Internal jugular vein thrombosis in a warfarinised patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Internal jugular vein thrombosis (IJVT) is a rare but potentially fatal condition. It usually arises following trauma to the internal jugular vein but is also seen in association with coagulopathies and advanced malignancies as part of a para-neoplastic syndrome.</p> <p>Case presentation</p> <p>We report a case of a 44 year old woman with a strong past medical history and family history of thrombotic disease who presented with abdominal pain and ascites. A stage III ovarian carcinoma was diagnosed and she underwent debulking of the tumour. She sustained a peri-operative haemorrhage and required insertion of a central line into the right internal jugular vein. At one month follow-up she presented as an emergency with a left neck mass and painful swallowing. A duplex ultrasound of her neck identified a left IJVT to the level of the brachiocephalic vein which had occurred despite warfarinisation and an INR of greater than 2. She was commenced on intravenous heparin and the swelling resolved over the course of a week.</p> <p>Conclusion</p> <p>This case illustrates an unusual presentation of a rare condition. In this case, the precise aetiology is unclear as the IJVT may have been related to a coagulopathy or the presence of advanced malignancy and occurred despite adequate anticoagulation.</p

A study of prognostic factors in Chinese patients with diabetic foot ulcers

Objective: Few studies have identified factors as predictors of clinical prognosis of patients with diabetic foot ulcers (DFUs), especially of Chinese patients. In this study, we assessed the prognostic factors of Chinese patients with DFUs. Methods and materials: This was a retrospective study (January 2009–January 2011) of 194 DFUs conducted in an inpatient population at PLA 454 Hospital in Nanjing, China, to determine the prognostic influential factors of DFUs in Chinese patients. All of the studied patients were grouped into an amputation group, a non-healing group, and a cured group, according to the clinical prognosis. Patient parameters, including gender, age, smoking habits, education level, family history of diabetes mellitus, medical history, duration of foot lesions and complications, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), urinary albumin/creatinine ratio (Alb/Cr), fundus oculi, electrocardiogram, DFU characteristics, bacterial nature, and neuropathy, were cross-studied among the three groups. Results: Compared with the other two groups, the amputation group showed a higher number of males, older in age, lower ABI and TcPO2 levels, higher Wagner wound grading and size, and significantly higher urinary Alb/Cr ratio, blood urea nitrogen, serum creatinine, white blood cell count, and erythrocyte sedimentation rate. Compared to the cured group (162 patients), more patients with an older age, smoking, family history of diabetes mellitus, medical history of foot ulcerations, lower ABI and TcPO2 levels, higher urine Alb/Cr ratio, and serum creatinine were found in the non-healing group. Regression analysis was used to study the correlation between various factors and clinical prognosis, and the results were as follows: age, Wagner wound classification, and heel ulcerations were negatively correlated to the DFU prognosis, whereas the female population, ABI, and TcPO2 were positively correlated with DFU prognosis. Conclusion: In this retrospective study, we conclude that the DFU prognosis may be related to age, gender, wound location (heel), Wagner wound classification, ABI, and TcPO2 levels in the Chinese population

Signatures of magnetic separatrices at the borders of a crater flux transfer event connected to an active X‐line

In this paper, we present Magnetospheric Multiscale (MMS) observations of a flux transfer event (FTE) characterized by a clear signature in the magnetic field magnitude, which shows maximum at the center flanked by two depressions, detected during a period of stable southward interplanetary magnetic field. This class of FTEs are called “crater‐FTEs” and have been suggested to be connected with active reconnection X line. The MMS burst mode data allow the identification of intense fluctuations in the components of the electric field and electron velocity parallel to the magnetic field at the borders of the FTE, which are interpreted as signatures of the magnetic separatrices. In particular, the strong and persistent fluctuations of the parallel electron velocity at the borders of this crater‐FTE reported for the first time in this paper, sustain the field‐aligned current part of the Hall current system along the separatrix layer, and confirm that this FTE is connected with an active reconnection X line. Our observations suggest a stratification of particles inside the reconnection layer, where electrons are flowing toward the X line along the separatrix, are flowing away from the X line along the reconnected field lines adjacent to the separatrices, and more internally ions and electrons are flowing away from the X line with comparable velocities, forming the reconnection jets. This stratification of the reconnection layer forming the FTE, together with the reconnection jet at the trailing edge of the FTE, suggests clearly that this FTE is formed by the single X line generation mechanism

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Dopamine restores reward prediction errors in old age.

Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption - implications for osteoclast quality

<p>Abstract</p> <p>Background</p> <p>Normal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly have secondary effects on bone remodeling, a process which is of importance for the pathogenesis of both osteoporosis and osteoarthritis. We treated human osteoclasts with different inhibitors and characterized their resulting function.</p> <p>Methods</p> <p>Human CD14 + monocytes were differentiated into mature osteoclasts using RANKL and M-CSF. The osteoclasts were cultured on bone in the presence or absence of various inhibitors: Inhibitors of acidification (bafilomycin A1, diphyllin, ethoxyzolamide), inhibitors of proteolysis (E64, GM6001), or a bisphosphonate (ibandronate). Osteoclast numbers and bone resorption were monitored by measurements of TRACP activity, the release of calcium, CTX-I and ICTP, as well as by counting resorption pits.</p> <p>Results</p> <p>All inhibitors of acidification were equally potent with respect to inhibition of both organic and inorganic resorption. In contrast, inhibition of proteolysis by E64 potently reduced organic resorption, but only modestly suppressed inorganic resorption. GM6001 alone did not greatly affect bone resorption. However, when GM6001 and E64 were combined, a complete abrogation of organic bone resorption was observed, without a great effect on inorganic resorption. Ibandronate abrogated both organic and inorganic resorption at all concentrations tested [0.3-100 μM], however, this treatment dramatically reduced TRACP activity.</p> <p>Conclusions</p> <p>We present evidence highlighting important differences with respect to osteoclast function, when comparing the different types of osteoclast inhibitors. Each class of osteoclast inhibitors will lead to different alterations in osteoclast quality, which secondarily may lead to different bone qualities.</p

Discovery of novel GPVI receptor antagonists by structure-based repurposing.

Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin. Although effective, these drugs carry risks of increased bleeding and drug 'resistance', underpinning a drive for new antiplatelet agents. To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it. A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation. To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico. We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner. This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects. We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing