) and specificity 83 % (n = 15/18, 95 % CI 59-96). HtLAMP-Pf had a sensitivity of 97 % (n = 124/128, 95 % CI 92-99) and specificity of 96 % (n = 151/157, 95 % CI 92-99). A validation study in a regional hospital laboratory demonstrated ease of performance and interpretation of the HtLAMP assay. HtLAMP-Pf performed in this field setting had a sensitivity of 100 % (n = 17/17, 95 % CI 80-100) and specificity of 95 % (n = 123/128, 95 % CI 90-98) compared with multiplex PCR. HtLAMP-Pf also performed well on filter paper samples from asymptomatic Ghanaian children with a sensitivity of 88 % (n = 23/25, 95 % CI 69-97). CONCLUSION: This colourimetric HtLAMP assay holds much promise as a field applicable molecular diagnostic tool for the purpose of malaria elimination

Recovery after spinal cord relapse in multiple sclerosis is predicted by radial diffusivity

Background: The aim of this study was to determine whether the diffusion tensor-derived radial diffusivity and axial diffusivity, measured in the cortico-spinal tract in the cervical cord, predict clinical recovery after a cord relapse in patients with multiple sclerosis, and change over time

Deoxygedunin, a Natural Product with Potent Neurotrophic Activity in Mice

Gedunin, a family of natural products from the Indian neem tree, possess a variety of biological activities. Here we report the discovery of deoxygedunin, which activates the mouse TrkB receptor and its downstream signaling cascades. Deoxygedunin is orally available and activates TrkB in mouse brain in a BDNF-independent way. Strikingly, it prevents the degeneration of vestibular ganglion in BDNF −/− pups. Moreover, deoxygedunin robustly protects rat neurons from cell death in a TrkB-dependent manner. Further, administration of deoxygedunin into mice displays potent neuroprotective, anti-depressant and learning enhancement effects, all of which are mediated by the TrkB receptor. Hence, deoxygedunin imitates BDNF's biological activities through activating TrkB, providing a powerful therapeutic tool for treatment of various neurological diseases

Investigating the influence of product perception and geometric features

Research in emotional design and Kansei Engineering has shown that aesthetics play a significant role in the appeal of a product. This paper contributes to establishing a methodology to identify the relationships between perceptions, aesthetic features, desire to own and background of consumers. Surveys were conducted with 71 participants to gather their perceptions of 11 vase concepts. Advanced statistical analyses, including mixed models, were applied to allow generalisation of the results beyond the data sample. Significant relations between the desire to own a product and how the product is perceived were found (the desire to own was found to be related to beautiful, expensive, elegant, exciting, feminine, common and dynamic vases), as well as between the perceptions and the parameters describing the form of the vases (a vase was perceived as beautiful if it had many curved lines and was simple and tall). An automated mixed model analysis was conducted and revealed that general rules can be found between aesthetic features, perceptions and ownership, which can apply across gender and culture. The findings include design rules that link aesthetic features with perceptions. These contribute to research as guidelines for design synthesis and can either be implemented via shape grammars or parametric modelling approaches. These rules are also interesting for 3D printing applications, especially important when the consumer is the designer. Some of these design rules are linked to the desire to own a product, they have implications for industry, and they offer guidelines to creating attractive products that people want to own

Gravitational Waves from Gravitational Collapse

Gravitational wave emission from the gravitational collapse of massive stars has been studied for more than three decades. Current state of the art numerical investigations of collapse include those that use progenitors with realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non--axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Expression Profiling Reveals Novel Hypoxic Biomarkers in Peripheral Blood of Adult Mice Exposed to Chronic Hypoxia

Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO) mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX), exposed for two weeks to normobaric chronic hypoxia (CH) or two weeks of CH followed by two weeks of normoxic recovery (REC). Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off), 230 genes were identified and separated into four distinct temporal categories. Class I) contained 1 transcript up-regulated in both CH and REC; Class II) contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III) contained 9 transcripts down-regulated both in CH and REC; Class IV) contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1) by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia

Oxytocin and cholecystokinin secretion in women with colectomy

BACKGROUND: Cholecystokinin (CCK) concentrations in plasma have been shown to be significantly higher in colectomised subjects compared to healthy controls. This has been ascribed to reduced inhibition of CCK release from colon. In an earlier study CCK in all but one woman who was colectomised, induced release of oxytocin, a peptide present throughout the gastrointestinal (GI) tract. The aim of this study was thus to examine if colectomised women had a different oxytocin response to CCK compared to healthy controls. METHODS: Eleven women, mean age 34.4 ± 2.3 years, who had undergone colectomy because of ulcerative colitis or constipation were studied. Eleven age-matched healthy women served as controls. All subjects were fasted overnight and given 0.2 μg/kg body weight of CCK-8 i.v. in the morning. Samples were taken ten minutes and immediately before the injection, and 10, 20, 30, 45, 60, 90 and 120 min afterwards. Plasma was collected for measurement of CCK and oxytocin concentrations. RESULTS: The basal oxytocin and CCK concentrations in plasma were similar in the two groups. Intravenous injection of CCK increased the release of oxytocin from 1.31 ± 0.12 and 1.64 ± 0.19 pmol/l to 2.82 ± 0.35 and 3.26 ± 0.50 pmol/l in controls and colectomised women, respectively (p < 0.001). Given the short half-life of CCK-8 in plasma, the increased concentration following injection could not be demonstrated in the controls. On the other hand, in colectomised women, an increase of CCK in plasma was observed for up to 20 minutes after the injection, concentrations increasing from 1.00 ± 0.21 to a maximum of 1.81 ± 0.26 pmol/l (p < 0.002). CONCLUSION: CCK stimulates the release of oxytocin in women. There is no difference in plasma concentrations between colectomised and controls. However, colectomy seems to reduce the metabolic clearance of CCK. The hyperCCKemia in patients who had undergone colectomy is consequently not only dependent on CCK release, but may also depend on reduced clearance