NRG1 gene in recurrent major depression: no association in a large-scale case-control association study.

The Neuregulin 1 (NRG1) gene was initially implicated in schizophrenia (SZ) and has recently been associated with bipolar disorder (BPD) in two studies. An association with major depressive disorder (MDD) has not yet been investigated but is warranted in view of the genetic overlap between MDD and BPD. We have performed a large-scale case-control study investigating the association between NRG1 polymorphisms and MDD, genotyping a selection of 14 single nucleotide polymorphisms (SNPs) spanning the NRG1 gene in a sample of 1,398 patients of White European ancestry with a diagnosis of MDD and 1,304 ethnically matched controls from three clinical sites in the UK. We found no single marker or haplotype associations that withstood correction for multiple testing. Our findings do not provide evidence that NRG1 plays a role in MDD or that this gene explains part of the genetic overlap with BPD.

Association of DISC1 and TSNAX genes and affective disorders in the depression case-control (DeCC) and bipolar affective case-control (BACCS) studies.

The gene known as Disrupted-in-Schizophrenia-1, DISC1, was originally discovered in a large family, in which it also co-segregated with bipolar affective disorder (BD) and with major depressive disorder (MDD). The TSNAX (Translin-associated factor X) gene, located immediately upstream of DISC1, has also been suggested as a candidate gene in relation to psychiatric illness, as one transcript resulting from intergenic splicing encodes a novel TSNAX-DISC1 fusion protein. We explored the TSNAX-DISC1 gene region for an association with BD and MDD in a sample of 1984 patients (1469 MDD, 515 BD) and 1376 ethnically matched controls. Eight single nucleotide polymorphisms (SNPs) within the TSNAX-DISC1 region (rs766288, rs3738401, rs2492367, rs6675281, rs12133766, rs1000731, rs7546310 and rs821597) were investigated using the SNPlex Genotyping System. We found a significant allelic and genotypic association of the TSNAX-DISC1 gene region with BD, whereas a haplotypic association was found for both BD and MDD. Therefore, our results suggest an association between the TSNAX-DISC1 region and both forms of affective disorders, and support the hypothesis that a portion of the genotypic overlap between schizophrenia and affective disorders is attributable to this gene.

New two-dimensional global longitudinal strain and strain rate imaging for assessment of systemic right ventricular function.

OBJECTIVES: To determine the usefulness of new two-dimensional strain indices, based on speckle tracking imaging, for assessment of systemic right ventricular (RV) function after an atrial switch operation for transposition of the great arteries. DESIGN: Cross-sectional study. SETTING: Tertiary paediatric cardiac centre. METHODS: 26 patients, mean (SD) age 21.0 (3.6) years at 19.9 (3.2) years after an atrial switch operation, and 27 age-matched controls were studied. Two-dimensional imaging at the four-chamber view was obtained with tracing of the entire RV endocardial border. The RV global longitudinal strain (GLS) and GLS rate were derived using automated software (EchoPAC, GE Medical) and correlated with tissue Doppler-derived RV isovolumic acceleration (IVA), and, in the patient cohort, with cardiac magnetic resonance-derived RV ejection fraction. RESULTS: Intra- and interobserver variability for measurement of GLS, as determined from the mean (SD) of differences in two consecutive results from 20 studies, were 0.06 (1.39)% and 0.24 (1.77)%, respectively. Compared with controls, patients had lower RV GLS (17.1 (1.9)% vs 26.3 (2.9)%, p<0.001), a reduced GLS rate (0.78 (0.11)/s vs 1.33 (0.23)/s, p<0.001), lower RV IVA (1.10 (0.36) m/s(2) vs 1.56 (0.53) m/s(2), p<0.001) and increased RV myocardial performance index (0.52 (0.09) vs 0.38 (0.09), p<0.001). Both RV GLS and GLS rate correlated positively with RV IVA (r = 0.43, p = 0.001 and r = 0.46, p<0.001, respectively), and negatively with RV myocardial performance index (r = -0.65, p<0.001 and r = -0.57, p<0.001, respectively). In patients, the GLS rate correlated positively with RV ejection fraction (r = 0.62, p = 0.001). CONCLUSIONS: Two-dimensional RV GLS and GLS rate are new, potentially useful indices for assessment of systemic RV function.

Management and outcome of antenatally diagnosed congenital cystic adenomatoid malformation of the lung.

