Deep brain stimulation of the forniceal area enhances memory functions in experimental dementia: The role of stimulation parameters

Deep brain stimulation (DBS) is currently being evaluated as a potential therapy in improving memory functions in Alzheimer’s disease. The target for DBS and the stimulation parameters to be used are unknown. Here, we implanted bilateral electrodes in the vicinity of the fornix, a key element of the memory circuitry, and applied DBS with different stimulation frequencies and amplitudes in an experimental model of dementia. Rats received scopolamine, a muscarinic acetylcholine receptor antagonist, to mimic memory impairment. Rats were then tested in the object location task with the following conditions: (i) with attachment of stimulation cable (off stimulation), and (ii) with DBS at various amplitudes (50 μA, 100 μA and 200 μA), 100 μs pulse width and 100 Hz or 10 Hz stimulation frequency. DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that the fornix is not sensitive to the frequency of stimulation, but rather to current levels. With the most optimal stimulation parameter, we found no side-effects on anxiety levels and general motor activity. These findings identify the fornix as a key region in controlling spatial memory functions. DBS of this region, using tailored stimulation parameters, has the potential to improve memory functions in conditions characterised by memory impairment.     

Effect of bioactive borate glass microstructure on bone regeneration,angiogenesis, and hydroxyapatite conversion in a rat calvarial defect model

Borate bioactive glasses are biocompatible and enhance new bone formation, but the effect of their microstructure on bone regeneration has received little attention. In this study scaffolds of borate bioactive glass (1393B3) with three different microstructures (trabecular, fibrous, and oriented) were compared for their capacity to regenerate bone in a rat calvarial defect model. 12 weeks post-implantation the amount of new bone, mineralization, and blood vessel area in the scaffolds were evaluated using histomorphometric analysis and scanning electron microscopy. The amount of new bone formed was 33%, 23%, and 15%, respectively, of the total defect area for the trabecular, oriented, and fibrous microstructures. In comparison, the percent new bone formed in implants composed of silicate 45S5 bioactive glass particles (250–300 μm) was 19%. Doping the borate glass with copper (0.4 wt.% CuO) had little effect on bone regeneration in the trabecular and oriented scaffolds, but significantly enhanced bone regeneration in the fibrous scaffolds (from 15 to 33%). The scaffolds were completely converted to hydroxyapatite within the 12 week implantation. The amount of hydroxyapatite formed, 22%, 35%, and 48%, respectively, for the trabecular, oriented, and fibrous scaffolds, increased with increasing volume fraction of glass in the as-fabricated scaffold. Blood vessels infiltrated into all the scaffolds, but the trabecular scaffolds had a higher average blood vessel area compared with the oriented and fibrous scaffolds. While all three scaffold microstructures were effective in supporting bone regeneration, the trabecular scaffolds supported more bone formation and may be more promising in bone repair.     

The processing of ultrafine-grained Mg tubes for biodegradable stents

An investigation was carried out on equal-channel angular pressing (ECAP) and extrusion processing of a ZM21 Mg alloy to obtain an improved candidate material for the manufacturing of biodegradable Mg stents. Ultrafine-grain size billets of the ZM21 alloy were obtained by two-stage ECAP aimed at achieving an initial refining of the structure at 200 °C and then reaching the submicrometer grain size range by lowering the processing temperature down to 150 °C. The investigation revealed a significant improvement in the properties of the ECAP-treated samples compared with the starting coarse-grained ZM21 alloy. The 0.2% yield strength rose from 180 to 340 MPa after 150 °C ECAP processing, while maintaining a fairly high tensile ductility. The ultrafine ZM21 alloy billets were then used for the extrusion of stent precursors having the form of small-size tubes. The grain size after extrusion remained in the submicrometer range while the hardness was revealed to be significantly higher than that of the coarse-grained ZM21 Mg alloy. It was demonstrated that processing of biodegradable Mg stent having an ultrafine-grained microstructure by ECAP and low-temperature extrusion is feasible and that the obtained products feature promising properties.     

Cenani–Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation

Cenani–Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T > C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype–phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.     

Early assessment of percutaneous coronary interventions for chronic total occlusions analyzed by novel echocardiographic techniques

OBJECTIVE:

Successful revascularization of chronic total occlusions has been associated with improved left ventricular systolic function, reduced anginal symptoms, increased exercise capacity, and increased survival. This study was conducted to determine the impact of revascularization in chronic total occlusion on left ventricular function using novel echocardiographic techniques.

