Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that ...inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort. We find that A2M concentration in blood is significantly associated with CSF concentrations of the neuronal injury markers, tau and phosphorylated tau, and that higher baseline serum A2M concentration is associated with an almost threefold greater risk of progression to clinical symptoms of AD in men. These findings were replicated in the Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level approach combining large multi-tissue gene expression datasets with mass spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene network that includes regulator of calcineurin (RCAN1), an inhibitor of calcineurin, a well-characterized tau phosphatase. A2M gene and protein expression in the brain were significantly associated with gene and protein expression levels of calcineurin. Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.
Summary
What is known and objective
Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate. Inflammatory processes are involved in the pathogenesis ...of both brucellosis and depression. Therefore, we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis.
Methods
Forty outpatients with depression due to brucellosis with a Hamilton Depression Rating Scale score (HDRS) <19 participated in a randomized, double‐blind, placebo‐controlled trial and underwent 8 weeks of treatment with either celecoxib (200 mg bid) or placebo as an adjunctive to antibiotic therapy. Patients were evaluated using HDRS at baseline and weeks 4 and 8.
Result and discussion
Repeated‐measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score F (1·43, 57·41) = 37·22, P < 0·001. Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end 10 patients (50%) vs. no patient (0%), respectively, P < 0·001. No serious adverse event was observed.
What is new and conclusion
Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo.
This study shows celecoxib is a safe and effective modality for brucellosis‐induced depression when compared with placebo. In particular, celecoxib is associated with significantly faster improvement in depressive symptoms which makes this drug a potentially useful augmentative strategy in patients with depression due to brucellosis.
This is a clinical trial (phase 1).
The objective of this study was to asses the safety and feasibility of bone marrow mesenchymal stem cell (MSC) and Schwann cell (SC) co-injection through cerebral ...spinal fluid (CSF) for the treatment of patients with chronic spinal cord injury.
Six subjects with complete spinal cord injury due to trauma according to International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) developed by the American Spinal Injury Association were enrolled. They received autologous co-transplantation of MSC and SC through lumbar puncture. Neurological status of the patients was determined by ISNCSCI, as well as by assessment of functional status by Spinal Cord Independent Measure. Before and after cell transplantation, magnetic resonance imaging (MRI) was performed for all the patients. Before the procedure, all the patients underwent electromyography, urodynamic study (UDS) and MRI tractograghy. After transplantation, these assessments were performed in special cases when the patients reported any changes in motor function or any changes in urinary sensation.
Over the mean 30 months of follow-up, the radiological findings were unchanged without any evidence of neoplastic tissue overgrowth. American Spinal Injury Association class in one patient was changed from A to B, in addition to the improvement in indexes of UDS, especially bladder compliance, which was congruous with axonal regeneration detected in MRI tractography. No motor score improvement was observed among the patients.
No adverse findings were detected at a mean of 30 months after autologous transplantation of the combination of MSCs and SCs through CSF. It may suggest the safety of this combination of cells for spinal cord regeneration.
Three-dimensional computational models of the cerebrospinal fluid (CSF) flow and brain tissue are presented for evaluation of their hydrodynamic conditions before and after shunting for seven ...patients with non-communicating hydrocephalus. One healthy subject is also modeled to compare deviated patients data to normal conditions. The fluid-solid interaction simulation shows the CSF mean pressure and pressure amplitude (the superior index for evaluation of non-communicating hydrocephalus) in patients at a greater point than those in the healthy subject by 5.3 and 2 times, respectively.
The homotopy analysis method (HAM) is applied to study the behavior of a hyperbolic rods of quadrupole mass filter and a sinusoidal potential form V(ac) cos(Ωt). Numerical computation method of a ...20th-order HAM is employed to compare the physical properties of the confined ions with fifth-order Runge-Kutta method. Also, comparison is made for the first stability region, the ion trajectories in real time, the polar plots, and the ion trajectory in x-y plan. The results show that the two methods are fairly similar; therefore, the HAM method has potential application to solve linear and nonlinear equations of the charge particle confinement in quadrupole field.
Stochastic models have an important role in modeling and analyzing epidemic diseases for small size population. In this article, we study the generation of stochastic models for epidemic disease ...susceptible-infective-susceptible model. Here, we use the separation variable method to solve partial differential equation and the new developed modified probability generating function (PGF) of a random process to include a random catastrophe to solve the ordinary differential equations generated from partial differential equation. The results show that the probability function is too sensitive to
μ
,
β
and
γ
parameters.
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► Potential field distribution of a quadrupole mass filter with circular cross-section electrodes is described. ► Using superposition principle, we calculate potential around a round ...rod which is subjected to a given potential. ► By standard separation method, we obtain the potential distribution into the quadrupole mass filter with circular rods. ► Same equivalent operating point in two stability diagrams (having the same
β
y
) the associated modulated secular ion frequencies behavior are the same.
Potential field distribution of a quadrupole mass filter with circular cross-section electrodes is described. At first, using superposition principle, we calculate potential around a round rod which is subjected to a given potential. By standard separation method, we then able to obtain the potential distribution into the quadrupole mass filter with circular rods. The results are compared with those obtained with a conventional hyperbolic rod set. Also, the results show that, for the same equivalent operating point in two stability diagrams (having the same
β
y
) the associated modulated secular ion frequencies behavior are the same.
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