BackgroundFive regulatory factor X (RFX) transcription factors (TFs)–RFX1-5–have been previously characterized in the human genome, which have been demonstrated to be critical for development and are associated with an expanding list of serious human disease conditions including major histocompatibility (MHC) class II deficiency and ciliaophathies.ResultsIn this study, we have identified two additional RFX genes–RFX6 and RFX7–in the current human genome sequences. Both RFX6 and RFX7 are demonstrated to be winged-helix TFs and have well conserved RFX DNA binding domains (DBDs), which are also found in winged-helix TFs RFX1-5. Phylogenetic analysis suggests that the RFX family in the human genome has undergone at least three gene duplications in evolution and the seven human RFX genes can be clearly categorized into three subgroups: (1) RFX1-3, (2) RFX4 and RFX6, and (3) RFX5 and RFX7. Our functional genomics analysis suggests that RFX6 and RFX7 have distinct expression profiles. RFX6 is expressed almost exclusively in the pancreatic islets, while RFX7 has high ubiquitous expression in nearly all tissues examined, particularly in various brain tissues.ConclusionThe identification and further characterization of these two novel RFX genes hold promise for gaining critical insight into development and many disease conditions in mammals, potentially leading to identification of disease genes and biomarkers.

a b s t r a c tAims: We aim to review the results, complications and outcomes of a single surgeon's series of lower limb lengthening in patients with achondroplasia.Methods: Ten achondroplastic children underwent limb lengthening. The patients, medical records and radiographs were reviewed. Results:The average age at the time of the index operation was 7.8 years. A single surgeon undertook all procedures. The average total length gain was 20.5 cm. The commonest complication was a fractured femur after removal of the frame.Conclusion: Although complication rates were high (70%), none were left with any long-term sequelae and all were pleased with the results.

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Background/ObjectivesA large intake of walnuts may improve lipid profile and endothelial function. The effect of moderate walnut consumption is not known. We investigated whether a moderate intake of walnuts would affect lipid profile, arterial stiffness and platelet activation in healthy volunteers.Subjects/MethodsThirty healthy males were recruited into a single-blind randomised controlled crossover trial of 4 weeks dietary walnut supplementation (15 g/day) and 4 weeks control (no walnuts). Arterial stiffness was assessed using pulse waveform analysis to determine the augmentation index and augmented pressure. Platelet activation was determined using flow cytometry to measure circulating platelet-monocyte aggregates.ResultsThere were no differences in lipid profile after 4 weeks of walnut supplementation compared with control. Dietary intake of alpha-linolenic acid was increased during the walnut diet (2.1±0.4 g/day versus 0.7±0.4 g/day, P<0.0001). There were no differences in augmentation index or augmented pressure during walnut supplementation. Walnut supplementation did not affect platelet-monocyte aggregation .ConclusionsDietary intervention with a moderate intake of walnuts does not affect lipid profile, arterial stiffness or platelet activation in man. Our results suggest that the potentially beneficial cardiac effects of walnuts may not be apparent at lower and more practical levels of consumption.

Objective: Diazoxide is first-line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide-induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide-induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide-treated patients with HH. Design and Patients:Retrospective cohort study involving four UK regional HH centres; review of case notes of HH patients on diazoxide. Measurements:The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment-related risk factors were analysed for association.Results: Thirteen (6 men) of 177 HH diazoxide-treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months.Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019). Conclusion:Pulmonary hypertension can occur in 7% of diazoxide-treated HH patients. Risk factors include the presence of congenital heart disease and fluid overload.Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops. K E Y W O R D Sdiazoxide, echocardiography, hyperinsulinism, hypoglycaemia, pulmonary hypertension | 771 CHEN Et al.