Estimation of effective brain connectivity with dual Kalman filter and EEG source localization methods

Effective connectivity is one of the most important considerations in brain functional mapping via EEG. It demonstrates the effects of a particular active brain region on others. In this paper, a new method is proposed which is based on dual Kalman filter. In this method, firstly by using a brain active localization method (standardized low resolution brain electromagnetic tomography) and applying it to EEG signal, active regions are extracted, and appropriate time model (multivariate autoregressive model) is fitted to extracted brain active sources for evaluating the activity and time dependence between sources. Then, dual Kalman filter is used to estimate model parameters or effective connectivity between active regions. The advantage of this method is the estimation of different brain parts activity simultaneously with the calculation of effective connectivity between active regions. By combining dual Kalman filter with brain source localization methods, in addition to the connectivity estimation between parts, source activity is updated during the time. The proposed method performance has been evaluated firstly by applying it to simulated EEG signals with interacting connectivity simulation between active parts. Noisy simulated signals with different signal to noise ratios are used for evaluating method sensitivity to noise and comparing proposed method performance with other methods. Then the method is applied to real signals and the estimation error during a sweeping window is calculated. By comparing proposed method results in different simulation (simulated and real signals), proposed method gives acceptable results with least mean square error in noisy or real conditions.     

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003-2004)

Hypertension is a modifiable risk factor for cardiovascular disease, but its aetiology has not been fully elucidated. Recently, attention has been focused on the direct relations of plasma homocysteine (Hcy) to blood pressure (BP). The purpose of this study was to determine the relationship of Hcy with BP and other cardiovascular disease risk factors. This population-based study was a part of the Cardiovascular Risk Factors Survey and has been designed and conducted based on the methodology of the MONICA/WHO Project. A total of 1214 people aged 25-64 years were recruited using cluster sampling and assessed regarding standardized methods. BP was measured in seated position after a 10-min rest period. Blood samples were gathered and analysed according to standard methods. Variables were assessed in 1191 participants (416 men; 775 women). Mean age was higher in hypertensives compared to normotensives (P < 0.001). Mean Hcy was higher in hypertensives, but significant only in men (P < 0.031). Concurrent effects of Hcy, folate and vitamin B12 on hypertension indicated that Hcy acts as a risk factor and folate and vitamin B12 as protective factors; however, after adjustment, just vitamin B12 remained as a protective factor. Although we detected a simple correlation of Hcy with BP in Iranian adults, this relationship was no longer significant after applying an adjustment. In light of our observations, it is likely that the increased Hcy levels reported in hypertensive persons are concomitant rather than a precursor of hypertension.     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.     

Job satisfaction and the factors affecting satisfaction in nurse educators: A systematic review

Objectives

The present study seeks to answer the following two questions: Are nurse educators satisfied with their job? What are the factors affecting job satisfaction in nurse educators?

Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor

Background and Purpose

Cannabidiol has been reported to act as an antagonist at cannabinoid CB₁ receptors. We hypothesized that cannabidiol would inhibit cannabinoid agonist activity through negative allosteric modulation of CB₁ receptors.

Experimental Approach

Internalization of CB₁ receptors, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB₁ receptors and in the STHdh ^Q7/Q7 cell model of striatal neurons endogenously expressing CB₁ receptors. Cells were treated with 2‐arachidonylglycerol or Δ⁹‐tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol.

Key Results

Cannabidiol reduced the efficacy and potency of 2‐arachidonylglycerol and Δ⁹‐tetrahydrocannabinol on PLCβ3‐ and ERK1/2‐dependent signalling in cells heterologously (HEK 293A) or endogenously (STHdh ^Q7/Q7) expressing CB₁ receptors. By reducing arrestin2 recruitment to CB₁ receptors, cannabidiol treatment prevented internalization of these receptors. The allosteric activity of cannabidiol depended upon polar residues being present at positions 98 and 107 in the extracellular amino terminus of the CB₁ receptor.

Conclusions and Implications

Cannabidiol behaved as a non‐competitive negative allosteric modulator of CB₁ receptors. Allosteric modulation, in conjunction with effects not mediated by CB₁ receptors, may explain the in vivo effects of cannabidiol. Allosteric modulators of CB₁ receptors have the potential to treat CNS and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of these receptors.

Abbreviations

2‐AG

2‐arachidonyl glycerol

BRET_Eff

BRET efficiency

CBD

cannabidiol

FAAH

fatty acid amide hydrolase

NAM

negative allosteric modulator

THC

Δ⁹‐tetrahydrocannabinol

     

Effect of endurance training on retinol‐binding protein 4 gene expression and its protein level in adipose tissue and the liver in diabetic rats induced by a high‐fat diet and streptozotocin

Aims/Introduction

The present study was designed to investigate from which tissues the decrease in retinol‐binding protein 4 (RBP4) expression could contribute to the improvement of serum RBP4 and insulin resistance (IR) after endurance training.

Materials and Methods

Male 7‐week‐old Wistar rats were randomly assigned into four groups including control (C), trained (T), diabetic control (DC) and trained diabetic (TD). At 8 weeks‐of‐age, diabetes was induced by a high‐fat diet and intraperitoneal injection of low‐dose streptozotocin (STZ; 35 mg/kg). Rats in the T and TD groups carried out a 7‐week exercise program on a motorized treadmill (15–20 m/min for 20 min/day for 5 weeks), whereas the C and DC remained sedentary in their cages. Tissues gene expression and protein levels of RBP4 were assessed by using real‐time polymerase chain reaction and western blot, respectively, while serum RBP4 was measured using an enzyme‐linked immunosorbent assay kit.