OBJECTIVE: To review the management and outcome of babies with antenatally diagnosed congenital cystic adenomatoid malformation. DESIGN: Retrospective cohort review. SETTING: Tertiary neonatal care unit at Queen Mary Hospital and antenatal diagnostic centre at Tsan Yuk Hospital. PATIENTS: Consecutive patients with antenatally suspected congenital cystic adenomatoid malformation in their concepti among antenatal patients attending Tsan Yuk Hospital from 1994 to 2002. Twenty-four of 33 cases were referred to Queen Mary Hospital for postnatal management and for whom comprehensive records were available for analysis in 23. INTERVENTIONS: Postnatal interventions in their babies included investigational imaging for congenital cystic adenomatoid malformation and surgery. MAIN OUTCOME MEASURES: Antenatal and postnatal outcome, as well as pathology of the excised lesions. RESULTS: Antenatal outcome: termination of pregnancy in two cases and spontaneous abortion in one; in-utero regression was documented in nine cases and in one hydropic change was apparent. Postnatal outcome: only eight of 20 babies born alive had symptoms in neonatal period. Two developed serious infective complications in infancy, one with documented in-utero regression. Pulmonary parenchymal abnormalities were detected on computed tomography of the thorax in six of seven cases with normal or non-specific chest radiograph findings. Among nine cases with in-utero regression, congenital cystic adenomatoid malformation was confirmed by operative histology in five and abnormal computed tomography findings in three. Fifteen babies underwent surgical excision, one of whom died because of severe pre-existing pulmonary hypoplasia and nine endured minor postoperative complications. A favourable outcome was documented at a mean follow-up of 22 months (range, 2 months-7 years). CONCLUSIONS: In-utero regression of congenital cystic adenomatoid malformation on antenatal ultrasound may not represent genuine resolution. Computed tomographic thorax should be considered in all newborns with antenatally diagnosed congenital cystic adenomatoid malformation, and if confirmed early operation before first hospital discharge is recommended.

Low-energy charge-density excitations in MgB2: Striking interplay between single-particle and collective behavior for large momenta.

A sharp feature in the charge-density excitation spectra of single-crystal MgB2, displaying a remarkable cosinelike, periodic energy dispersion with momentum transfer (q) along the c* axis, has been observed for the first time by high-resolution nonresonant inelastic x-ray scattering (NIXS). Time-dependent density-functional theory calculations show that the physics underlying the NIXS data is strong coupling between single-particle and collective degrees of freedom, mediated by large crystal local-field effects. As a result, the small-q collective mode residing in the single-particle excitation gap of the B pi bands reappears periodically in higher Brillouin zones. The NIXS data thus embody a novel signature of the layered electronic structure of MgB2.

Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaemia major.

An increased iron store has been linked to the risk of atherosclerosis. The carotid intima-media thickness (IMT), stiffness index, Young's elastic modulus (YEM), and augmentation index were determined in 20 patients with beta-thalassaemia major. Compared with controls, patients had greater IMT (P < 0.001), YEM (P = 0.005), and stiffness (P = 0.009) and augmentation (P = 0.03) indices. The odds ratio for increased IMT in patients was 39. Carotid IMT correlated with YEM (P = 0.036), stiffness index (P = 0.036) and augmentation index (P = 0.006). Multivariate analysis identified patient status (P < 0.001) as the only significant determinant of IMT. These findings suggest the possibility of premature atherosclerosis in beta-thalassaemia major patients.

Ordering of hydrogen bonds in high-pressure low-temperature H2O.

The near K-edge structure of oxygen in liquid water and ices III, II, and IX at 0.25 GPa and several low temperatures down to 4 K has been studied using inelastic x-ray scattering at 9884.7 eV with a total energy resolution of 305 and 175 meV. A marked decrease of the preedge intensity from the liquid phase and ice III to ices II and IX is attributed to ordering of the hydrogen bonds in the proton-ordered lattice of the latter phases. Density functional theory calculations including the influence of the Madelung potential of the ice IX crystal correctly account for the remaining preedge feature. Furthermore, we obtain spectroscopic evidence suggesting a possible new phase of ice at temperatures between 4 and 50 K.

Use of oral valaciclovir in a 12-year-old boy with herpes simplex encephalitis.

We report on a 12-year-old boy with herpes simplex encephalitis, in whom a severe localised skin reaction developed following the infusion of intravenous acyclovir. Oral valaciclovir was given as continuation therapy to complete the 3-week course of antiviral treatment and resulted in complete recovery without side effects. This report illustrates the advantage of using the polymerase chain reaction to diagnose herpes simplex encephalitis and the potential use of newer antiviral agents, such as valaciclovir, as continuation therapy in the management of the infection. The higher oral bioavailability of newer antiviral agents allows part of the extended treatment period of patients with herpes simplex encephalitis to be carried out as an ambulatory oral regimen.

The quantitative determination of cilostazol and its four metabolites in human liver microsomal incubation mixtures by high-performance liquid chromatography.

