Vortexes tune the chirality of graphene oxide and its non-covalent hosts.

Graphene oxide (GO) is one of the most appealing bidimensional materials able to interact non-covalently with achiral molecules and to act as chiral inducers. Vortexes can tune chirality and, consequently transfer a specific handedness to non-covalent host molecules, either when dispersed in water or when deposited on a solid surface.

Benefits and shortcomings of superselective transarterial embolization of renal tumors before zero ischemia laparoscopic partial nephrectomy.

AIMS: To report feasibility, safety and effectiveness of "zero-ischemia" laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. METHODS: We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. RESULTS: Mean patients age was 68 years (range 56-74), mean tumor size was 3.5 cm (range 2.2-6.3 cm). STE was successfully completed in 16 patients 12-15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a "zero-ischemia" approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5-22). Mean operative time was 123 min (range 115-130) and mean intraoperative blood loss was 250 mL (range 20-450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. CONCLUSIONS: STE is a viable option to perform "zero-ischemia" LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases.

Laser assisted green synthesis of free standing reduced graphene oxides at the water-air interface.

A single step, scalable and green strategy has been developed to obtain reduced graphene oxide layers in water dispersion through nanosecond laser pulse irradiation of carbon targets. The layers spontaneously migrate at the water-air interface, forming sheets of several tens of micrometers and show intense ultraviolet photoluminescence. This unique condition offers an intriguing environment where opposing dielectric media meet and can be used in all those processes where molecular interactions such as hydrogen bonding and electrostatic interactions are greatly enhanced.

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer.

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.

Seminal sparing cystectomy and ileocapsuloplasty: long-term followup results.

PURPOSE: The efficacy of nerve sparing techniques to save potency in cystoprostatectomy is about 50%. This radical surgery may be proposed to young men with normal sexual function. We report the results of a 13-year experience with our innovative seminal sparing cystectomy and bladder replacement to maintain sexual function in such patients. MATERIALS AND METHODS: Seminal sparing cystectomy is a modification of standard radical cystectomy in which the posterior bladder dissection is anterior to the seminal vesicle plane to preserve the vasa deferens, seminal vesicles, prostatic capsule and neurovascular bundles. Ablation of the whole bladder and the prostatic urothelium with surrounding hypertrophic tissue is guaranteed, and injury to the pelvic nerve plexus that provides autonomic innervation to the corpora cavernosa is avoided. From April 1990 to December 2002 we performed 68 procedures in 63 patients (7 of whom were lost to followup) with superficial bladder cancer resistant to conservative therapies (18 patients with stage T1G2 disease, 13 TaG2, 11 T1G3 and 14 TaG3) and in 5 patients with invasive bladder cancer (T2G3) which was monofocal and away from the bladder neck. All patients had normal sexual function. A complete clinical evaluation (with prostate specific antigen [PSA], digital rectal examination and transrectal ultrasound) to exclude concomitant prostate cancer was performed. Average patient age was 49 years and mean followup was 68 months. RESULTS: Normal erectile function was preserved in 58 patients (95%). Complete daytime continence was reached in 58 patients (95%) and nighttime continence was reached in 19 patients (31%). The early postoperative complication rate was 18% and the delayed complication rate was 26.2%. A total of 55 patients (90.2%) are alive and 6 patients (9.8%) died, 5 of cancer progression. High grade prostatic intraepithelial neoplasia was noticed in prostatic specimens in 3 patients and prostatic cancer was noted in 1 patient. These patients had a normal PSA before operation and a serum PSA less than 0.2 ng/ml at a mean followup of 19 months. No positive margins were identified on permanent histological analysis of the specimens, nor were local pelvic recurrences observed. CONCLUSIONS: Our innovative technique is safe, effective and easy to perform. The oncological and functional results obtained with a long followup justify seminal sparing cystectomy as an excellent surgical procedure which can be proposed to some oncological and nononcological cases.

Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity.

BACKGROUND: Melanocortin-4 receptor (MC4R) mutations have been reported as the most common single genetic cause of obesity in some populations and it has been suggested that they may be responsible for more than 4% of early-onset obesity. OBJECTIVES: To verify the presence of mutations of the MC4R coding region in children from southern Italy with early-onset obesity. SUBJECTS AND METHODS: Two-hundred and eight unrelated obese children and adolescents were included in the study. The average age at obesity onset was 4.5+/-2.6 y. MC4R coding region was screened using both single-strand conformation polymorphism (SSCP) analysis and denaturing high-performance liquid chromatography (DHPLC). Automatic sequencing of PCR products of all individuals that showed an aberrant SSCP and/or DHPLC pattern was performed. RESULTS: One novel missense mutation and one previously described polymorphism (Vall03Ile) were identified. The missense mutation C142T, resulting in the substitution of proline with serine at codon 48, within the first MC4R transmembrane domain, was detected at the heterozygous state in a 15-y-old obese girl (body mass index (BMI)=35 kg/m(2)) who has been obese since she was 8 y old. The mutation co-segregated with the obesity phenotype for over three generations and was not found in the control population. CONCLUSIONS: Our data show MC4R obesity causing mutations in less than 0.5% of the patients (ie 1 out of 208 patients) and therefore indicate a low prevalence of MC4R variants in the obese population from southern Italy. The specific genetic background of the Mediterranean population could make it difficult for MC4R mutations to produce an essentially polygenic trait such as common obesity, at least during childhood.