METHODS:

A total of 129 patients with chronic total occlusion who underwent revascularization between April 2011 and November 2012 were included in this study. Echocardiographic assessments with two-dimensional speckle tracking echocardiography and real-time three-dimensional echocardiography were performed before the procedure and one month after the procedure. The left ventricular ejection fraction, left ventricular volumes, and three-dimensional systolic dyssynchrony index were quantified.

RESULTS:

An immediate procedural success was obtained in 118 patients (91.5%). There were no acute or subacute stent thromboses during follow-up. The mean left ventricular ejection fraction significantly increased (p<0.001), while the left ventricular end-diastolic and end-systolic volumes significantly decreased (p = 0.001 and p<0.001, respectively). The three-dimensional systolic dyssynchrony index also decreased significantly (p<0.001). The global longitudinal strain showed a significant increase after successful revascularization (p<0.001). An increase in the global longitudinal strain was correlated with an increase in the left ventricular ejection fraction (r = 0.27, p = 0.02). The patients with a left ventricular ejection fraction ≥50% displayed a greater improvement in the global longitudinal strain, and the patients with diabetes showed less improvement.

CONCLUSIONS:

Using novel echocardiographic techniques, our results showed that restoring the coronary blood flow in chronic total occlusion patients reduces the left ventricular volumes and improves the left ventricular ejection fraction and the global longitudinal strain of hibernating myocardium.     

Hematological alterations induced by phenol exposure in Oncorhynchus mykiss

In the present study, the impacts of phenol, a pollutant of inland water habitats, were investigated on Oncorhynchus mykiss. The fish (weight?=?300?±?7.5 g, total length?=?18.58?±?3.8 cm) were subjected to 0.6, 1.2, and 2.4 mg/l of phenol concentration for 8 weeks. At the end of study, blood samples were taken via cardiac puncture by heparinized syringes, and hematological assays were done by standard methods. Red blood cell counts, hematocrit, hemoglobin concentration, and mean corpuscular hemoglobin concentration value decreased after phenol exposure while white blood cells counts showed an increase. The values of mean corpuscular hemoglobin and mean corpuscular volume were not affected by phenol treatment. Our findings showed that hematological parameters can be used as diagnostic indices to evaluate the health status of O. mykiss after exposure to phenol.     

Narasin poisoning in the dromedary camel (Camelus dromedarius)

Narasin poisoning was reported in 15 camels, 7 adults and 8 young, after accidental access to poultry feed medicated with 60 g narasin per ton. Fourteen camels died between 3 and 20 days, and one young animal survived the dose after developing a chronic course of a disease. The main clinical signs of narasin toxicity in the dromedary include: weakness of hind limbs, lack of coordination, oedema of dependent parts, inappetence, ruminal atony, myoglobinuria, profound depression, tachycardia, sternal recumbency and death. The lesions were mainly in the heart and skeletal muscles and consisted of multifocal degeneration and necrosis of heart and skeletal muscle fibres with areas of regeneration and lung oedema. There was high enzyme activity for creatine kinase (CK), lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase and an increase in urea concentration and white blood cells, neutrophil and platelet counts. Cardiac markers, troponin T, CK-MB and C-reactive protein, showed slight or no changes terminally.     

Evaluation of the effect of static magnetic field in treatment of tendon injuries in dog

To assess the effect of magnetic field in experimental tendon injuries, ten clinically healthy adult indigenous dogs were divided into two equal groups (control and experimental). The left superficial digital flexor tendon was exposed and three windows of 6 mm thickness, 3 mm length, and 2 mm intervals were made under general anesthesia. In the experimental group, the dogs were subjected to a magnetic field of 6?×?800 G for 30 days. The tendon biopsy was collected from the site of operation on the postoperative day 30. Histomorphological changes indicated low rate of inflammatory cells, high rate of mature fibroblast, and increased normal collagen fibers, and these were better in the experimental group. The biomechanical test revealed that the tendons of the dogs in the experimental group were more resistant than tendons of the dogs in the control group. The result of this study indicated that magnetic field therapy reduced edema and local swelling, enhanced proliferation of fibroblasts, and regulated arrangement of collagen fibers, providing a good noninvasive physical therapy for tendinous injuries.