Successful treatment of immediate allogeneic myeloablative hematopoietic stem cell transplantation from a HLA‐mismatched sibling donor for active systemic epstein–barr virus‐positive T‐cell lymphoproliferative disease of childhood following primary acute epstein–barr virus infection

A 22‐year‐old female was admitted for sustained high fever and diagnosed with systemic Epstein–Barr virus‐positive T‐cell lymphoproliferative disease. As her clinical course was so aggressive, she immediately underwent allogeneic myeloablative bone marrow transplantation from an HLA‐mismatched sibling donor on hospital day 46. The patient has remained in complete remission for 3 years.     

A case‐control study and meta‐analysis reveal the association between COX‐2 G‐765C polymorphism and primary end‐stage hip and knee osteoarthritis

Background

Osteoarthritis (OA) is a popular arthrosis featured as pain, limited joint activity, and deformity. Cyclooxygenase‐2 (COX‐2) has been reported to be up‐regulated in arthritic tissues and is integral to the progression of osteoarthritis (OA). Previous studies showed the COX‐2 promoter G‐765C polymorphism could influence COX‐2 expression. However, the relationship between the variant and OA risk is contrasting.

Methods

We conducted a case‐control study with 196 primary end‐stage hip and knee OA cases and 196 controls in a Chinese Han population. Subsequently, we integrated this case‐control study in a meta‐analysis to acquire greater statistical power. The results from our case‐control study using MassARRAY genotyping technology and binary logistic regression statistical methods.

Results

The variant carriers in the Chinese Han population had a lower primary end‐stage hip and knee OA susceptibility (C vs G: OR = 0.350, 95%CI: 0.154‐0.797, P = .012; GC vs GG: adjusted OR = 0.282, 95%CI: 0.118‐0.676, P = .005). Stratification studies indicated that a higher GC frequency in women decreased not only knee OA susceptibility but also unilateral knee OA risk. The meta‐analysis showed that the variant exhibited a significantly decreased OA risk through comparisons involving allelic, homozygous, heterozygous, and dominant models.

Conclusion

Our findings suggest that the COX‐2 G‐765C polymorphism exerts a protective effect against primary end‐stage knee osteoarthritis in a female Chinese Han population.

     

Memantine delayed N‐methyl‐D‐aspartate ‐induced convulsions in neonatal rats

Memantine (1‐amino‐3,5‐dimethyladamantane) is a moderate‐affinity uncompetitive antagonist of N‐methyl‐d‐aspartate (NMDA) receptors. In this study, we have explored the effect of memantine against N‐methyl‐d‐aspartate (NMDA)‐induced seizures in neonatal rats. Here, we evaluated various behavioral seizure abnormalities in neonatal rats (Sprague–Dawley; postnatal day 9) after an intraperitoneal administration of NMDA. Further, we explored whether an acute administration of memantine could protect these neonates against different phases of convulsions induced by NMDA. In a separate study, we have compared the effect of levetiracetam in the same animal model. Exogenous administration of NMDA (30 mg/kg., i.p.) in neonatal rats resulted in arrest of activity, emprosthotonos curvature (trunk is bent forward by the entire muscles), myoclonic jerks, and forelimb/hindlimb clonus. The clonus phase in neonates was followed by loss of righting reflex and continuous seizures (for more than 5 min) suggesting status epilepticus, tonic extension, and death. Pretreatment of memantine hydrochloride (10–30 mg/kg., i.p.) dose‐dependently delayed the onset of different phases of convulsions induced by NMDA. Memantine at the highest dose was found to be ataxic in rat neonates, while lower doses were free of any observed behavioral signs of toxicity. Levetiracetam (25 mg/kg., i.p.) when administered 30 min before the NMDA challenge blocked only the jerk phase and did not affect other phases of NMDA‐induced convulsions. These data indicated that memantine and other safer uncompetitive NMDA receptor antagonists may be protective in the management of neonatal seizures.     

Micropattern size‐dependent endothelial differentiation from a human induced pluripotent stem cell line

The multifaceted extracellular milieu presents biochemical and biophysical stimuli that influence stem cell differentiation. Two‐dimensional (2D) micropatterned substrates allow the presentation of these cues in spatially defined geometries that have been demonstrated to guide stem cell fate decisions. Leveraging stem cells to reconstruct microvasculature, made up of an inner lining of endothelial cells (ECs) supported by pericytes, is critical to tissue‐engineering advances; thus, methods to improve endothelial differentiation efficiency are vital to these efforts. In this study, we examine the hypothesis that the diameter of micropatterned islands influences endothelial differentiation from human induced pluripotent stem cells (hiPSCs). Comparing island diameters of 80, 140, 225 and 500 µm, we found that co‐cultures of control ECs and pericytes did not yield variable ratios of cell types; however, when hiPSCs were differentiated toward a bicellular population of ECs and pericytes on these varying micropattern feature sizes, we found that smaller islands promoted EC differentiation efficiency, yielding a derived population composed of 70% ECs, which exhibited a greater sprouting propensity. Differentiation on the largest feature size exhibited a smaller EC yield, similar to that on non‐patterned substrates. Taken together, these data demonstrate that micropatterned islands of varying diameters can be used to modulate EC differentiation efficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

