DEPDC5 mutations in familial and sporadic focal epilepsy.

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.

Effect of household passive smoking exposure on the risk of ischaemic heart disease in never-smoke female patients in Hong Kong.

OBJECTIVE: To investigate the relation between household passive smoking exposure and risk of ischaemic heart disease (IHD) among never-smoke female patients by a retrospective case-control analysis. METHODS: This study recruited 314 patients with IHD who had never smoked and 319 controls who were admitted for other reasons in the same hospital during the same period. Subjects were interviewed about their exposure to household passive smoking. The dose metrics of passive smoking exposure were evaluated by using "pack years" and "hour years", which indicated the cumulative amount and duration of exposure. The ORs and 95% CIs were computed by unconditional logistic regression, adjusted for other risk factors. RESULTS: Subjects with passive smoking exposure were associated with higher risk of IHD (OR 1.51, 95% CI 1.01 to 2.27, p = 0.043) when compared to non-exposed subjects. Subjects exposed to an average of > or =1 pack of cigarette per day had an OR of 1.69 (95% CI 1.07 to 2.68, p = 0.025). The OR was 1.52 for those exposed for > or =5 years (95% CI 1.01 to 2.29, p = 0.043) and was 1.82 for those exposed > or =4 h per day (95% CI 1.05 to 3.15, p = 0.032). Similarly, the risk of IHD increased with cumulative exposure duration, with an OR of 1.53 (95% CI 1.01 to 2.32, p = 0.043) at the exposure level > or =5 pack years, and an OR of 1.61 (95% CI 1.03 to 2.52, p = 0.037) at the exposure level > or =20 hour years. There was a significant dose-response association between the exposure measures and risk of IHD (p<0.01 for trend). CONCLUSION: Our data suggested an increased risk of IHD from passive household smoking in female never-smoke subjects, and demonstrated a dose-response association.

Ipsilateral femoral fracture non-union and delayed union treated by hybrid plate nail fixation and vascularized fibula bone grafting: a case report.

UNLABELLED: Non-union is a well recognized complication of femoral neck fractures. The decision whether to attempt fracture fixation or to resort to hip replacement is particularly difficult in patients in the borderline age group in whom complex attempts at gaining union may fail and later present a difficult revision. On the other hand the patient may be young enough that arthroplasty best be avoided . Besides, presence of ipsilateral femoral shaft fracture with delayed union in addition to the femoral neck non-union will pose major problems at operation. We share our experience in treating a femoral neck fracture non-union with ipsilateral femoral shaft delayed union in the shaft and in the distal femur in a fifty years old patient. The fracture was treated with an angle blade plate and supracondylar nail supplemented with a free vascularised fibular bone grafting and autologous cancellous graft. There was radiological union at fourth month. At sixth months, the patient was free of pain and able to walk without support. Thus, we would like to suggest that vascularised fibula bone grafting with supracondylar nailing is a viable option for this pattern of fracture. KEY WORDS: Vascularized fibular bone graft, neck of femur, femoral shaft fracture, non-union.

Femoral Shaft Cortical Pathology associated with longterm Alendronate Therapy: A New Classification.

UNLABELLED: There are reported cases of cortical reaction over the tension side of the normal femoral shafts in patients on long term treatment with alendronate, leading to subsequent femoral shaft fractures. We performed a retrospective review of patients with low-energy femoral shaft fracture on alendronate, admitted to our institution during the period 2004 to May 2009. The presence of radiological changes of cortical hypertrophy with or without Looser's zone over the tension side of the femoral bone (normal limb) was determined and correlated with clinical symptoms. Thirteen patients were identified. Average duration of alendronate use was 6.5 ± 3.3 years (ranges, two to 10 years). These radiological changes were noted in four patients. Average duration of alendronate usage in these four patients was 6.5 ± 2.4 years (ranges, 5 to10 years). Prodromal thigh pain was present in a patient, who had cortical hypertrophy with the presence of a Looser's zone traversing the cortex on the femoral shaft. One patient had Looser's zone limited at the lateral hypertrophied cortex without prodromal pain. The interobserver kappa coefficient was 0.96. A femoral radiograph should be performed in all patients who are on long-term alendronate therapy who present with thigh pain. We propose a new grading system based on our observation of the radiological features in these four cases. This new grading of the radiological spectrum of femoral shaft cortical pathology has the potential to stratify the risk of low energy femoral fracture for patients treated with long-term alendronate therapy. KEY WORDS: Femur, Cortical Hypertrophy, Looser Zone, Alendronate.

