345 research outputs found

    High-mobility group box 1, an endogenous ligand of toll-like receptors 2 and 4, induces astroglial inflammation via nuclear factor kappa B pathway

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    Background: Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. In addition to its pathoge- nic ligands, toll-like receptors (TLRs) can be activated by damaged endogenous molecules that induce inflammatory signalling pathways such as high-mobility group box 1 protein (HMGB1).  Materials and methods: Using an ex-vivo rat optic nerve (RON) model, we sought to determine the effects of lipopolysaccharides (LPS; TLR4 agonist), zymosan (TLR2 agonist) or HMGB1 — with or without TLR2/4 antagonists, on the expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-ҡβ) for signalling pathway and astrocyte reactivity, using double immunohistochemistry; as well as on the modulation of the neurotoxicity. HMGB1-treated RON had significantly higher expression and co-localisation of GFAP and NF-ҡβ as compared to the un- treated control, which was a similar result to those treated with LPS and zymosan.  Results: Moreover, the HMGB1-induced inflammation was blocked by TLR2/4 antagonists (p = 0.05). However, the HMGB1-induced cell death was unblocked by TLR antagonists. Overall, HMGB1 endogenously mediates the signalling me- chanisms of neuroinflammation through TLR2/4.  Conclusions: Whereas, the neuronal death mechanism resulting from HMGB1 could be caused by a different signalling pathway. Gaining an understanding of these mechanisms may help researchers discover new therapeutic targets for neurodegenerative diseases.

    Pattern of Laboratory Parameters and Management of Secondary Hyperparathyroidism in Countries of Europe, Asia, the Middle East, and North America

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    Introduction This analysis explored laboratory mineral and bone disorder parameters and management of secondary hyperparathyroidism in patients undergoing hemodialysis in Belgium, Canada, China, France, Germany, Italy, Japan, Russia, Saudi Arabia, Spain, Sweden, the UK, and the USA. Methods Analyses used demographic, medication, and laboratory data collected in the prospective Dialysis Outcomes and Practice Patterns Study (2012\u20132015). The analysis included 20,612 patients in 543 facilities. Descriptive data are presented as regional mean (standard deviation), median (interquartile range), or prevalence, weighted for facility sampling fraction. No testing of statistical hypotheses was conducted. Results The frequency of serum intact parathyroid hormone levels\u2009>\u2009600 pg/mL was lowest in Japan (1%) and highest in Russia (30%) and Saudi Arabia (27%). The frequency of serum phosphorus levels\u2009>\u20097.0 mg/dL was lowest in France (4%), the UK (6%), and Spain (6%), and highest in China (27%). The frequency of serum calcium levels\u2009>\u200910.0 mg/dL was highest in the UK (14%) and China (13%) versus 2% to 9% elsewhere. Dialysate calcium concentrations of 2.5 mEq/mL were common in the USA (78%) and Canada (71%); concentrations of 3.0\u20133.5 mEq/L were almost universal at facilities in Italy, France, and Saudi Arabia (each 65\u200999%). Conclusions Wide international variation in mineral and bone disorder laboratory parameters and management practices related to secondary hyperparathyroidism suggests opportunities for optimizing care

    Aberrant right subclavian artery in a cadaver: a case report of an aortic arch anomaly

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    In early embryogenesis, aortic anomalies occur as a consequence of disorders in the development of the primitive aortic arches system. Aberrant right subclavian artery, also known as arteria lusoria, is one of the important congenital anomalies of the aortic arch, in which the right subclavian artery arises from the arch of aorta instead of the brachiocephalic trunk. During routine dissection of a female cadaver, we observed retro-oesophageal aberrant right subclavian artery arising as the fourth branch from the aortic arch. In this case, the brachiocephalic trunk was absent. Early detection of aortic arch anomalies through diagnostic interventions is helpful to avoid complications during surgical procedures

    Assessing the impact of climate conditions on the distribution of mosquito species in Qatar

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    Qatar is a peninsular country with predominantly hot and humid weather, with 88% of the total population being immigrants. As such, it leaves the country liable to the introduction and dissemination of vector-borne diseases, in part due to the presence of native arthropod vectors. Qatar's weather is expected to become warmer with the changing climatic conditions across the globe. Environmental factors such as humidity and temperature contribute to the breeding and distribution of different types of mosquito species in a given region. If proper and timely precautions are not taken, a high rate of particular mosquito species can result in the transmission of various vector-borne diseases. In this study, we analyzed the environmental impact on the probability of occurrence of different mosquito species collected from several different sites in Qatar. The Naive Bayes model was used to calculate the posterior probability for various mosquito species. Further, the resulting Naive Bayes predictions were used to define the favorable environmental circumstances for identified mosquito species. The findings of this study will help in the planning and implementation of an active surveillance system and preventive measures to curb the spread of mosquitoes in Qatar

    WDM for Multi-user Indoor VLC Systems with SCM

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    A system that employs wavelength division multiplexing (WDM) in conjunction with subcarrier multiplexing (SCM) tones is proposed to realize high data rate multi-user indoor visible light communication (VLC). The SCM tones, which are unmodulated signals, are used to identify each light unit, to find the optimum light unit for each user and to calculate the level of the co-channel interference (CCI). WDM is utilized to attain a high data rate for each user. In this paper, multicolour (four colours) laser diodes (LDs) are utilized as sources of lighting and data communication. One of the WDM colours is used to convey the SCM tones at the beginning of the connection to set up the connection among receivers and light units (to find the optimum light unit for each user). To evaluate the performance of our VLC system, we propose two types of receivers: an array of non-imaging receivers (NI-R) and an array of non-imaging angle diversity receivers (NI-ADR). In this paper, we consider the effects of diffuse reflections, CCI and mobility on the system performance

    Autosomal recessive long QT syndrome, type 1 in eight families from Saudi Arabia.

