Structural genomic variation in childhood epilepsies with complex phenotypes

A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies.     

Enhancement in the performance of nanostructured CuO–ZnO solar cells by band alignment

In this study, we investigated the effect of cobalt doping on band alignment and the performance of nanostructured ZnO/CuO heterojunction solar cells. ZnO nanorods and CuO nanostructures were fabricated by a low-temperature and cost-effective chemical bath deposition technique. The band offsets between Zn_1−xCo_xO (x = 0, 0.05, 0.10, 0.15, and 0.20) and CuO nanostructures were estimated using X-ray photoelectron spectroscopy and it was observed that the reduction of the conduction band offset with CuO. This also results in an enhancement in the open-circuit voltage. It was demonstrated that an optimal amount of cobalt doping could effectively passivate the ZnO related defects, resulting in a suitable conduction band offset, suppressing interface recombination, and enhancing conductivity and mobility. The capacitance–voltage analysis demonstrated the effectiveness of cobalt doping on enhancing the depletion width and built-in potential. Through impedance spectroscopy analysis, it was shown that recombination resistance increased up to 10% cobalt doping, thus decreased charge recombination at the interface. Further, it was demonstrated that the insertion of a thin layer of molybdenum oxide (MoO₃) between the active layer (CuO) and the gold electrode hinders the formation of a Schottky junction and improved charge extraction at the interface. The ZnO/CuO solar cells with 10% cobalt doped ZnO and 20 nm thick MoO₃ buffer layer achieved the best power conversion efficiency of 2.11%. Our results demonstrate the crucial role of the band alignment on the performance of the ZnO/CuO heterojunction solar cells and could pave the way for further progress on improving conversion efficiency in oxide-based heterojunction solar cells.

Nanostructured ZnO/CuO photovoltaic cell with power conversion efficiency of 2.11%.     

Laparoscopic aneurysm resection and splenectomy for splenic artery aneurysm in the third trimester of pregnancy

Background

Splenic artery aneurysms (SAA) are a rare entity most commonly diagnosed incidentally. Their association with pregnancy increases the risk of rupture resulting in a disproportionately high maternal and fetal mortality. Accordingly, elective surgical treatment is recommended in asymptomatic patients with aneurysms less than 2 cm. In this case, we present a patient during her third trimester of pregnancy with a SAA who was treated by laparoscopic aneurysm resection and splenectomy.

Methods

The patient is a 38-year-old multiparous woman, with an incidental diagnosis of a SAA in 2010. Subsequently, the patient became pregnant and at 27 weeks started to develop abdominal pain. Failed embolization was attempted with worsening of the patient’s symptoms. A CT angiogram revealed a 1.6 cm distal third SAA without any evidence of rupture. Due to the localization of the lesion, the patient was offered a laparoscopic aneurysm resection and splenectomy.

Results

Operating time was 90 min and estimated blood loss was 5 cc. Postoperative fetal monitoring was normal. No perioperative complications were observed. The patient was discharged on postoperative day 3. Two months after laparoscopic splenectomy, the patient delivered a male infant in perfect health.

Conclusions

Although this is a rare disease, the risk of aneurysmal rupture is increased during pregnancy. As a result of high maternal and fetal mortality, elective surgery should be performed. Laparoscopic surgery is the technique of choice.     

Localized, aggregative, and diffuse adherence to HeLa cells, plastic, and human small intestines by Escherichia coli isolated from patients with diarrhea.

Adherence of diarrhea-associated Escherichia coli was studied by scanning electron microscopy. Enteropathogenic E. coli (EPEC) adherence factor-positive (EAF+) E. coli of EPEC serotypes (class I EPEC) adhered to plastic and human jejunal and ileal mucosa, similar to case and HeLa cells. Localized adherence, elongation of cell microvilli, and "locking" of the bacterial aggregates by the elongated microvilli were evident after incubation for 20 min. EAF+ E. coli adhered strikingly to mucus but rarely to M cells in Peyer's patch-associated epithelium. Most enteroaggregative E. coli (EAggEC) strains adhered to plastic, similar to HeLa cells. Some diffuse-adhering E. coli (DAEC) strains displayed no adherence to plastic but formed "dimples" on HeLa cells. Both EAggEC and DAEC adhered at lower levels to human small intestines (except M cells) than did EAF+ E. coli. In all cases of EAF+ E. coli, EAggEC, and DAEC, strains were found with atypical characteristics. The data demonstrate the unique adherence characteristics of EAF+ E. coli, EAggEC, and DAEC.     

