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In spermatozoa, the nuclear F-actin supports the acroplaxome, a subacrosomal structure involved in the correct exposure of several acrosomal membrane proteins; among them, the glycoprotein IZUMO1 is the major protein involved in sperm-oocyte fusion. Nuclear F-actin is also involved in sperm head shaping and chromosome compartmentalization. To date, few notions regarding the bivalent role of F-actin on sperm chromatin organization and IZUMO1 positioning have been reported. In our work, we characterized subcellular organization of F-actin in human high- and low-quality spermatozoa (A- and B-SPZ), respectively, showing that F-actin over-expression in sperm head of B-SPZ affected IZUMO1 localization. A correct IZUMO1 repositioning following in vitro induction of F-actin depolymerization, by cytochalasin D treatment, occurred. Interestingly, F-actin depolymerization was also associated with a correct acrosome repositioning, thus to favor a proper acrosome reaction onset, with changes in sperm nuclear size parameters and histone acetylation rate reaching high-quality conditions. In conclusion, the current work shows a key role of F-actin in the control of IZUMO1 localization as well as chromatin remodeling and acetylation events.

The curative hepatocellular carcinoma (HCC) therapy was traditionally based on surgical or loco-regional ablation approach. However, HCC is a solid tumor characterized by a highest level of vascularization; therefore, angiogenesis inhibitor could play a pivotal role in the pharmacological therapeutic approach. Despite the low number of approved drugs, a wide range of multi-kinase and MET inhibitor is currently being evaluated in phase II and III study. In this review, we described all the drugs that have shown efficacy in recently and ongoing trials. Moreover, the immunotherapy represents a recent challenge in the HCC treatment. The strategy based on the production of multi-epitope, multi-HLA peptide vaccine naturally processed and presented on primary tumor tissues of HCC patients. A further upgrade of cancer vaccine could be represented by the combination of metronomic chemotherapy and checkpoint inhibitors.

Survival of preterm infants have dramatically improved over the last decades. Nonetheless, infants born preterm remain vulnerable to many complications, including necrotizing enterocolitis (NEC). The severity of the disease and the mortality rate are directly correlated with decreasing gestational age and birth weight. Despite surgical treatment mortality rate remains very high in extremely premature infants, especially in newborns at the lowest limit of viability. Survival of infants of birth weight (BW) below 750 g has been increasingly reported in recent years, however the overall mortality in extremely low "BW" infants (ELBW) requiring surgery for NEC has not decreased over the past years. We describe our experience with a male preterm infant who survived after an ileostomy procedure for Bell stage II NEC, with improving neuromotor skills at 2 years follow up. Although standard indication to surgery is Bell stage III, in our case the choice of minimal laparotomy, exploration of the bowel and ileostomy at Bell stage II was safe and effective. Our experience suggest that surgery has not a negative impact on survival and ileostomy could prevent further damage of the bowel in NEC. We hypothesize that indication to surgery at an earlier stage may prevent further progression of the disease without a significantly negative impact on survival. Further studies are needed to confirm the appropriateness of this approach in ELBW infants.

Aim. Aim of the study was to compare multichannel intraluminal impedance (MII)-pH monitoring versus pH only, as first-line assessment of gastroesophageal reflux (GER) in children and to define the relation between GER and symptoms as well relation between types of GER and age of children.Methods. All the patients with GER were divided in three groups: A, younger than 24 months, B, older than 24 months with typical symptoms and C, older than 24 months with atypical symptoms. The groups A and C underwent a combined MII-pH recording. The group B underwent a only pH recording. MII-pH measurements were performed in 89 children (63 group A and 26 group C), only pH measurements in 170 cases (group B).Results. Sixty-seven of the 247 pH measurements demonstrated abnormal reflux indices: 25.0% (group A), 28.8% (group B) and 20.8% (group C). The number of the reflux periods and the total reflux index were highest in the patients of the group B, but the number of long reflux periods was highest in the group C. Abnormal values at Mil results were found in 36 cases: 41.7% in group A (high number of weakly acid refluxes events) and 45.8% in group C (similar number of acid and weakly acid events). The Mil were considered pathological because of high number of reflux episodes and symptom index £50% respectively in 60.0% and 40.0% of the group A and 27.3% and 62.7% of the group C.Conclusion. MII-pH study must be reserved to patients younger than 2-year old (high probability of weakly acid reflux) and children with atypical symptoms.

