KBG syndrome

KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and developmental delay. To date, KBG syndrome has been reported in 45 patients. Clinical features observed in more than half of patients that may support the diagnosis are short stature, electroencephalogram (EEG) anomalies (with or without seizures) and abnormal hair implantation. Cutaneous syndactyly, webbed short neck, cryptorchidism, hearing loss, palatal defects, strabismus and congenital heart defects are less common findings. Autosomal dominant transmission has been observed in some families, and it is predominantly the mother, often showing a milder clinical picture, that transmits the disease. The diagnosis is currently based solely on clinical findings as the aetiology is unknown. The final diagnosis is generally achieved after the eruption of upper permanent central incisors at 7–8 years of age when the management of possible congenital anomalies should have been already planned. A full developmental assessment should be done at diagnosis and, if delays are noted, an infant stimulation program should be initiated. Subsequent management and follow-up should include an EEG, complete orthodontic evaluation, skeletal investigation with particular regard to spine curvatures and limb asymmetry, hearing testing and ophthalmologic assessment

Mesiodistal root angulation of permanent teeth in children with mixed dentition and normal occlusion

OBJECTIVE: There is little information regarding the mesiodistal angulation of permanent teeth in mixed dentition. The aim of this study was to evaluate mesiodistal root angulation of permanent incisors, canines and first molars of 100 Brazilian children, using a new horizontal reference plane based on the midpoint of the intercuspation of primary canines and permanent first molars in panoramic radiographs during the mixed-dentition phase. MATERIAL AND METHODS: Children were equally divided between the genders with a mean age of 8.9 years (SD=0.76), normal occlusion and no eruptive disturbances. RESULTS: The angulation of the permanent maxillary first molars was close to the vertical, whereas the mandibular molars presented approximately 25 degrees of distal root angulation. The maxillary canines were the most distally angulated teeth, whereas the permanent mandibular canines were vertically positioned. The evaluation of the anterior maxillary area showed vertical position of permanent lateral, and central incisors with a slight distal angulation, whereas the permanent mandibular incisors tended to a mesial radicular convergence. CONCLUSIONS: The proposed reference line could be useful in mixed dentition root angulation evaluation; there was a slight asymmetry in the mesiodistal angulation among homologous teeth, and also a small variation between the male and the female groups, but no difference between 8-and 10-year-old children

Is the process of delivery of an individually tailored lifestyle intervention associated with improvements in LDL cholesterol and multiple lifestyle behaviours in people with Familial Hypercholesterolemia?

<p>Abstract</p> <p>Background</p> <p>More insight in the association between reach, dose and fidelity of intervention components and effects is needed. In the current study, we aimed to evaluate reach, dose and fidelity of an individually tailored lifestyle intervention in people with Familial Hypercholesterolemia (FH) and the association between intervention dose and changes in LDL-Cholesterol (LDL-C), and multiple lifestyle behaviours at 12-months follow-up.</p> <p>Methods</p> <p>Participants (n = 181) randomly allocated to the intervention group received the PRO-FIT intervention consisting of computer-tailored lifestyle advice (<it>PRO-FIT*advice</it>) and counselling (face-to-face and telephone booster calls) using Motivational Interviewing (MI). According to a process evaluation plan, intervention reach, dose delivered and received, and MI fidelity were assessed using the recruitment database, website/counselling logs and the Motivational Interviewing Treatment Integrity (MITI 3.1.1.) code. Regression analyses were conducted to explore differences between participant and non-participant characteristics, and the association between intervention dose and change in LDL-C, and multiple lifestyle behaviours.</p> <p>Results</p> <p>A 34% (n = 181) representative proportion of the intended intervention group was reached during the recruitment phase; participants did not differ from non-participants (n = 623) on age, gender and LDL-C levels. Of the participants, 95% received a <it>PRO-FIT*advice</it> log on account, of which 49% actually logged on and completed at least one advice module. Nearly all participants received a face-to-face counselling session and on average, 4.2 telephone booster calls were delivered. None of the face-to-face sessions were implemented according to MI guidelines. Overall, weak non-significant positive associations were found between intervention dose and LDL-C and lifestyle behaviours.</p> <p>Conclusions</p> <p>Implementation of the PRO-FIT intervention in practice appears feasible, particularly <it>PRO-FIT*advice</it>, since it can be relative easily implemented with a high dose delivered. However, only less than half of the intervention group received the complete intervention-package as intended. Strategies to let participants optimally engage in using web-based computer-tailored interventions like <it>PRO-FIT*advice</it> are needed. Further, more emphasis should be put on more extensive MI training and monitoring/supervision.</p> <p>Trial registration</p> <p>NTR1899 at ww.trialregister.nl.</p

Both the C-Terminal Polylysine Region and the Farnesylation of K-RasB Are Important for Its Specific Interaction with Calmodulin

Background: Ras protein, as one of intracellular signal switches, plays various roles in several cell activities such as differentiation and proliferation. There is considerable evidence showing that calmodulin (CaM) binds to K-RasB and dissociates K-RasB from membrane and that the inactivation of CaM is able to induce K-RasB activation. However, the mechanism for the interaction of CaM with K-RasB is not well understood. Methodology/Principal Findings: Here, by applying fluorescence spectroscopy and isothermal titration calorimetry, we have obtained thermodynamic parameters for the interaction between these two proteins and identified the important elements of K-RasB for its interaction with Ca 2+ /CaM. One K-RasB molecule interacts with one CaM molecule in a GTP dependent manner with moderate, micromolar affinity at physiological pH and physiologic ionic strength. Mutation in the polybasic domain of K-Ras decreases the binding affinity. By using a chimera in which the C-terminal polylysine region of K-RasB has been replaced with that of H-Ras and vice versa, we find that at physiological pH, H-Ras-(KKKKKK) and Ca 2+ /CaM formed a 1:1 complex with an equilibrium association constant around 10 5 M 21, whereas no binding reaction of K-RasB-(DESGPC) with Ca 2+ /CaM is detected. Furthermore, the interaction of K-RasB with Ca 2+ /CaM is found to be enhanced by the farnesylation of K-RasB. Conclusions/Significance: We demonstrate that the polylysine region of K-RasB not only contributes importantly to th