Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.

BackgroundTwo congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation.Hypothesis/objectivesPlatelet dysfunction in horses with this second thrombasthenia results from a secretory defect.AnimalsTwo affected and 6 clinically normal horses.MethodsEx vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1).ResultsPlatelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation.Conclusions and clinical significanceDefects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia

Carotid artery stenosis

Carotid endarterectomy is currently the most effective intervention to prevent stroke in patients with recent symptoms of carotid stenosis.1 2 It also prevents future stroke in younger patients (under 75 years) who have not yet had symptoms, as long as the risk of stroke and death from surgery is not more than 3% Patients naturally prefer carotid artery stenting to open surgery, but stenting has not been shown to be acceptably safe in clinical trials. Carotid endarterectomy has been in widespread use for more than 50 years, but carotid artery stenting is a more recent development. In the linked systematic review (doi:10.1136/bmj.c467), Meier and colleagues assessed the short term safety and intermediate term efficacy of carotid endarterectomy versus carotid artery stenting. They found that the short term (30 day) hazards of stroke and death after stenting in recent trials of symptomatic patients have improved but are not yet as good as those seen after surgery.5 In the intermediate term, the two treatments did not differ significantly for stroke or death (hazard ratio 0.90, 95% confidence interval 0.74 to 1.1).</p

Effect of dietary vitamin D3 supplementation on meat quality of naked neck chickens

Consumers’ interest of indigenous chicken meat is increasing. An experiment was conducted to determine the effect of vitamin D3 supplementation on meat quality of indigenous male naked neck chickens. Different supplementation levels of 0, 2000, 4000, 6000 and 8000 IU of vitamin D3 per kg DM of feed were used. 13 weeks old male naked neck chickens with a mean live weight of 1200 ± 3 g were supplemented with vitamin  D3 for a period of seven days before slaughter. A 2 (cooking or not) x 2 (postmortem agings of 0 or 24 hs) x 5 (vitamin D3 levels) factorial arrangement in a complete randomized design was used for shear force analysis of raw or cooked naked neck chicken meat. A 2 (postmortem agings of 0 or 24 hs) x 5 (vitamin D3 levels) factorial arrangement in a complete randomized design was used for sensory evaluation of the meat. A quadratic equation was used to determine vitamin D3 supplementation levels for optimum shear force value and sensory attributes. Vitamin D3 supplementation did not improve (P&gt;0.05) shear force values of unaged or aged raw and cooked naked neck chicken meat. Shear force values of unaged raw or cooked meat were optimized at different levels of 3735 (r2=0.832) and 2512 (r2=0.669) IU of vitamin D3 per kg DM feed, respectively. Shear force values of aged raw or cooked meat were optimized at different levels of 6728 (r2 =0.274) and 4249 (r2=0.873) IU of vitamin D3 per kg DM feed, respectively. Vitamin D3 supplementation had no effect (P&gt;0.05) on unaged meat tenderness, juiciness and flavour. However, vitamin D3 supplementation improved (P&lt;0.05) aged meat tenderness and flavour. Tenderness, juiciness and flavour of aged naked neck chicken meat were optimized at supplementation level of 6830 (r2=0.839), 6894 (r2=0.683) and 9795 (r2=0.657) IU of vitamin  D3 per kg DM. It was concluded that vitamin D3 supplementation improved tenderness and flavour of aged naked neck chicken meat. However, shear force values of unaged or aged raw or cooked naked neck chicken meat were not improved by vitamin D3 supplementation.Keywords: Shear force, postmortem aging, calpains, connective tissue, tenderness, juiciness, flavorAfrican Journal of Biotechnology Vol. 12(22), pp. 3576-358

Prognosis of carotid dissecting aneurysms: Results from CADISS and a systematic review.

OBJECTIVE: To determine the natural history of dissecting aneurysm (DA) and whether DA is associated with an increased recurrent stroke risk and whether type of antithrombotic drugs (antiplatelets vs anticoagulants) modifies the persistence or development of DA. METHODS: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy. Logistic regression was used to estimate age- and sex-adjusted odds ratios. We conducted a systematic review of published studies assessing the natural history of DA and stroke risk in patients with non-surgically-treated extracranial CAD with DA. RESULTS: In CADISS, DA was present in 24 of 264 patients at baseline. In 36 of 248 patients with follow-up neuroimaging at 3 months, 12 of the 24 baseline DAs persisted, and 24 new DA had developed. There was no association between treatment allocation (antiplatelets vs anticoagulants) and whether DA at baseline persisted at follow-up or whether new DA developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted odds ratio 0.84; 95% confidence interval 0.10-7.31; p = 0.88). Published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA. CONCLUSIONS: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered

