Intestinal atresia and necrotizing enterocolitis: Embryology and anatomy.

The primitive gut originates at week 3 of gestation from the endoderm, with posterior incorporation of the remaining embryo layers. Wnt, Notch and TLR4 pathways have been shown to play central roles in the correct development of the intestine. The classical hypothesis for intestinal atresia development consists of failure in bowel recanalization or a vascular accident with secondary bowel reabsorption. These have been challenged due to the high frequency of associated malformations, and furthermore, with the discovery of molecular pathways and genes involved in bowel formation and correlated defects producing atresia. Necrotizing enterocolitis (NEC) has a multifactorial pathogenesis with prematurity being the most important risk factor; therefore, bowel immaturity plays a central role in NEC. Some of the same molecular pathways involved in gut maturation have been found to correlate with the predisposition of the immature bowel to develop the pathological findings seen in NEC.

Nitroxide spin labels and EPR spectroscopy: A powerful association for protein dynamics studies.

Site-Directed Spin Labelling (SDSL) technique is based on the attachment of a paramagnetic label onto a specific position of a protein (or other bio-molecules) and the subsequent study by Electron Paramagnetic Resonance (EPR) spectroscopy. In particular, continuous-wave EPR (cw-EPR) spectra can detect the local conformational dynamics for proteins under various conditions. Moreover, pulse-EPR experiments on doubly spin-labelled proteins allow measuring distances between spin centres in the 1.5-8 nm range, providing information about structures and functions. This review focuses on SDSL-EPR spectroscopy as a structural biology tool to investigate proteins using nitroxide labels. The versatility of this spectroscopic approach for protein structural characterization has been demonstrated through the choice of recent studies. The main aim is to provide a general overview of the technique, particularly for non-experts, to spread the applicability of this technique in various fields of structural biology.

Multiparametric MR imaging of the prostate at 1.5-T without endorectal coil using an 8 channel pelvic phased array: Is it still a viable option?

INTRODUCTION: The purpose of our work was to evaluate the feasibility of prostate multiparametric MR imaging at 1.5-T without endorectal coil using an 8 channel pelvic phased array coil. MATERIAL AND METHODS: A total of 154 patients who underwent mp-MRI were retrospectively included. Patients received a standardized mp-MRI, compliant with 2012 European Society of Uro-Radiology guidelines, with 1·5 T magnetic field strength and an 8 channel pelvic phased-array coil. Two blinded readers graded the image quality of mp-MRI on a three-point scale and they scored the prostate lesions according to PI-RADS v2. All PI-RADS of 4 or 5 underwent biopsy. A third radiologist and a pathologist verified the correspondence between the MRI images and the results of the biopsy. RESULTS: 64 (41.6%) patients showed a Pi-rads of 4 or 5. At biopsy, 79.7% showed a Gleason score ≥7, 12.5% showed a Gleason score of 6 and 7.8% showed a negative biopsy. In the group of Pi-rads ≤ 3, 12 patients underwent a biopsy with the following results: negative biopsy in 33.3%, atypical Small Acinar Proliferation in 16.7%, prostatic intraepithelial neoplasia in 25% and indolent PCa 25%. Mp-MRI in the identification of clinically significant cancer provided a low percentage of false positive (7.8%) while in 79.7% of cases it was capable to detect clinically significant prostate cancer. In 92.2% of patients mp-MRI identified a prostate cancer with a Gleason score ≥6. The inter-reader agreement was excellent in defining both the quality of the examination and the PI-RADS category (k = 0.83 and k = 0.70, respectively). CONCLUSIONS: mp-MRI at 1.5-T without endorectal coil using an 8 channel phased array is an appropriate tool for early detection of clinically significant prostate cancer. IMPLICATIONS FOR PRACTICE: 8 channel pelvic phased array is still an appropriate tool for early detection of clinically significant prostate cancer and for obtaining a reduction in overdiagnosis of indolent PCa.

Depression risk among patients with chronic wounds.