Conservative treatment of iatrogenic urinary fistulas: the value of cyanoacrylic glue.

Once previously attempted conservative maneuvers have failed, iatrogenic persistent urinary fistulas usually require difficult repeated operations. We describe 3 patients in whom cyanoacrylic glue was used to repair endoscopically persistent urinary fistulas occurring after major pelvic surgery. At a mean follow-up of 21 months, all patients were free of urinary leakage and had no evidence of recurrent urinary fistulas. This approach may represent a safe and effective way to repair postoperative urinary fistulas.

Mutational screening of the CART gene in obese children: identifying a mutation (Leu34Phe) associated with reduced resting energy expenditure and cosegregating with obesity phenotype in a large family.

Cocaine- and amphetamine-regulated transcript (CART) inhibits feeding and induces the expression of c-Fos in hypothalamic areas implicated in appetite regulation. Furthermore, the CART peptide is found in neurons regulating sympathetic outflow, which in turn play an integral role in regulating body temperature and energy expenditure. The CART gene was screened by single-strand conformation polymorphism and automatic sequencing in 130 (72 girls) unrelated obese Italian children and adolescents. Their Z-scores (mean +/- SD) of relative to BMI percentiles was 3.9 +/- 1.8, and the average age at obesity onset was 4.7 +/- 2.6 years. Two previously described silent polymorphisms were found in the 3' untranslated region: an adenine deletion at position 1457 in 9 patients (allele frequency 0.035) and an A/G substitution at position 1475 in 11 patients (allele frequency 0.042). We found no difference between the obese patients heterozygous for one of these polymorphisms and those patients homozygous for the wild allele with respect to their age of obesity onset, BMI Z-scores, and leptin levels. A missense mutation of G729C resulting in the substitution of Leu with Phe at codon 34, within the NH2-terminal CART region, has been detected in the heterozygous state in a 10-year-old obese boy who has been obese since the age of 2 years. The patient belongs to a large family of obese subjects. The mutation cosegregated with the severe obesity phenotype over three generations and was not found in the control population. Resting metabolic rates were lower than expected in the propositus (-14%) and his mother (-16%), who carried the mutation. Leucine at codon 34, conserved in this position in the human and in the rat sequences, immediately precedes a couple of lysine residues that may well represent a dibasic processing site. The Leu34Phe mutation might alter the susceptibility to proteolysis of this potential processing site, likely altering the CART effect on thermogenesis and energy expenditure.

Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese children: report of three new mutations.

BACKGROUND: Although linkage studies strongly suggest that proopiomelanocortin (POMC) alterations could play a role in the genetic predisposition to obesity, systematic POMC mutational analysis did not completely confirm this hypothesis. OBJECTIVES: To verify the presence of mutations of the POMC coding region in Italian children with very early onset obesity. SUBJECTS AND METHODS: Eighty seven unrelated Italian obese children and adolescents were studied. Mean age at obesity onset was 4.7+/-2.5 y. The POMC gene coding region was screened using single-strand conformation polymorphism (SSCP) analysis. Bi-directional automatic sequencing of PCR products was performed for all individuals who showed an aberrant SSCP pattern. RESULTS: Three new mutations have been identified in the heterozygous state in three patients: (a) G3834C, resulting in the substitution of Ser with Thr at codon 7 within the POMC signal peptide; (b) C3840T, resulting in the substitution of Ser with Leu at codon 9 of the pre-proopiomelanocortin signal peptide; and (c) C7406G, producing the substitution of Arg with Gly at codon 236 within the beta-endorphin peptide. A polymorphism consisting of a 9 bp insertion, AGC AGC CGC, between position 6997 and 6998 has been found at the heterozygous state in nine patients. They showed leptin levels adjusted for BMI, gender and pubertal stage significantly higher than obese subjects homozyous for the POMC wild-type allele. CONCLUSIONS: Mutations in codons 7 and 9 of the signal peptide may alter the translocation of the pre-proopiomelanocortin into the endoplasmic reticulum and, therefore, can be implicated in obesity. Although further studies are required, the polymorphism between position 6997 and 6998 may represent one of the genetic variations that explain the linkage between obesity and POMC. International Journal of Obesity (2001) 25, 61-67

Clinical and molecular evaluation of non-dominant hereditary spherocytosis.

About 75% of hereditary spherocytosis (HS) patients have the autosomal dominant form of the disease, whereas both parents of the remaining HS patients are clinically and haematologically normal. These patients could have either the autosomal recessive form of the disease or a de novo mutation. We studied 80 randomly chosen, Italian HS children with normal parents. They had different clinical phenotypes (16 mild, 40 moderate, 16 moderately severe and eight severe). These patients were screened for the occurrence of ankyrin or beta-spectrin de novo mutations. To search for ankyrin de novo mutations affecting mRNA accumulation, we studied a (AC)(n) microsatellite located in the non-coding sequence of the last exon of the ankyrin gene, and four different exonic polymorphisms in the beta-spectrin gene were utilized for the detection of de novo mutations influencing beta-spectrin mRNA stability. They were also screened for the presence of alpha-spectrin(LEPRA) as well as for the mutation -108T-->C in the ankyrin promoter, two variants previously found in some cases of genuinely recessive HS. Twenty-five patients showed ankyrin de novo mutations and 10 HS subjects had beta-spectrin de novo mutations. Furthermore, we found five patients to be heterozygous for alpha-spectrin(LEPRA) and one heterozygous for the mutation in the ankyrin promoter. Therefore, a molecular diagnosis was achieved in about 50% of the cases. Our data demonstrate that, among HS patients with normal parents, de novo dominant mutants are six times more common than recessive mutations. These results should be considered in view of the genetic counselling of a normal couple with a HS child.

Induction and potentiation of parturition in fingernail clams (Sphaerium striatinum) by selective serotonin re-uptake inhibitors (SSRIs).

Parturition in fingernail clams (Sphaerium spp.) can be induced by external application of serotonin and serotonergic ligands. Selective serotonin re-uptake inhibitors (SSRIs) increase neurotransmission at serotonergic synapses by blocking re-uptake transporters. We tested the efficacy of SSRIs (fluvoxamine, fluoxetine, paroxetine) at inducing parturition in the fingernail clam Sphaerium striatinum. Parturition was induced by fluvoxamine and paroxetine, but only potentiated by fluoxetine. Fluvoxamine was potent, significantly inducing parturition at concentrations from 10 nM to 100 microM compared with negative controls. Fluvoxamine also significantly potentiated a subthreshold (10 microM) concentration of serotonin. Paroxetine also induced parturition but was less potent. Only 10 microM paroxetine significantly induced parturition compared with controls. Fluoxetine (1-100 microM) did not induce any parturitions, but at 5 microM it potentiated parturition in subthreshold serotonin concentrations as low as 50 nM. These results suggest the presence of serotonin re-uptake transporters in bivalve molluscs and may provide a way of stimulating serotonergic mechanisms without using serotonin or its ligands.

Polytetrafluoroethylene giant granuloma and adenopathy: long-term complications following subureteral polytetrafluoroethylene injection for the treatment of vesicoureteral reflux in children.

PURPOSE: The use of polytetrafluoroethylene as bulking agent for the endoscopic treatment of vesicoureteral reflux in children has raised many concerns about the implant histocompatibility and the risk of migration of polytetrafluoroethylene particles. We report on 3 cases of long-term complications following subureteral polytetrafluoroethylene injection (STING) and an extensive review of the literature is presented. MATERIALS AND METHODS: Between January 1993 and December 1995, 3 children (2 males, 1 female; 4, 7 and 6 years old), previously submitted to STING, underwent open surgery for recurrent vesicoureteral reflux. RESULTS: In 1 case a hard nodular mass, strictly adherent to the ureteral wall, was a foreign body giant granuloma. All patients demonstrated a heavy multinucleated foreign body reaction around polytetrafluoroethylene particles in the pelvic nodes. CONCLUSIONS: Many experimental studies and some clinical observations have demonstrated that polytetrafluoroethylene particles elicit a foreign body granulomatous reaction and have the tendency to migrate. Until the long-term effects of their presence are well known, STING should be carefully evaluated in children and young patients.

Renal agenesis, ureteral ectopia into seminal vesicle, vas deferens agenesis and hemivertebra: an incomplete form of caudal regression syndrome?

The association of seminal vesicle cyst and upper urinary tract malformation is well known in the literature [1]. More rarely, urogenital malformations are associated with vertebral [2] or anorectal anomalies [3]. A 35-year-old infertile man with unilateral renal and deferential agenesis, seminal vesicle cyst and hemivertebra is reported. This complex malformative syndrome has been reported previously by Sheih et al. [4] and, to our knowledge, this is the third case described in the literature.