Embryonic disruption of the candidate dyslexia susceptibility gene homolog Kiaa0319-like results in neuronal migration disorders.

Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5-bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.

Heat-inducible translationally controlled tumor protein of Trichinella pseudospiralis: cloning and regulation of gene expression.

To elucidate the mechanism of inducing translationally controlled tumor protein (TCTP) in stress adaptation of adenophorean nematodes, the complete coding sequence of TCTP of the infective-stage larvae of Trichinella pseudospiralis was characterized. Two cDNA clones with different 3' untranslated region were identified. Tp-TCTP contained an open reading frame of 534 bp encoding 177 residues. The gene with five introns was expressed as histidine-tagged fusion protein having a molecular mass of 17.5 kDa. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that TCTP RNA was not accumulated when the infective-stage larvae were heat-shocked for 1 h at 45 or 60 degrees C. Using enzyme-linked immunosorbent assay and antiserum against the fusion protein, the expression of TCTP was found to be up-regulated at the translational level. The data suggest that translational regulation of TCTP may play an important role in the early heat-stress adaptation of the trichinellid. Cluster analysis demonstrated that the TCTP sequence of T. pseudospiralis is closely related to that of T. spiralis, but is diverged from the secernentean species.

Dysfunctional schemas and cognitive distortions in psychopathology: a test of the specificity hypothesis.

This study aimed at testing whether there were different types of dysfunctional schemas and cognitive distortions that could help to differentiate three emotional/behavioural problems, i.e., anxiety, depression, and aggression, from each other. Five hundred and eighty-one Chinese adolescents from five mainstream high schools in Hong Kong were recruited and completed several self-report questionnaires. Bivariate correlation showed an indiscriminate pattern of association between dysfunctional schemas, cognitive distortions, and the three emotional/behavioural problems. However, when the effects of the confounding correlated emotional/behavioural problems were controlled in regression analysis, different problems did show some specific association with different types of dysfunctional schemas and/or cognitive distortions. Despite some inconsistency, these findings generally supported a specificity hypothesis. Cognitive variables were thus not only relevant in understanding psychopathology, but their different patterns of association with anxiety, depression, and aggression also supported the separability of these three emotional/behavioural problems, despite their significant correlation.

Performance of 7- to 95-year-old individuals in a Chinese version of the category fluency test.

A version of the category fluency test including the categories of animal and transportation, was administered to 316 Chinese native speakers ranging in age from 7 to 95. Results indicated that the number of items generated in the category fluency test increases with age from childhood to adulthood with a peak performance in adults aged from 19 to 30, and then declines subsequently into late life. All participants, regardless of their age, generated more animal than transportation names. Educational level, but not gender, was a significant factor affecting their performance. The participants in all age groups committed very few intrusion and perseveration errors. The results of the present study were in general consistent with those reported in the western countries. Thus, it seems to be appropriate to apply the category fluency test, which was originally developed in western countries, for clinical use in Hong Kong.

Expanding role of flexible nephroscopy in the upper urinary tract.

Flexible nephroscopy has become an important diagnostic and therapeutic modality for urologists. We have applied the flexible nephroscope in four clinical settings: as an adjunct to rigid instruments during primary percutaneous nephrolithotomy (PCNL); in a second-look procedure to remove residual renal calculi; as the primary endoscope to treat renal calculi; and to diagnose and treat other upper urinary tract pathology. The most common application of flexible nephroscopy in our experience has been during primary PCNL after the bulk of the stone burden has been removed with the rigid nephroscope. Liberal use of the flexible endoscope in these settings may increase the stone-free rate and decrease the need for additional access tracts and procedures. In addition, patients with conduit urinary diversions may be managed using flexible nephroscopy to diagnose and treat upper tract tumors.

Effect of cardiopulmonary bypass on urethral blood flow as measured by laser Doppler flowmetry.

PURPOSE: Previous reports have implicated urethral ischemia as a potential predisposing factor for the increased incidence of urethral strictures after cardiac bypass surgery. These reports were based on indirect measurements of urethral blood flow. We directly measured and compared urethral perfusion before and during cardiopulmonary bypass. MATERIALS AND METHODS: A total of 10 patients undergoing cardiac bypass surgery (mean age 70) and 4 undergoing various surgery without cardiopulmonary bypass (mean age 54) were studied prospectively. A 16F silicone urethral catheter was placed in each patient before surgery. Urethral blood flow was measured intraoperatively using the Vasamedics PR-434 implantable prism laser probe before and during cardiopulmonary bypass. RESULTS: In the patients undergoing cardiopulmonary bypass there was an overall 50+/-28% decrease in flow (range 0 to 88%, p <0.001) compared to pre-bypass levels. Stratification of the patients into warm versus cold cardioplegia revealed a mean percent decrease in flow of 58+/-20% (range 41 to 87%, p <0.05) for the warm and 44+/-33% (range 0 to 88%, p <0.05) for the cold group. Only 1 bypass case showed no significant decrease in mean flow. There was no significant decrease in urethral blood flow in the nonbypass group. CONCLUSIONS: Our study demonstrates that there is decreased blood flow to the urethral mucosa during cardiopulmonary bypass. This finding lends support to the idea of urethral ischemia as a contributing factor in the pathogenesis of urethral strictures following cardiac bypass surgery.

Ureteroscopic treatment of symptomatic caliceal diverticular calculi.

Renal calculi that reside in caliceal diverticula are difficult to treat. Numerous treatment modalities have been used, including extracorporeal shock wave lithotripsy, laparoscopy, and percutaneous treatment. All therapies directed at fragmenting the stones are limited by the ability of these fragments to pass through the narrow diverticular neck. More recently, the retrograde approach using small-caliber flexible ureteroscopes has been applied successfully in the treatment of diverticular calculi. A description of our retrograde technique is presented. The ultimate success of this technique is dependent upon familiarity with the basic principles of ureteroscopy and successful clearance of stone fragments from the diverticulum.

ECMO and the management of congenital diaphragmatic hernia with large diaphragmatic defects requiring a prosthetic patch.

From 1977 to 1991, 136 neonates have had corrective surgery for diaphragmatic hernia at Children's Hospital of Los Angeles. A retrospective study was performed to determine how many of the 136 neonates had defects large enough to require the use of a prosthetic patch to repair the defect. Twelve were found. All 12 were symptomatic at birth for respiratory distress. Mean arterial blood gas values at birth were pH 6.95, PCO2 94.8, and PO2 47.2. The mean oxygen index (n = 10) was 61.8. Six of these patients were repaired without extracorporeal membrane oxygenation (ECMO) support while the other six received ECMO bypass perioperatively. All six of the patients who did not receive ECMO support died despite successful diaphragmatic repair. Five of six patients who received ECMO perioperatively survived (83%). These surviving infants are now between 1 month and 4 years of age. In the survivors, four of five required subsequent repair and patch enlargement for a recurrent diaphragmatic hernia. Gastroesophageal reflux, requiring a Nissen fundoplication in two infants, complicated the course of three survivors. Four survivors were discharged with supplemental oxygen therapy lasting less than 13 months. Patch disruption is predicted to occur at approximately 18 months of age in all patients, especially if little or no muscle was available at primary repair for prosthetic attachment. These children should be followed closely for feeding or respiratory symptoms. Diagnosis of patch disruption can be made by chest x-rays and confirmed by contrast studies. Patch expansion by laparotomy and careful search for additional musculature for patch attachment is recommended when reherniation occurs.