Comparison between IV immune globulin (IVIG) and anti‐D globulin for treatment of immune thrombocytopenia: a randomized open‐label study

To compare the effect of IV immune globulin (IVIG) and anti‐D globulin (anti‐D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open‐label, single‐center clinical trial was carried out in Amir‐Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti‐D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti‐D caused a quicker response on the 3rd day of treatment (P < 0.001). Both drugs caused a significant rise in number of platelets on the 7th and the 14th day of treatment. Compared to IVIG, except a significant drop in hemoglobin concentration (P < 0.001), anti‐D had lower rate of side effects including fever (P < 0.05), allergy (P < 0.01), and headache (P < 0.001). Our results showed that anti‐D was associated with rapid rise of platelets compared to IVIG. In addition, anti‐D treatment had acceptable safety profile.     

Integrating EMDR into an evolutionary‐based therapy for depression: a case study

We present an intervention in a case of major depression, where eye movement desensitization and reprocessing (EMDR) therapy was integrated into an evolutionary‐based psychotherapy for depression. At the end of the treatment and at follow up assessment we observed a more accepting disposition and decreased depressive but not anxiety symptoms.     

In vitro study of SPIO‐labeled human pancreatic cancer cell line BxPC‐3

The survivin gene is highly expressed in pancreatic cancer. The purpose of this study was to design and synthesize functionalized magnetic iron oxide nanoparticles (MNPs) targeting survivin gene for the detection of pancreatic cancer. The pancreatic cancer cell line BxPC‐3 with survivin gene expression was selected in this study. The healthy lung fibroblast cell was used as a control. Chitosan‐coated MNPs (CS@MNPs) and antisense oligodeoxynucleotide of survivin gene were conjugated to MNPs to give Sur‐MNPs. Fourier transform infrared spectroscopy was performed to confirm the conjunction of chitosan. The interactions of MNPs, CS@MNPs, and Sur‐MNPs in BxPC‐3 cells were observed, recorded and analyzed. The size, morphology, cell uptake, cytotoxicity and stability of those particles were assessed by transmission electron microscope, Prussian blue staining, MTT assay and agarose gel electrophoresis. The magnetic resonance signal intensities of pancreatic cells labeled with CS@MNPs and MNPs, and Sur‐MNPs, were compared on T₂‐weighted images. The results demonstrated that the level of cellular uptake of CS@MNPs was higher than that of naked MNPs. The Sur‐MNPs had a suitable size (12 nm sized core), high stability, no cytotoxicity and good water dispersion. Sur‐MNPs did not accumulate in healthy lung fibroblast cells, while being taken up by BxPC‐3 cells. The Sur‐MNPs in BxPC‐3 cells could be visualized on T₂‐weighted images, which suggested that Sur‐MNPs could be used to detect the expression of survivin gene. Thus, Sur‐MNPs may be a potential molecular imaging probe targeting survivin gene for early detection of pancreatic cancer cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Cannabidiol reverses the mCPP‐induced increase in marble‐burying behavior

Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties. Recent results using the marble‐burying test (MBT) suggest that CBD can also induce anticompulsive‐like effects. Meta‐chloro‐phenyl‐piperazine (mCPP) is a nonspecific serotonergic agonist (acting mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD patients and block the anticompulsive‐like effect of serotonin reuptake inhibitors (SRIs) in animal models. The aim of this study was to investigate the interference of CBD on mCPP effects in repetitive burying. Administration of mCPP showed dual effects in the MBT, increasing the number of buried marbles at lower (0.1 mg/kg) while decreasing it at higher doses (1 mg/kg), an effect not related to a general increase in anxiety‐like behavior. As found previously, CBD (30 mg/kg) and the positive control fluoxetine (FLX; 10 mg/kg) decreased burying behavior without changing general exploratory activity. A similar effect was found when subeffective doses of CBD (15 mg/kg) and FLX (3 mg/kg) were administered together. These subeffective doses alone were also able to block mCPP‐induced repetitive burying. The results, in addition to reinforcing a possible anticompulsive effect of CBD, also suggest that mCPP‐induced repetitive burying could be a useful test for the screening of compounds with presumed anticompulsive properties.