Screening of nucleotide variations in genomic sequences encoding charged protein regions in the human genome.

BACKGROUND: Studying genetic variation distribution in proteins containing charged regions, called charge clusters (CCs), is of great interest to unravel their functional role. Charge clusters are 20 to 75 residue segments with high net positive charge, high net negative charge, or high total charge relative to the overall charge composition of the protein. We previously developed a bioinformatics tool (FCCP) to detect charge clusters in proteomes and scanned the human proteome for the occurrence of CCs. In this paper we investigate the genetic variations in the human proteins harbouring CCs. RESULTS: We studied the coding regions of 317 positively charged clusters and 1020 negatively charged ones previously detected in human proteins. Results revealed that coding parts of CCs are richer in sequence variants than their corresponding genes, full mRNAs, and exonic + intronic sequences and that these variants are predominately rare (Minor allele frequency < 0.005). Furthermore, variants occurring in the coding parts of positively charged regions of proteins are more often pathogenic than those occurring in negatively charged ones. Classification of variants according to their types showed that substitution is the major type followed by Indels (Insertions-deletions). Concerning substitutions, it was found that within clusters of both charges, the charged amino acids were the greatest loser groups whereas polar residues were the greatest gainers. CONCLUSIONS: Our findings highlight the prominent features of the human charged regions from the DNA up to the protein sequence which might provide potential clues to improve the current understanding of those charged regions and their implication in the emergence of diseases.

[Post traumatic rupture in patients with uretero pelvic junction obstruction. Case report]. / Rupture post - traumatique d'un syndrome de la jonction pyelo -ureterale meconnu. A propos d'une observation.

Authors report a case of post traumatic pelvic rupture occurring in an unknown ureteropelvic junction (UPJ) obstruction. Ultrasonography showed pyelectasia and fluid effusion in the anterior perirenal space. CT scan confirmed the diagnosis of UPJ obstruction and showed the rupture of the anterior pelvic wall communicating with a perirenal urinoma. The patient underwent a retrograde stenting for decompression and surgical drainage of the urinoma. Pyeloplasty was performed 4 months after injury. A follow up intravenous pyelogram showed good flow through the repair and the patient remaines asymptomatic 2 years after treatment. Post traumatic rupture of UPJ obstruction is a rare event with few reported cases in literature. Diagnosis is suggested on imaging studies. CT scan shows the rupture site in the ureteropelvic tract and guides percutaneous drainage.

Prevalence of alternative diagnoses in patients with suspected uncomplicated renal colic undergoing computed tomography: a prospective study.

OBJECTIVES: Unenhanced computed tomography (CT) has become a standard imaging technique for uncomplicated renal colic in many countries. The appropriate timing of CT imaging has not been established, and guidelines recommend that this imaging be performed between 1 and 7 days of presentation. The primary objective of this study was to determine the prevalence of alternative diagnosis identified with low-dose unenhanced CT in the emergency department (ED) in patients with suspected uncomplicated renal colic. METHODS: This prospective single-centre study was carried out in a large university hospital ED. Over a 6-month period, all patients with clinically diagnosed renal colic and a plan to be discharged underwent low-dose unenhanced CT in the ED. Pregnant women, women of childbearing age not willing to have a pregnancy test, and patients who had already undergone diagnostic imaging were excluded. The primary outcome was the number and nature of the alternative diagnosis. Univariate analyses were performed to assess factors associated with the primary outcome. RESULTS: A total of 178 patients were screened, and 155 underwent CT in the ED. The mean age was 42.2 years; 69% were male. The diagnosis of uncomplicated renal colic was confirmed in 118 participants (76%); 27 (17%) had an inconclusive CT scan. Overall, 10 patients (6%; 95% confidence interval [CI] 3-10) had an alternative diagnosis, 5 of whom were subsequently hospitalized. CONCLUSION: Low-dose unenhanced CT in the ED detects alternative diagnoses in 6% (95% CI 3-10) of patients with suspected uncomplicated renal colic, half of whom are subsequently hospitalized. Our prospective findings, which were similar to those reported in retrospective studies, are a potential argument for a systematic approach to ED imaging in suspected renal colic. Future research involving intervention and control groups would be helpful.

Accuracy of high resolution (1.5 tesla) pelvic phased array magnetic resonance imaging (MRI) in staging prostate cancer in candidates for radical prostatectomy: results from a prospective study.

OBJECTIVE: To evaluate the role of pelvic phased array MRI in staging prostate cancer (CaP). MATERIALS AND METHODS: We prospectively collected data over 12 months on CaP patients who underwent preoperative MR imaging with a pelvic phased array before radical prostatectomy. MR images were analyzed prospectively by 2 radiologists. MR imaging findings were then correlated with pathologic findings. RESULTS: Overall, 101 patients were included with a mean PSA level of 8 (range 1.8-30). Reader 1 (AUC 0.895, 95% CI 0.791-0.999) had a higher performance than reader 2 (AUC 0.687, 95% CI, 0.555-0.819) and than DRE (AUC 0.728, 95% CI, 0.599-0.857) in discriminating T2 from T3 CaP (P = 0.01). The κ-index of inter-observer agreement was 0.56. A model that combines MRI findings, DRE, PSA, and Gleason score was the most competitive for staging (AUC 0.895, 95% CI, 0.791-0.999). For the multivariate analysis, 3 criteria were significantly associated with extracapsular extension: asymmetry of the neuro-vascular bundles (P = 0.001), asymmetric enhancement of neurovascular bundles (P = 0.02), and bulging of the capsule (P = 0.0003). CONCLUSION: Pelvic phased array MRI presented satisfying results in its ability to adequately stage CaP and notably in detecting the extracapsular extension of tumors. It is likely to provide reliable information but rather in the hands of an experienced radiologist.

Effects of bed-time insulin versus pioglitazone on abdominal fat accumulation, inflammation and gene expression in adipose tissue in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Intra-abdominal fat (IAF) and inflammatory markers are correlated with cardio-vascular risk. We compared the impact of bed-time insulin versus pioglitazone treatment on these parameters in type 2 diabetic (T2D) patients. METHODS: Twenty-eight T2D patients poorly controlled with metformin and sulfonylurea were randomized to receive add-on therapy with pioglitazone or bed-time NPH insulin. IAF and subcutaneous fat (SCF) content, systemic low-grade inflammation level and expression of inflammation related genes in SCF, were measured before and after 24 weeks of treatment. RESULTS: Insulin and pioglitazone resulted in a significant decrease in HbA1c (-1.6% and -1.2%, respectively) and a significant increase in total body fat mass (1+/-2.3 and 3.3+/-2.7 kg, respectively). There was no change in IAF content after both treatments whereas significant increase in SCF content was only seen after pioglitazone treatment (p<0.05 versus insulin). hsCRP level decreased after pioglitazone and ferritin level decreased after insulin treatment. No change in mRNA expression of inflammation related genes was found after either treatment. CONCLUSION/INTERPRETATION: This suggests that a 24-week treatment with pioglitazone or bed-time insulin has a similar impact on intra-abdominal fat mass and systemic low-grade inflammation.