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    One of the most common primary cardiac arrhythmia syndromes is autosomal dominant long QT syndrome, type 1 (LQT1), chiefly caused by mono-allelic mutations in the javax.xml.bind.JAXBElement@1ece3341 gene. Bi-allelic mutations in the javax.xml.bind.JAXBElement@7269232c gene are causal to Jervell and Lange-Nielsen syndrome (JLNS), characterized by severe and early-onset arrhythmias with prolonged QTc interval on surface ECG and sensorineural deafness. Occasionally, bi-allelic mutations in javax.xml.bind.JAXBElement@2001e7dc are also found in patients without any deafness, referred to as autosomal recessive long QT syndrome, type 1 (AR LQT1). We used Sanger sequencing to detect the pathogenic mutations in javax.xml.bind.JAXBElement@4f6526ea gene in eight families from Saudi Arabia with autosomal recessive LQT1. We have detected pathogenic mutations in all eight families, two of the mutations are founder mutations, which are c.387-5T>A and p.Val172Met/p.Arg293Cys ( javax.xml.bind.JAXBElement@205e407c ). QTc and cardiac phenotype was found to be pronounced in all the probands comparable to the cardiac phenotype in JLNS patients. Heterozygous carriers for these mutations did not exhibit any clinical phenotype, but a significant number of them have sinus bradycardia. To the best of our knowledge, this is the first description of a large series of patients with familial autosomal recessive LQT, type 1. These mutations could be used for targeted screening in cardiac arrhythmia patients in Saudi Arabia and in people of Arabic ancestry

    Quality of Type 2 Diabetes Management in the States of The Co-Operation Council for the Arab States of the Gulf: A Systematic Review

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    Type 2 diabetes mellitus is a growing, worldwide public health concern. Recent growth has been particularly dramatic in the states of The Co-operation Council for the Arab States of the Gulf (GCC), and these and other developing economies are at particular risk. We aimed to systematically review the quality of control of type 2 diabetes in the GCC, and the nature and efficacy of interventions. We identified 27 published studies for review. Studies were identified by systematic database searches. Medline and Embase were searched separately (via Dialog and Ovid, respectively; 1950 to July 2010 (Medline), and 1947 to July 2010 (Embase)) on 15/07/2009. The search was updated on 08/07/2010. Terms such as diabetes mellitus, non-insulin-dependent, hyperglycemia, hypertension, hyperlipidemia and Gulf States were used. Our search also included scanning reference lists, contacting experts and hand-searching key journals. Studies were judged against pre-determined inclusion/exclusion criteria, and where suitable for inclusion, data extraction/quality assessment was achieved using a specifically-designed tool. All studies wherein glycaemic-, blood pressure- and/or lipid- control were investigated (clinical and/or process outcomes) were eligible for inclusion. No limitations on publication type, publication status, study design or language of publication were imposed. We found the extent of control to be sub-optimal and relatively poor. Assessment of the efficacy of interventions was difficult due to lack of data, but suggestive that more widespread and controlled trial of secondary prevention strategies may have beneficial outcomes. We found no record of audited implementation of primary preventative strategies and anticipate that controlled trial of such strategies would also be useful

    Investigation of material deformation mechanism in double side incremental sheet forming

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    Double side incremental forming (DSIF) is an emerging technology in incremental sheet forming (ISF) in recent years. By employing two forming tools at each side of the sheet, the DSIF process can provide additional process flexibility, comparing to the conventional single point incremental forming (SPIF) process, therefore to produce complex geometries without the need of using a backing plate or supporting die. Although this process has been proposed for years, there is only limited research on this process and there are still many unanswered open questions about this process. Using a newly developed ISF machine, the DSIF process is investigated in this work. Focusing on the fundamental aspects of material deformation and fracture mechanism, this paper aims to improve the understanding of the DSIF process. Two key process parameters considered in this study include the supporting force and relative position between master and slave tools. The material deformation, the final thickness distribution as well as the formability under varying conditions of these two process variables are investigated. An analytical model was developed to evaluate the stress state in the deformation zone. Using the developed model, an explicit relationship between the stress state and key process parameters was established and a drop of stress triaxiality was observed in the double contact zone, which explains the enhanced formability in the DSIF process. Based on the analytical and experimental investigation, the advancements and challenges of the DSIF process are discussed with a few conclusions drawn for future research

    A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

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    Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia
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