A multiple scales approach to crack front waves

Perturbation of a propagating crack with a straight edge is solved using the method of matched asymptotic expansions (MAE). This provides a simplified analysis in which the inner and outer solutions are governed by distinct mechanics. The inner solution contains the explicit perturbation and is governed by a quasi-static equation. The outer solution determines the radiation of energy away from the tip, and requires solving dynamic equations in the unperturbed configuration. The outer and inner expansions are matched via the small parameter L/l defined by the disparate length scales: the crack perturbation length L and the outer length scale l associated with the loading. The method is first illustrated for a scalar crack model and then applied to the elastodynamic mode I problem. The dispersion relation for crack front waves is found by requiring that the energy release rate is unaltered under perturbation. The wave speed is calculated as a function of the nondimensional parameter kl where k is the crack front wavenumber, and dispersive properties of the crack front wave speed are described for the first time. The example problems considered here demonstrate that the potential of using MAE for moving boundary value problems with multiple scales.Comment: 25 pages, 5 figure

Sri Lankan tsunami refugees: a cross sectional study of the relationships between housing conditions and self-reported health

BACKGROUND: On the 26th December 2004 the Asian tsunami devastated the Sri Lankan coastline. More than two years later, over 14,500 families were still living in transitional shelters. This study compares the health of the internally displaced people (IDP), living in transitional camps with those in permanent housing projects provided by government and non-government organisations in Sri Lanka. METHODS: This study was conducted in seven transitional camps and five permanent housing projects in the south west of Sri Lanka. Using an interviewer-led questionnaire, data on the IDPs' self-reported health and housing conditions were collected from 154 participants from transitional camps and 147 participants from permanent housing projects. Simple tabulation with non-parametric tests and logistic regression were used to identify and analyse relationships between housing conditions and the reported prevalence of specific symptoms. RESULTS: Analysis showed that living conditions were significantly worse in transitional camps than in permanent housing projects for all factors investigated, except 'having a leaking roof'. Transitional camp participants scored significantly lower on self-perceived overall health scores than those living in housing projects. After controlling for gender, age and marital status, living in a transitional camp compared to a housing project was found to be a significant risk factor for the following symptoms; coughs OR: 3.53 (CI: 2.11-5.89), stomach ache 4.82 (2.19-10.82), headache 5.20 (3.09-8.76), general aches and pains 6.44 (3.67-11.33) and feeling generally unwell 2.28 (2.51-7.29). Within transitional camp data, the only condition shown to be a significant risk factor for any symptom was household population density, which increased the risk of stomach aches 1.40 (1.09-1.79) and headaches 1.33 (1.01-1.77). CONCLUSION: Internally displaced people living in transitional camps are a vulnerable population and specific interventions need to be targeted at this population to address the health inequalities that they report to be experiencing. Further studies need to be conducted to establish which aspects of their housing environment predispose them to poorer health

Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

The Online dating romance scam: The psychological impact on victims – both financial and non-financial

This paper examined the psychological impact of the online dating romance scam. Unlike other mass-marketing fraud victims, these victims experienced a ‘double hit’ of the scam: a financial loss and the loss of a relationship. For most, the loss of the relationship was more upsetting than their financial losses (many described the loss of the relationship as a ‘death’). Some described their experience as traumatic and all were affected negatively by the crime. Most victims had not found ways to cope given the lack of understanding from family and friends. Denial (e.g., not accepting the scam was real or not being able to separate the fake identity with the criminal) was identified as an ineffective means of coping, leaving the victim vulnerable to a second wave of the scam. Suggestions are made as to how to change policy with regards to law enforcement deal with this crime

Random walk with barriers: Diffusion restricted by permeable membranes

Restrictions to molecular motion by barriers (membranes) are ubiquitous in biological tissues, porous media and composite materials. A major challenge is to characterize the microstructure of a material or an organism nondestructively using a bulk transport measurement. Here we demonstrate how the long-range structural correlations introduced by permeable membranes give rise to distinct features of transport. We consider Brownian motion restricted by randomly placed and oriented permeable membranes and focus on the disorder-averaged diffusion propagator using a scattering approach. The renormalization group solution reveals a scaling behavior of the diffusion coefficient for large times, with a characteristically slow inverse square root time dependence. The predicted time dependence of the diffusion coefficient agrees well with Monte Carlo simulations in two dimensions. Our results can be used to identify permeable membranes as restrictions to transport in disordered materials and in biological tissues, and to quantify their permeability and surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde