Cn29, a novel orphan peptide found in the venom of the scorpion Centruroides noxius: Structure and function.

A peptide (Cn29) from the venom of the scorpion Centruroides noxius (about 2% of the soluble venom) was purified and its primary and three-dimensional structures were determined. The peptide contains 27 amino acids with primary sequence: LCLSCRGGDYDCRVKGTCENGKCVCGS. The peptide is tightly packed by three disulfide linkages formed between C2-C23, C5-C18 and C12-C25. Since the native peptide was obtained in limited amounts, the full synthetic peptide was prepared using the standard F-moc-based solid phase synthesis method of Merrifield. The native and synthetic peptides were shown to be identical by sequencing, HPLC separation and mass spectrometry. The solution structure of the peptide solved from NMR data shows that it consists of a well-defined N-terminal region without regular secondary structure extending from Leu 1 to Asp 9, followed by a short helical fragment from Tyr10 to Val14 and two short ß strands (Thr17-Glu19 and Lys22-Val24). The primary and tertiary structures of Cn29 are different from all other scorpion peptides described in the literature. Transcriptome analysis of RNA obtained from C. noxius confirmed the expression of a gene coding for Cn29 in its venom gland. Initial experiments were conducted to identify its possible function: lethality tests in mice and insects as well as ion-channel binding using in vitro electrophysiological assays. None of the physiological or biological tests displayed any activity for this peptide, which at present is considered to be another orphan peptide found in scorpion venoms. The peptide is thus the first example of a novel structural component present in scorpion venoms.

Deafness on the island of Providencia - Colombia: different etiology, different genetic counseling.

Providencia is a small island located in the Caribbean Ocean, northwest of Colombia with an unusually high frequency of individuals with hearing loss (5 in 1,000) is present. The hearing loss in the island was characterized as non-syndromic autosomal recessive deafness accounting for 47% (8/17) of the deaf population, Waardenburg Syndrome (deafness associated with pigmentary anomalies) for 29% (5/17), and the remaining 24% (4/17) are cases of sporadic non-syndromic deafness. For appropriate genetic counseling a complete pedigree of families with deaf individuals was constructed. The 35delG mutation in GJB2 gene, which encodes connexin 26 (Cx26), is responsible for the deafness observed in the 8 individuals with autosomal recessive non-syndromic hearing loss. The deaf individuals with Waardenburg Syndrome and the sporadic cases did not have this mutation. Therefore, we present here an atypical case of an isolated community with at least two different genetic etiologies for deafness: non-syndromic genetic deafness caused by the 35delG mutation in the GJB2 gene and deafness associated with Waardenburg Syndrome not related to GJB2. In a small and isolated population, it is feasible to assume that the deafness is caused by the same factor; however, Providencia is an atypical case. Therefore, it is extremely important to define the exact etiology of deafness in each case, since different etiologies require different genetic counseling.

Identifying and reducing errors with surgical simulation.

The major determinant of a patient's safety and outcome is the skill and judgment of the surgeon. While knowledge base and decision processing are evaluated during residency, technical skills-which are at the core of the profession-are not evaluated. Innovative state of the art simulation devices that train both surgical tasks and skills, without risk to patients, should allow for the detection and analysis of errors and "near misses". Studies have validated the use of a sophisticated endoscopic sinus surgery simulator (ES3) for training residents on a procedural basis. Assessments are proceeding as to whether the integration of a comprehensive ES3 training programme into the residency curriculum will have long term effects on surgical performance and patient outcomes. Using various otolaryngology residencies, subjects are exposed to mentored training on the ES3 as well as to minimally invasive trainers such as the MIST-VR. Technical errors are identified and quantified on the simulator and intraoperatively. Through a web based database, individual performance can be compared against a national standard. An upgraded version of the ES3 will be developed which will support patient specific anatomical models. This advance will allow study of the effects of simulated rehearsal of patient specific procedures (mission rehearsal) on patient outcomes and surgical errors during the actual procedure. The information gained from these studies will help usher in the next generation of surgical simulators that are anticipated to have significant impact on patient safety.

Usher syndrome: results of a screening program in Colombia.

Otological, ophthalmological and genetic studies were performed in 46 patients with Usher syndrome, identified through a screening program in Colombia. Of them, 69.6% had Usher syndrome type I, 26.1% type II, and 4.3% type III. Thirty-three patients showed profound deafness (71.7%), while 13 (28.3%) had moderate to severe hearing loss. The ophthalmologic manifestations showed marked variability. Although the majority of the patients had serious ocular impairment before age 20, 32.6% had good central visual acuity. The prevalence of Usher syndrome in Colombia, estimated at 3.2/100,000, warrants the implementation of screening programs in schools for the deaf and for the blind. Our study confirms that Usher syndrome shows no geographic or racial variation and that the disorder has a wide variability of expression and genetic heterogeneity. The large size of the families we have detected may provide important opportunities for further genetic studies, particularly in terms of the assignment of the locus and gene mapping.

[Kaposi's sarcoma in 2 patients after renal transplantation]. / Sarcoma de Kaposi en dos pacientes postrasplante renal.

The authors present two cases of Kaposi's hemorrhagic sarcoma in renal transplant patients. The malignant condition appeared 28 and 34 months, respectively, after the transplant operation. There was and acceptable improvement of Kaposi's sarcoma in both patient with radiotherapy despite the fact that the patients continued on immunosuppression with bethametasone and azathioprine. One of the patients showed involvement of the small bowel wall with Kaposi's sarcoma at autopsy. The possible causes of the appearance of this neoplasm on these patients in discussed.