The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation

Therapies directed against tumour necrosis factor (TNF) are effective for the treatment of rheumatoid arthritis and reduce pain scores in this condition. In this study, we sought to explore mechanisms by which TNF contributes to inflammatory pain in an experimental model of arthritis. The effects of an anti-TNF agent, etanercept, on behavioural pain responses arising from rat monoarthritis induced by complete Freund's adjuvant were assessed and compared with expression of TNF receptors (TNFRs) by dorsal root ganglion (DRG) cells at corresponding time points. Etanercept had no effect on evoked pain responses in normal animals but exerted a differential effect on the thermal and mechanical hyperalgesia associated with rat arthritis induced by complete Freund's adjuvant (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2 expression on DRG cells, which was maintained throughout the time course of the model. TNFR1 expression was increased in neuronal cells of the DRG bilaterally after arthritis induction. In contrast, TNFR2 expression occurred exclusively on nonneuronal cells of the macrophage-monocyte lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong correlation was observed between numbers of macrophages and the development of mechanical hyperalgesia in CFA-induced arthritis. These results highlight the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway

Radiological and clinical details of major adult limb fractures in a teaching hospital, AAU, Ethiopia

Background: This prospective study done at Addis Ababa University, Medical Faculty, Department of Radiology, Tikur Anbessa Hospital was aimed at determining the causes, magnitude, radiological and Clinical patterns of major limb fractures in adults in a half- year period from March to August 2007.In Addis Ababa University, fractures are managed both conservatively and operatively, but for lack of implants or expertise, patient which should have been treated surgically are managed conservatively and stay very long (average hospital stay of 11 days) in the Hospital. Such knowledge helps to plan on the management of the fractures and resource-recruitment. .Methods: This was a half-year cross-sectional higher institution based study of 422 adult patients with major fracture/s on the limbs. The study included all the major limb trauma patients who attended the 'surgical' and orthopedic Emergency department of T.A.U.H and had fracture at the same time. Data collection related to radiological variables was done by the research team to help reduce inter observer measurement variability. “Difficult” patterns were discussed further.Results: During the study period there were a total of 422 orthopedic adult patients who sustained a major fracture of their limbs. Mean age was 35 years with a male to female ratio was 3:1. Pathological fractures were encountered only in two (0.5%) patients. Nearly half (202, 48%) of the traumatic fractures were due to road traffic accidents. The highest frequency of fracture occurred on the femur (68, 15%), tibiofibular bones (63, 14%) and the humerus (61, 13.5%). A little less than half (44.1%) half of the femur fractures were in the proximal one-third and about half of the tibiofibular fractures were in the distal third. Transverse fracture pattern was seen in about half of the fractures. Compound fracture occurred in 90 (21.3%) of the cases. Thirty four (7.6) of the fractures involved the hand and only 13 (2.9%) involved the foot bones.Conclusion: The very high proportion of closed long bone shaft fractures in a center with limited number of beds compels short Hospital stay using efficient operative fixations, including SIGN interlocking nails, plates and other implants.. Road traffic accidents (RTAs) were responsible for almost half of the fractures. Machine injuries and fall injuries were second and third respectively. As the proportions and patterns of the leading causes of adult traumatic fractures remained steadily high over the many years (other similar studies published by the author on this journal), due mutisectorial attention should be emphasized once again to dwindle their burde

RNA editing of cytochrome c maturation transcripts is responsive to the energy status of leaf cells in Arabidopsis thaliana

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Minimizing the Cost of Team Exploration

A group of mobile agents is given a task to explore an edge-weighted graph $G$, i.e., every vertex of $G$ has to be visited by at least one agent. There is no centralized unit to coordinate their actions, but they can freely communicate with each other. The goal is to construct a deterministic strategy which allows agents to complete their task optimally. In this paper we are interested in a cost-optimal strategy, where the cost is understood as the total distance traversed by agents coupled with the cost of invoking them. Two graph classes are analyzed, rings and trees, in the off-line and on-line setting, i.e., when a structure of a graph is known and not known to agents in advance. We present algorithms that compute the optimal solutions for a given ring and tree of order $n$, in $O(n)$ time units. For rings in the on-line setting, we give the $2$-competitive algorithm and prove the lower bound of $3/2$ for the competitive ratio for any on-line strategy. For every strategy for trees in the on-line setting, we prove the competitive ratio to be no less than $2$, which can be achieved by the $DFS$ algorithm.Comment: 25 pages, 4 figures, 5 pseudo-code

Antihypertensive drug class and dyslipidemia: risk association among Chinese patients with uncomplicated hypertension

Factors associated with dyslipidemia in Chinese patients with uncomplicated hypertension were investigated in 1,139 patients newly prescribed a single antihypertensive drug in the public primary healthcare setting in Hong Kong, where their fasting lipid profiles were measured 4 to 16 weeks after the first prescription. Multivariate logistic regression showed that thiazide users were more likely (OR 3.67, 95% C.I. 1.13, 11.88, p=0.030) to have adverse (> 6.2mmol/l) total cholesterol (TC) compared with drugs acting on the renin angiotensin system (RAS), but the absolute difference in mean TC between thiazide users and all patients was small ( 0.14 mmol/l), while advanced age and male gender were also associated with some aspects of dyslipidemia. Clinicians should be aware of the increased risk of dyslipidemia in these groups, but the mild dyslipidemic profile associated with thiazides should not in itself deter its use as a possible first-line antihypertensive agent among Chinese patients