OBJECTIVE: A wound is defined as chronic when it requires more than 6 weeks to heal. The link between chronic wounds and depression was first pointed out by House and Hughes in 1996 and later evaluated by other numerous studies. Several studies demonstrate that among chronic skin wounds causing chronical physical disease, the leg ulcers are the most frequently associated with depression. The aim of our study is to evaluate the prevalence of depression in patients with different types of chronic wounds. PATIENTS AND METHODS: We enrolled a total of 33 patients with chronic wounds and 33 healthy controls matched by sex and age. Both patients and controls underwent a BDI II survey. We evaluated 33 patients, with a mean age of 71 years (range 25-87), and 33 controls, with a mean age of 73 years (range 31-88). RESULTS: The average score at the BDI II questionnaire was 14.5 and 8, respectively. CONCLUSIONS: The depression among patients with chronic wounds has a multifactorial origin that should be treated with a multidisciplinary approach. Since the improvement of the psycho-emotional state means better compliance of the patient, we can also expect a better result in terms of efficacy in chronic wound treatment.

ECG-gated CT angiography of the thoracic aorta: the importance of evaluating the coronary arteries.

AIM: To evaluate the feasibility of coronary artery disease (CAD) evaluation using electrocardiogram-gated computed tomography CT of the thoracic aorta. MATERIALS AND METHODS: A total of 477 patients, who underwent CT angiography of the thoracic aorta, were included retrospectively. Dose-length products (DLP) were recorded. Two blinded readers graded image quality of the coronary arteries on a three-point scale. Coronary artery stenosis has only been reported if considered significant, i.e., ≥50%. The type of plaque responsible for the stenosis was considered. The normal distribution of the data was assessed using Shapiro-Wilk and Anderson-Darling tests. Results were expressed as means and standard deviations and percentages. Inter-reader agreements were analysed by calculating the intraclass correlation coefficient, and by using Cohen kappa statistics. RESULTS: The mean DLP was 566±90.4 mGy∙cm, corresponding to an effective dose of 9.6±1.5 mSv. Five point three percent of asymptomatic patients were positive for CAD with stenosis ≥50%. All patients with coronary stenosis presented with a soft plaque. Two anomalous coronary origins were found. The inter-reader agreement was excellent in defining both the quality of the examination and the degree of coronary stenosis (k=0.85). CONCLUSION: The opportunity to prove the presence of CAD in asymptomatic patients during a ECG-gated CT of the thoracic aorta can have an extremely important clinical impact, promoting the best therapeutic pathway for the patient. Therefore, coronary arteries should always be analysed carefully and reported in ECG-gated CT angiography of the thoracic aorta.

Double-blind randomized clinical trial of percutaneous endoscopic gastrostomy versus radiologically inserted gastrostomy in children.

BACKGROUND: The aim of this RCT was to determine whether radiologically inserted gastrostomy (RIG) in children is associated with more complications than percutaneous endoscopic gastrostomy (PEG). METHODS: Children at a single tertiary children's hospital requiring a primary gastrostomy were randomized to PEG or RIG. Patients were followed by assessors blinded to the insertion method. Complications were recorded, assigned a severity score, and analysed by zero-inflated Poisson regression analysis on an intention-to-treat basis, adjusting for length of follow-up. RESULTS: Over a 3-year period, 214 children were randomized (PEG, 107; RIG, 107), of whom 100 received PEG and 96 RIG. There was no significant difference in the number of complications between PEG and RIG groups (P = 0·875), or in the complication score: patients undergoing RIG had a 1·04 (95 per cent c.i. 0·89 to 1·21) times higher complication score than those who underwent PEG (P = 0·597). Only age had an independent significant effect on complication score, with older patients having a 0·97 (0·95 to 1·00) times lower complication score per year. CONCLUSION: PEG and RIG are both safe methods of gastrostomy insertion with a low rate of major complications. Registration number: NCT01920438 ( http://www.clinicaltrials.gov).

Characterization of antibody response in neuroinvasive infection caused by Toscana virus.

OBJECTIVES: Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy. METHODS: Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies. RESULTS: Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG. CONCLUSIONS: Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation.

MR-enterography with diffusion weighted imaging: ADC values in normal and pathological bowel loops, a possible threshold ADC value to differentiate active from inactive Crohn's disease.