A high-performance liquid chromatography-ultraviolet (HPLC-UV) method for the quantitation of cilostazol and four of its principal metabolites (i.e. OPC-13015, OPC-13213, OPC-13217 and OPC-13326) in human liver microsomal solutions was developed and validated. Cilostazol, its metabolites, and the internal standard (OPC-3930), were analyzed by protein precipitation followed by reverse-phase HPLC separation on a TSK-Gel ODS-80TM (150 x 4.6 mm, 5 microm) column and a Cosmil C-18 column (150 x 4.6 mm, 5 microm) in tandem and UV detection at 254 nm. An 80 min gradient elution of mobile phase acetonitrile in acetate buffer (pH = 6.50) was used to obtain quality chromatography and peak resolution. All the analytes were separated from each other, with the resolution being 2.43-17.59. The components of liver microsomal incubation mixture and five metabolic inhibitor probes (quinidine sulfate, diethyl dithiocarbamate (DEDTC), omeprazole, ketoconazole and furafylline) did not interfere with this analytical method. The LOQ was 1000 ng ml(-1) for cilostazol and 100 ng ml(-1) for each of the metabolites. This method has been validated for linear ranges of 100-4000 ng ml(-1) for OPC-13213, OPC-13217 and OPC-13326; 100-2000 ng ml(-1) for OPC-13015; and 1000-20000 ng ml(-1) for cilostazol. The percent relative recovery of this method was established to be 81.2-101.0% for analytes, with the precision (% coefficient of variation (CV)) being 2.8-7.7%. The autosampler stability of the analytes was evaluated and it was found that all analytes were stable at room temperature for a period of at least 17 h. This assay has been shown to be precise, accurate and reproducible.

Excimer laser photorefractive keratectomy for myopia: six-month follow-up.

In this study, 108 eyes of 62 patients had photorefractive keratectomy (PRK) with a 193 nm excimer laser to correct myopia. The eyes were assigned to one of three groups: low, moderate, or high myopia. Six months after PRK, 88.9% of eyes in the low myopia group, 90.0% in the moderate myopia group, and 23.8% in the high myopia group achieved an uncorrected visual acuity of 20/40 or better. In the low myopia group, 88.9% were within +/- 1 diopter (D) of attempted correction, as were 70.0% in the moderate group and 18.8% in the high myopia group. There were no significant complications. We conclude that excimer laser PRK appears to be a safe and relatively accurate procedure to correct low to moderate myopia but not high myopia because of regression over time.

Recursive parameter identification of constrained systems: an application to electrically stimulated muscle.

In the application of real-time identification methods for diagnosis or adaptive control of biomedical systems, there is often known model information that is ignored. Constraints on the allowable values of parameters, which may be based on physical considerations, are often neglected because the information does "fit" easily into commonly used parameter-identification algorithms. In this paper a method of incorporating constraints on model parameters is developed. This method is applicable to most recursive parameter-identification algorithms. It enforces linear equality constraints on identified parameters. The use of this method for the real-time identification of autoregressive moving-average-type time series models, subject to parameter constraints, is described in detail. These constraints may be time varying. At each time step, the parameter estimate obtained by a recursive least squares estimator is orthogonally projected onto the constraint surface. This simple idea, when appropriately executed, enhances the output prediction accuracy of estimated parameters. Using constraint information in this way is important when we do not wish to destroy a "natural" parameterization of the model (by an initial projection to incorporate equality constraints), or when we cannot use a single initial model simplification (because the constraints are time varying or involve inputs and outputs). Because it improves output prediction at future times, this method is advantageous for use in predictive adaptive controllers. The use of this algorithm is demonstrated in the identification of electrically stimulated quadriceps muscles in paraplegic human subjects, using percutaneous intramuscular electrodes. The nonlinear steady-state force versus pulsewidth recruitment characteristic of the electrode-muscle system is identified simultaneously with the input-output muscle response dynamics, using a Hammerstein-type model. Knowledge of the recruitment curve's shape is translated into constraints on the identified parameters. This information improves the experimental predictive quality of the identified model.

Stability of one-stage adjustable suture for the correction of horizontal strabismus.

One-stage adjustable suture for strabismus correction, with the whole operation done under topical anaesthesia and adjustment done on the table, was performed on 45 consecutive patients. The stability of the post-adjustment result was studied by comparing the post-adjustment deviation on the operating table to that at six weeks and three months after operation. The stability was comparable to that following the usual two-stage adjustable suture. The original angle of deviation and the fusion status were found to have no bearing on the stability of the procedure.

Transcriptional regulation of two genes specifically induced by glucose starvation in a hamster mutant fibroblast cell line.

This report concerns the characterization of the RNA transcripts encoded by two cDNA sequences p4A3 and p3C5, derived from a hamster temperature-sensitive mutant cell line K12. Using the two cDNA sequences as hybridization probes, we show that they occur as single copy genes in the hamster genome and encode for RNA transcripts which are highly inducible in K12 cells at 40.5 degrees C. After incubation at 40.5 degrees C for 16 h, there is a 10-fold increase in the p4A3 and p3C5 mRNA levels, reaching a final concentration of about 1% of the cytoplasmic polyadenylated RNA. We demonstrate that the kinetics of transcription of p4A3 and p3C5 directly parallel the accumulation of the mRNA levels at 40.5 degrees C. Thus, our data indicate that the expression of these two genes are primarily regulated at the transcriptional level. In addition, there is a 3- to 4-fold increase in the p4A3 and p3C5 mRNA levels when the cells are specifically starved of glucose. This implies that the expression of these two genes are stringently regulated by the availability of glucose in the culture medium. The relationship between the cDNA clones and two glucose-regulated proteins which are overproduced in K12 cells at 40.5 degrees C is discussed.