Approximation Algorithms for Generalized MST and TSP in Grid Clusters

We consider a special case of the generalized minimum spanning tree problem (GMST) and the generalized travelling salesman problem (GTSP) where we are given a set of points inside the integer grid (in Euclidean plane) where each grid cell is $1 \times 1$. In the MST version of the problem, the goal is to find a minimum tree that contains exactly one point from each non-empty grid cell (cluster). Similarly, in the TSP version of the problem, the goal is to find a minimum weight cycle containing one point from each non-empty grid cell. We give a $(1+4\sqrt{2}+\epsilon)$ and $(1.5+8\sqrt{2}+\epsilon)$-approximation algorithm for these two problems in the described setting, respectively. Our motivation is based on the problem posed in [7] for a constant approximation algorithm. The authors designed a PTAS for the more special case of the GMST where non-empty cells are connected end dense enough. However, their algorithm heavily relies on this connectivity restriction and is unpractical. Our results develop the topic further

Global small RNA analysis in fast-growing Arabidopsis thaliana with elevated concentrations of ATP and sugars

BACKGROUND: In higher eukaryotes, small RNAs play a role in regulating gene expression. Overexpression (OE) lines of Arabidopsis thaliana purple acid phosphatase 2 (AtPAP2) were shown to grow faster and exhibit higher ATP and sugar contents. Leaf microarray studies showed that many genes involved in microRNAs (miRNAs) and trans-acting siRNAs (tasiRNAs) biogenesis were significantly changed in the fast-growing lines. In this study, the sRNA profiles of the leaf and the root of 20-day-old plants were sequenced and the impacts of high energy status on sRNA expression were analyzed. RESULTS: 9-13 million reads from each library were mapped to genome. miRNAs, tasiRNAs and natural antisense transcripts-generated small interfering RNAs (natsiRNAs) were identified and compared between libraries. In the leaf of OE lines, 15 known miRNAs increased in abundance and 9 miRNAs decreased in abundance, whereas in the root of OE lines, 2 known miRNAs increased in abundance and 9 miRNAs decreased in abundance. miRNAs with increased abundance in the leaf and root samples of both OE lines (miR158b and miR172a/b) were predicted to target mRNAs coding for Dof zinc finger protein and Apetala 2 (AP2) proteins, respectively. Furthermore, a significant change in the miR173-tasiRNAs-PPR/TPR network was observed in the leaves of both OE lines. CONCLUSION: In this study, the impact of high energy content on the sRNA profiles of Arabidopsis is reported. While the abundance of many stress-induced miRNAs is unaltered, the abundance of some miRNAs related to plant growth and development (miR172 and miR319) is elevated in the fast-growing lines. An induction of miR173-tasiRNAs-PPR/TPR network was also observed in the OE lines. In contrast, only few cis- and trans-natsiRNAs are altered in the fast-growing lines.published_or_final_versio

Systematic characterization of novel lncRNAs responding to phosphate starvation in Arabidopsis thaliana

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Numerical modeling of the propagation environment in the atmospheric boundary layer over the Persian Gulf

Strong vertical gradients at the top of the atmospheric boundary layer affect the propagation of electromagnetic waves and can produce radar ducts. A three-dimensional, time-dependent, nonhydrostatic numerical model was used to simulate the propagation environment in the atmosphere over the Persian Gulf when aircraft observations of ducting had been made. A division of the observations into high- and low-wind cases was used as a framework for the simulations. Three sets of simulations were conducted with initial conditions of varying degrees of idealization and were compared with the observations taken in the Ship Antisubmarine Warfare Readiness/Effectiveness Measuring (SHAREM-115) program. The best results occurred with the initialization based on a sounding taken over the coast modified by the inclusion of data on low-level atmospheric conditions over the Gulf waters. The development of moist, cool, stable marine internal boundary layers (MIBL) in air flowing from land over the waters of the Gulf was simulated. The MIBLs were capped by temperature inversions and associated lapses of humidity and refractivity. The low-wind MIBL was shallower and the gradients at its top were sharper than in the high-wind case, in agreement with the observations. Because it is also forced by land–sea contrasts, a sea-breeze circulation frequently occurs in association with the MIBL. The size, location, and internal structure of the sea-breeze circulation were realistically simulated. The gradients of temperature and humidity that bound the MIBL cause perturbations in the refractivity distribution that, in turn, lead to trapping layers and ducts. The existence, location, and surface character of the ducts were well captured. Horizontal variations in duct characteristics due to the sea-breeze circulation were also evident. The simulations successfully distinguished between high- and low-wind occasions, a notable feature of the SHAREM-115 observations. The modeled magnitudes of duct depth and strength, although leaving scope for improvement, were most encouraging