A higher rare CNV burden in the genetic background potentially contributes to intellectual disability phenotypes in 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS), the most common survivable human genetic deletion disorder, is caused by a hemizygous deletion of 30–40 contiguous genes on chromosome 22, many of which have not been well characterized. Clinical features seen in patients with this deletion, including intellectual disability, are not completely penetrant and vary in severity between patients, suggesting the involvement of variants elsewhere in the genome in the manifestation of the phenotype. Given that it is a relatively rare disorder (1/2000-6000 in humans), limited research has shed light into the contribution of these second-site variants to the developmental pathogenesis that underlies 22q11DS. As CNVs throughout the genome might constitute such a genetic risk factor for variability in the 22q11DS phenotypes such as intellectual disability, we sought to determine if the overall burden of rare CNVs in the genetic background influenced the phenotypic variability. We analyzed CNV and clinical data from 66 individuals with 22q11DS, and found that 77% (51/66) of individuals with the 22q11DS also carry additional rare CNVs (<0.1% frequency). We observed several trends between CNV burden and phenotype, including that the burden of large rare CNVs (>200 Kb in size) was significantly higher in 22q11DS individuals with intellectual disability than with normal IQ. Our analysis shows that rare CNVs may contribute to intellectual disability 22q11DS, and further analysis on larger 22q11DS cohorts should be performed to confirm this correlation.     

Managing acute colorectal obstruction by "bridge stenting" to laparoscopic surgery: Our experience

AIM: To verify the clinical results of the endoscopic stenting procedure for colorectal obstructions followed by laparoscopic colorectal resection with “one stage anastomosis”.METHODS: From March 2003 to March 2009 in our surgical department, 48 patients underwent endoscopic stenting for colorectal occlusive lesion: 30 males (62.5%) and 18 females (37.5%) with an age range from 40 years to 92 years (median age 69.5). All patients enrolled in our study were diagnosed with an intestinal obstruction originating from the colorectal tract without bowel perforation signs. Obstruction was primitive colorectal cancer in 45 cases (93.7%) and benign anastomotic stricture in 3 cases (6.3%).RESULTS: Surgical resection was totally laparoscopic in 69% of cases (24 patients) while 17% (6 patients) of cases were video-assisted due to the local extension of cancer with infiltrations of surrounding structures (urinary bladder in 2 cases, ileus and iliac vessels in the others). In 14% of cases (5 patients), resection was performed by open surgery due to the high American Society of Anesthesiologists score and the elderly age of patients (median age of 89 years). We performed a terminal stomy in only 7 patients out of 35, 6 colostomies and one ileostomy (in a total colectomy). In the other 28 cases (80%), we performed bowel anastomosis at the same time as resection, employing a temporary ileostomy only in 5 cases.CONCLUSION: Colorectal stenting transforms an emergency operation in to an elective operation performable in a totally laparoscopic manner, limiting the confection of colostomy with its correlated complications.     

Investigation on cobalt‐oxide nanoparticles cyto‐genotoxicity and inflammatory response in two types of respiratory cells

The increasing use of cobalt oxide (Co₃O₄) nanoparticles (NPs) in several applications and the suggested genotoxic potential of Co‐oxide highlight the importance of evaluating Co₃O₄ NPs toxicity. Cyto‐genotoxic and inflammatory effects induced by Co₃O₄ NPs were investigated in human alveolar (A549), and bronchial (BEAS‐2B) cells exposed to 1–40 µg ml^–1. The physicochemical properties of tested NPs were analysed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cytotoxicity was studied to analyze cell viability (WST1 test) and membrane damage (LDH assay), direct/oxidative DNA damage was assessed by the Formamido‐pyrimidine glycosylase (Fpg)‐modified comet assay and inflammation by interleukin (IL)‐6, IL‐8 and tumor necrosis factor‐alpha (TNF‐α) release (ELISA). In A549 cells, no cytotoxicity was found, whereas BEAS‐2B cells showed a viability reduction at 40 µg ml^–1 and early membrane damage at 1, 5 and 40 µg ml–1. In A549 cells, direct and oxidative DNA damage at 20 and 40 µg ml^–1 were detected without any effects on cytokine release. In BEAS‐2B cells, significant direct DNA damage at 40 µg ml^–1 and significant oxidative DNA damage with a peak at 5 µg ml^–1, that was associated with increased TNF‐α release at 1 µg ml^–1 after 2 h and increased IL‐8 release at 20 µg ml^–1 after 24 h, were detected. The findings show in the transformed alveolar cells no cytotoxicity and genotoxic/oxidative effects at 20 and 40 µg ml^–1. In normal bronchial cells, moderate cytotoxicity, direct DNA damage only at the highest concentration and significant oxidative‐inflammatory effects at lower concentrations were detected. The findings confirm the genotoxic‐oxidative potential of Co₃O₄ NPs and show greater sensitivity of BEAS‐2B cells to cytotoxic and oxidative‐inflammatory effects suggesting the use of different cell lines and multiple end‐points to elucidate Co₃O₄ NPs toxicity. Copyright © 2015 John Wiley & Sons, Ltd.     

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Annals of Nuclear Medicine - [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis...     

Psychological status in female carriers of premutation FMR1 allele showing a complex relationship with the size of CGG expansion

We utilized a sample of 299 adult females aged between 19 and 86 years, carrying fragile X mental retardation (FMR1) alleles with small CCG expansions ranging from 50 to 141 repeats to analyse the relationships between psychological symptoms as assessed by the Symptom Checklist‐90‐Revised (SCL‐90‐R) and the size of the CGG repeat in the FMR1 gene. There were highly significant (negative) correlations between the size of the CGG repeat and a great majority of SCL‐90‐R subscale scores and all the global indices, suggesting that carriers of premutations in the mid‐size CGG repeat range may be at greatest risk for the development of psychiatric disorder.