Phosphorylation of cytosolic proteins by resting and activated human neutrophils

A study was conducted on the phosphorylation of proteins in the neutrophil cytosol in response to phorbol myristate acetate (PMA) and N- formyl-methionyl-leucyl-phenylalanine (fMLP). Autoradiography of gel electrophoretograms prepared from neutrophils incubated with 32Pi in the presence and absence of the activators showed nine proteins whose state of phosphorylation was affected by neutrophil activation. 32P was gained by eight of these proteins and was lost by the ninth. For all but one of these proteins, the change in the extent of labeling appeared to reach completion by one to two minutes. It was possible to quantitate the changes in 32P content of three of the nine proteins. One of these was the 20-kD protein that lost label when the neutrophils were activated. Quantitation showed that over half the 32P present in this protein in the resting state was gone within 0.2 minutes after activation. The other two were proteins weighing 11 and 69 kD. The phosphorylation characteristics of these two proteins differed, depending on whether activation had been carried out with PMA or fMLP. These differences in protein phosphorylation support other evidence suggesting that PMA and fMLP do not activate neutrophils by identical biochemical pathways. Differences in phosphorylation between resting and activated cells were not affected by dibutyryl cyclic guanosine monophosphate (cGMP), dibutyryl cyclic adenosine monophosphate (cAMP), theophylline, aspirin, hydrocortisone, or colchicine. The differences were abolished, however, by 30 mumol/L trifluoperazine. This finding is consistent with the hypothesis that the calcium/calmodulin system plays a biochemical role in the activation of neutrophils.     

Lipotoxicity,neuroinflammation, glial cells and oestrogenic compounds

The high concentrations of free fatty acids as a consequence of obesity and being overweight have become risk factors for the development of different diseases, including neurodegenerative ailments. Free fatty acids are strongly related to inflammatory events, causing cellular and tissue alterations in the brain, including cell death, deficits in neurogenesis and gliogenesis, and cognitive decline. It has been reported that people with a high body mass index have a higher risk of suffering from Alzheimer's disease. Hormones such as oestradiol not only have beneficial effects on brain tissue, but also exert some adverse effects on peripheral tissues, including the ovary and breast. For this reason, some studies have evaluated the protective effect of oestrogen receptor (ER) agonists with more specific tissue activities, such as the neuroactive steroid tibolone. Activation of ERs positively affects the expression of pro‐survival factors and cell signalling pathways, thus promoting cell survival. This review aims to discuss the relationship between lipotoxicity and the development of neurodegenerative diseases. We also elaborate on the cellular and molecular mechanisms involved in neuroprotection induced by oestrogens.     

Isolated congenital tuberculosis otitis in a preterm infant

We report an unusual case of localized congenital tuberculosis otitis in a preterm infant. Unlike disseminated congenital cases, the manifestations of localized otitis are associated with a triad of signs: (i) regional lymphadenopathy in the absence of typical systemic features of tuberculosis; (ii) delayed onset of presentation; and (iii) refractory otitis unresponsive to conventional antimicrobial agents. The need for greater diligence in looking for neonatal tuberculosis is emphasized, especially in an ethnic or socioeconomic environment where the disease is prevalent. Congenital tuberculosis, otitis, preterm
PC Ng, Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong     

Chronic radiographic lung changes in children with vertically transmitted HIV-1 infection

OBJECTIVE: We prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 to determine the incidence of chronic radiographic lung changes (CRC) and to correlate these changes with clinical assessments. SUBJECTS AND METHODS: Between 1990 and 1997, we scored 3050 chest radiographs using a standardized form. Group I children (n = 201) were HIV-1-infected at enrollment. Group II children (n = 512) were enrolled prenatally or before 28 days postpartum and subsequently subdivided into group IIa (n = 86), children identified as HIV-1-infected; and group IIb (n = 426), those who were HIV-1-uninfected. CRC were defined as parenchymal consolidations or nodular disease lasting 3 months or more or increased bronchovascular markings or reticular densities lasting 6 months or more. Morbidity was assessed by CD4 counts, viral load, the presence of low oxygen saturation, wheezing, tachypnea, crackles, and clubbing. RESULTS: The cumulative incidence of chronic radiographic lung changes in HIV-1-infected children was 32.8% by 4 years old, with increased bronchovascular markings or reticular densities being most common. Chronic changes were associated with lower CD4 cell counts and higher viral loads. Resolution of these chronic changes was associated with decreasing CD4 cell counts but not with lower rates of clinical findings, viral load, or difference in survival. CONCLUSION: With increased survival, CRC are becoming more common. The resolution of these changes may indicate immunologic deterioration rather than clinical improvement.