The characteristics of inguinal hernia recurrence in the modern era and the long-term outcomes after re-operation.

BACKGROUND: Re-operative hernia surgery has become more technically challenging due to the use of mesh. In addition, there has been a paucity of clinical studies. A common recommendation has been to avoid the previous site and to use a different approach. METHODS: In this study of 218 patients, the anatomical characteristics of inguinal hernia recurrences were studied in relation to the previous technique of repair, including Mesh (n = 100), Laparoscopic (n = 61) and Shouldice (n = 57). RESULTS: The most common site of recurrence was direct (58.5%) in all three groups. Femoral recurrences were significantly lower in the Laparoscopic group. Indirect and multiple recurrences were significantly lower in the Shouldice group. The operative time in the Mesh group was significantly longer due to the dissection required of the previous mesh. A pro-peritoneal mesh repair was performed for the re-operation in 13.8%, while a Shouldice repair was performed in the others. The overall follow-up rate was 75.2% for a mean of 4.8 years. The re-recurrence rate was 1.8%. CONCLUSION: The distinct patterns of recurrence reflect the relative strengths and weaknesses of the different techniques of repair and present the anatomical and technical basis for future improvements. A safe and durable repair of an inguinal hernia recurrence can be achieved through an anterior trans-inguinal approach.

Cluster synchronization and spatio-temporal dynamics in networks of oscillatory and excitable Luo-Rudy cells.

We study collective phenomena in nonhomogeneous cardiac cell culture models, including one- and two-dimensional lattices of oscillatory cells and mixtures of oscillatory and excitable cells. Individual cell dynamics is described by a modified Luo-Rudy model with depolarizing current. We focus on the transition from incoherent behavior to global synchronization via cluster synchronization regimes as coupling strength is increased. These regimes are characterized qualitatively by space-time plots and quantitatively by profiles of local frequencies and distributions of cluster sizes in dependence upon coupling strength. We describe spatio-temporal patterns arising during this transition, including pacemakers, spiral waves, and complicated irregular activity.

Tissue Doppler velocity is superior to displacement and strain mapping in predicting left ventricular reverse remodelling response after cardiac resynchronisation therapy.

OBJECTIVE: To compare the values of three different forms of tissue Doppler imaging (TDI) processing in predicting left ventricular (LV) reverse remodelling-namely, tissue velocity, displacement and strain mapping. DESIGN: Standard echocardiography with TDI was performed before and 3 months after cardiac resynchronisation therapy (CRT). SETTING: University teaching hospital. PATIENTS: 55 patients with heart failure who received CRT and were followed up for at least 3 months were recruited. INTERVENTIONS: During off-line analysis, the time to peak systolic velocity in the ejection phase, time to peak positive displacement and time to peak negative strain were measured in the six basal, six mid-segmental model. Parameters of systolic asynchrony derived by velocity, displacement and strain mapping were correlated with percentage reduction in LV end systolic volume (LVESV) and absolute gain in ejection fraction (EF). RESULTS: Among the three TDI processing technologies, all parameters of tissue velocity correlated with LV reverse remodelling (r = -0.49 to r = -0.76, all p < 0.001), but the predictive value was strongest in models with 12 LV segments. For displacement mapping, only the two parameters that included 12 LV segments correlated modestly with reduction in LVESV (r = -0.36, p < 0.05) and gain in EF. However, none of the strain mapping parameters predicted a favourable echocardiographic response. The receiver operating characteristic (ROC) curve areas were higher for parameters of tissue velocity based on 12 LV segments (ROC areas 0.88 and 0.94) than the corresponding areas derived from displacement mapping (ROC areas 0.72 and 0.71). CONCLUSION: Tissue velocity parameters of systolic asynchrony are superior to those of displacement and strain mapping in predicting LV reverse remodelling response after CRT.

Symmetric heaping in grains: a phenomenological model

Heap formation of granular materials in a vertical vibrating bed is studied by a simple model using the profile of the heap as the dynamic variable. Vibration increases the local height, but is counterbalanced by the nonlinear coupling, which tends to suppress the growth of the height. The steady state heap can be solved in closed form in terms of Jacobian elliptic functions. Phenomena such as heap formation and downward and upward heaps can be reproduced. Our results agree with the experimentally observed change of downward to upward steady heaps as the vibration strength is increased. Predictions from the model compare favorably with experimental results on heap profiles and heaping angles.