Fertility problems will arise in about 20% of adolescents with varicocele. (level of evidence: 1). The recommended indication criteria for varicocelectomy in children and adolescents are the following: varicocele associated with a small testis, additional testicular condition affecting fertility, bilateral palpable varicocele, pathological sperm quality (in adolescents older than16 years of age), varicocele associated with a supranormal response to LHRH stimulation test, symptomatic varicocele. Repair of a large varicocele physically or psychologically causing discomfort may be also considered.The aim of this multicenter study is to evaluate the management and treatment of varicocele in different Pediatric Surgery Centers throughout Italy by means of a questionnaire regarding varicocele diagnosis, treatment and follow-up.The management of varicocele in the study centers complied with the international guidelines in more than 80% of cases; The preoperative work-up was completed in 95% of cases; postoperative follow-up was at 18 months in 45% of cases, at least at 6 months after surgery in the remaining cases. Laparoscopic treatment had less relapses (independently from the technique used) respect to other techniques but there are no difference respect to hydrocele formation or persistence.

Peripheral arterial disease (PAD) is a common circulatory problem. In 2010 almost 18 million U.S. citizens suffered from PAD. Reflecting the aging population this number is projected to increase to 21 million by 2020. Critical limb ischemia (CLI), the most severe and deadly form of the disease, currently afflicts 2.8 to 3.5 million of those with PAD. By 2020, the U.S.prevalence of CLI is forecast to grow to between 3.6 and 4.5 million. Among PAD patients,about 1-3% will develop CLI [1].

Posterior urethral hemangioma (PUH) is a rare congenital lesion, included in group of polypoid or papillary lesion of the prostatic urethra. This lesion is responsible for a variety of symptoms in children that may be associated or isolated, sometimes its finding is occasional. The diagnosis is usually made by ultrasonography and cystourethrogram, but the gold standard is represented by the urethrocystoscopy with double possibility: diagnostic and therapeutic. The Authors report a case of 1-year-old boy with persisting haematuria, in whom a previews cystoscopy didn't find any cause of haematuria. An accurate urethrocystoscopy let to make diagnosis of prostatic urethral polyp, a transurethral resection was performed and pathological assessment confirmed the diagnosis of PUH.

BACKGROUND: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21. RESULTS: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis. CONCLUSIONS: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.

The aim of this study was to evaluate the effectiveness of a differential diagnostic approach to Hirshchsprung's Disease (HD) on the basis of age. Data on 185 consecutive children with suspected HD were subjected to an age-related diagnostic approach. The patients were divided into two groups according to age (A < 1 year; B > 1 year). Children in Group A had rectal suction biopsy (RSB) and contrast enema (CE), and in Group B anorectal manometry (ARM) was performed. Patients with a normal recto-anal inhibitory reflex (RAIR) underwent bowel disimpaction and medical treatment. Only selected cases in Group B underwent RSB and CE. In Group A (18 patients) CE showed a colonic transitional zone in three patients, whereas RSB led to the diagnosis of HD in nine. In Group B (167 patients) ARM was not possible in seven patients and it was normal in 140 (normal anal sphincter pressure: 83; hypertonia of the internal anal sphincter: 57). The RAIR was negative in 20 patients. RSB performed in 31 children in Group B confirmed HD in three patients. For patients with a neonatal onset of constipation RSB is the best diagnostic technique. Chronic constipation is rarely due to HD and ARM is a useful non-invasive screening tool. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.