Results

Exercise significantly improved IR and reduced serum concentration of RBP4 in the TD group. This reduction of serum RBP4 was accompanied by decreased RBP4 protein expression in visceral fat tissue. In contrast, exercise had no significant effect on RBP4 expression in liver and subcutaneous fat tissue in the TD group. Exercise also significantly decreased RBP4 gene expression in visceral fat tissue and muscle, whereas the effect of exercise on liver RBP4 messenger ribonucleic acid expression was not significant.

Conclusions

The present study showed that the mechanism for RBP4 reducing the effect of endurance training could involve decreased RBP4 messenger ribonucleic acid expression and its protein level in adipose tissue in STZ‐induced diabetic rats.     

Traumatic brain injury and adrenal insufficiency: morning cortisol and cosyntropin stimulation tests

Introduction

Adrenal insufficiency (AI) has a great impact on the prognosis of patients with traumatic brain injury. There is a lack of consensus regarding the diagnostic criteria of AI. In these patients with acute stress we compared fasting cortisol, low and high dose cosyntropin stimulation tests to assess adrenal function in patients with moderate to severe traumatic brain injury.

Material and methods

This multicenter, cross-sectional study recruited 50 consecutive patients (aged between 15 and 70 years old) with moderate to severe traumatic brain injury who survived more than 5 days after the event. The patients’ adrenal function was assessed using the fasting cortisol, 1 and 250-µg ACTH stimulation tests.

Results

More cases of AI were detected by the 1-µg ACTH stimulation test compared to those detected by the basal serum cortisol level and 250-µg ACTH stimulation test. The κ test showed no agreement between these tests. The incidence of AI in the first 10 days after traumatic brain injury varied from 34% to 82% according to the various definitions of AI. The incidence of hypotension and need for vasopressors was higher in the patients diagnosed by the 250-µg ACTH stimulation test (p < 0.0001).

Conclusions

The incidence of secondary AI in moderate to severe traumatic brain injury seems to be high. A combination of stimulation test (either 250 or 1 µg) and basal cortisol level may improve diagnostic ability compared to either test alone. Hence performing both tests for the assessment of adrenal function in patients with traumatic brain injury is recommended.     

Management of immune cytopenias in patients with systemic lupus erythematosus — Old and new

There are various immune cytopenias associated with systemic lupus erythematosus (SLE). The most common one is anemia; however, there are different etiologies for the anemia caused by SLE. Anemia could be due to chronic disease, secondary to renal insufficiency, blood loss, drug induced or autoimmune hemolysis. There are other very rare causes of anemia secondary to SLE which include red cell aplasia, aplastic anemia, and microangiopathic hemolytic anemia. Treatment of the anemia would be according to the cause. Leukopenia, neutropenia, and lymphopenia are hematologic complications associated with SLE, and in majority of cases no treatment is required. Thrombocytopenia is one of the complications of SLE and is usually treated by steroids. However, there are significant numbers of patients which will either not respond to or relapse after treatment. This article summarizes immune cytopenias seen in patients with SLE, and it also discusses management of these cytopenias.     

SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria

Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form of hypophosphatemia with hyperphosphaturia, hypercalciuria, and hypercalcemia. In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter. Our objective was to define the clinical course of these cases in a family with HHRH and to screen for SLC34A3 gene in order to determine whether these mutations are responsible for HHRH.Methods: After clinical and biochemical evaluations, the entire SLC34A3 gene was screened using PCR amplification followed by direct sequencing technique. In this paper, we describe a new kindred with HHRH and a case of progressive and complicated HHRH presenting at age 27 years.Results: We found 101-bp deletion in intron 9 of the SLC34A3 gene. The index patient was homozygous for this mutation which has been previously reported in a Caucasian population. This is the first report for presence of SLC34A3 intron 9 deletion in an Iranian population.Conclusions: These data showed that HHRH can be easily missed or underdiagnosed. Genetic evaluation of patients with familial hypercalciuria, hypophosphatemia and nephrolithiasis is needed for further information on the prevalence and management of this rare disorder. Conflict of interest:None declared.     

Synthesis,characterization, molecular docking,and biological activities of coumarin–1,2,3-triazole-acetamide hybrid derivatives

Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin–1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin–1,2,3-triazole-acetamide hybrids showed K_i values in the range of 483.50–1,243.04 nM against hCA I, 508.55–1,284.36 nM against hCA II, 24.85–132.85 nM against AChE, 27.17–1,104.36 nM against BChE, 590.42–1,104.36 nM against α-Gly, and 55.38–128.63 nM against α-Amy. The novel coumarin–1,2,3-triazole-acetamide hybrids had effective inhibition profiles against all tested metabolic enzymes. Also, due to the enzyme inhibitory effects of the new hybrids, they are potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus (T2DM), Alzheimer's disease (AD), and leukemia. Additionally, these inhibition effects were compared with standard enzyme inhibitors like acetazolamide (for hCA I and II), tacrine (for AChE and BChE), and acarbose (for α-Gly and α-Amy). Also, those coumarin–1,2,3-triazole-acetamide hybrids with the best inhibition score were docked into the active site of the indicated metabolic enzymes.