Background/Purpose Isolated Fallopian tube torsion (IFTT) is a rare cause of acute abdominal pain in female. The preoperative diagnosis is difficult because of a lack of specific clinical and radiological signs. Surgery is often performed when is no longer possible to preserve the integrity of the tube. We report our experience in the laparoscopic management of four teenagers with IFTT. Methods Four patients (aged 12 to 15 years) came to our observation for worsening abdominal pain, nausea and vomit. At admission all girls had blood tests, ultrasound and Magnetic Resonance. Laparoscopy was performed in all cases for the diagnosis. All girls had US and clinic follow up. Results Laparoscopic exploration allowed the diagnosis of IFTT with necrosis of the same in all cases. In two girls a laparoscopic salpingectomy was performed. In the others two cases an open salpingectomy was necessary because of pelvic adhesions. Histology showed an hemorrhagic infarction of the fallopian tubes. At follow up all patients were asymptomatic with normal ovaries.

Bartholin gland cysts are one of the most common gynecologic problems. Around 2% of women suffer from these pathologies. Bartholin gland cyst are generally asymptomatic, but sometimes extremely painful to restrict physical activity. The treatment choice is related to the patient's age, the size of the cyst or abscess and relapses, but different approaches are possible. The aim of this study is to investigate the efficicacy and safety of the alcohol sclerotherapy versus the only aspiration to cure symptomatic cysts or abscesses of the Bartholin's gland.Between January 2002 and June 2004, 18 patients suffering from Bartholin symptomatic unilateral cysts or with abscess are selected. These patients have been divided into 2 groups and they have been treated with alcohol sclerotherapy or aspiration. The simple aspiration removes only the cyst fluid. The alcohol sclerotherapy allows to destroy the epithelial covering of the cyst by a coagulative necrosis and then a fibrosis which covers the cavity and prevents the reformation of liquid.Treatment has been satisfactory for all the patients, and treatment time has been shorter with alcohol sclerotherapy. None of the patients, in both groups, presented sexual dysfunctions or dyspareunia.Alcohol sclerotherapy might be an ideal and safe procedure in the treatment of the Bartholin's gland or abscesses with a low percentage of relapses.

The effect of nifedipine on fetal-placental blood flow at 22-24 weeks in patients with pregnancy-induced hypertension (PIH) was evaluated. Twenty patients with PIH were submitted to the Doppler evaluation of fetal-placental perfusion at 22-24 weeks. The systo-diastolic (SID) ratio and the pulsatility index (PI) of uterine, umbilical and middle cerebral arteries and systemic blood pressure were recorded before and 7 days after nifedipine administration (10 mg/ per os 3 times/day until delivery). Statistical analysis was performed with paired and unpaired t-test and the two-tailed Fisher exact test. Nifedipine significantly (p0.05) decreased the mean systolic pressure in all patients (from 146 to 135 mmHg): 8 patients developed pre-eclampsia (PE) complicated by fetal growth restriction (FGR) (PE group), whilst the remaining were only affected by PIH (PIH group). The gestational age at delivery, neonatal birthweight and 1- and 5-min Apgar scores were significantly (p0.001) lower in PE than in PIH women. Nifedipine treatment significantly changed the PI and S/D ratio (mean +/- SEM) of the uterine (PI from 0.66 +/- 0.01 to 0.51 + 0.01; SID ratio: from 2.00 +/- 0.09 to 1.79 + 0.05) and umbilical (PI: from 1.55 +/- 0.04 to 1.40 +/- 0.02; S/D ratio: from 2.45 +/- 0.09 to 2.31+/- 0.09) arteries and the middle cerebral PI (from 1.45 +/- 0.03 to 1.61 +/- 0.01) artery only in PIH, but not in PE patients. Fetal-placental blood flow changes after nifedipine may early identify patients at risk of PE.