OBJECTIVE: The aim of our study was to compare the apparent diffusion coefficient (ADC) values of pathological bowel loops wall (pADC) with the ADC values of normal appearing ones (naADC) and to determine a discriminating threshold. PATIENTS AND METHODS: 60 patients were studied at our Institution through a MR-enterography that included free-breathing axial Diffusion Weighted Imaging (DWI) with two b (0 and 800 s/mm2) after histological diagnosis of active Crohn's disease (CD). The one (when unique) or the best analyzable (when multiple) pathological bowel loop was identified in each patient, on the basis of the MRI features: wall thickness, presence of mural oedema and wall contrast enhancement after contrast medium administration. A normal appearing bowel loop was used for comparison. ADC values were measured in consensus by two radiologists, and they were compared with t-test. The ADC threshold value for the differentiation between pathological and normal appearing bowel loops was determined. RESULTS: The pADC values were significantly lower than the naADC values (1.48 ± 0.058 x 10-3 mm2/s versus 3.525 ± 0.07 x 10-3 mm2/s; p < 0.05). A threshold of 2.416 x 10-3 mm2/s showed 100% sensitivity and 100% specificity for the discrimination between normal and pathological bowel loops. CONCLUSIONS: In patients with active CD the ADC values of the pathological bowel wall are significantly lower than those of normal appearing bowel loops. A threshold of ADC value of 2.416 10-3 mm2/s could discriminate normal from pathological bowel loops.

Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis.

PURPOSE: Feeding and systemic hypoxia are major stresses inducing necrotizing enterocolitis (NEC). This study aims to investigate the role of systemic hypoxia in NEC and its effect before and after feeding. METHODS: Neonatal mice were studied in three groups. Control (N = 9): breast feeding; NEC A (N = 8), gavage feeding + lipopolysaccharide (LPS) + preprandial hypoxia; and NEC B (N = 9), feeding + LPS + postprandial hypoxia. Pimonidazole, a hypoxia marker, was injected intraperitoneally before ileum was harvested for histology and quantitative RT-PCR studies. Statistical analysis was done using the ANOVA and Chi-square test. RESULTS: NEC incidence was 62.5% in NEC A and 88.9% in NEC B. The mortality in NEC B (55.6%) but not A (25%) is significantly higher than control (0%, p < 0.05). Pimonidazole staining elevated in both NEC A and B with higher pimonidazole grade in NEC B (p < 0.01). Both NEC groups had increased the expression of hypoxia-related genes: HIF-1α, GLUT-1, and PHD-3 with GLUT-1 expressed more in NEC B compared with NEC A (p < 0.01). The inflammation marker, IL6, was similarly raised in both NEC A and B. CONCLUSION: Feeding and postprandial hypoxia synergistically induce intestinal hypoxia in NEC. As feeding increases intestinal oxygen demand, maintaining a balance between intestinal oxygen supply and demand is important to prevent NEC.

Umbilical hernia following gastroschisis closure: a common event?

PURPOSE: To assess incidence and natural history of umbilical hernia following sutured and sutureless gastroschisis closure. METHODS: With audit approval, we undertook a retrospective clinical record review of all gastroschisis closures in our institution (2007-2013). Patient demographics, gastroschisis closure method and umbilical hernia occurrence were recorded. Data, presented as median (range), underwent appropriate statistical analysis. RESULTS: Fifty-three patients were identified, gestation 36 weeks (31-38), birth weight 2.39 kg (1-3.52) and 23 (43 %) were male. Fourteen patients (26 %) underwent sutureless closure: 12 primary, 2 staged; and 39 (74 %) sutured closure: 19 primary, 20 staged. Sutured closure was interrupted sutures in 24 patients, 11 pursestring and 4 not specified. Fifty patients were followed-up over 53 months (10-101) and 22 (44 %) developed umbilical hernias. There was a significantly greater hernia incidence following sutureless closure (p = 0.0002). In sutured closure, pursestring technique had the highest hernia rate (64 %). Seven patients underwent operative hernia closure; three secondary to another procedure. Seven patients had their hernias resolve. One patient was lost to follow-up and seven remain under observation with no reported complications. CONCLUSIONS: There is a significant umbilical hernia incidence following sutureless and pursestring sutured gastroschisis closure. This has not led to complications and the majority have not undergone repair.

Three-year retrospective analysis of the incidence of Toxoplasma gondii infection in pregnant women living in the Greater Romagna Area (northeastern Italy).

The aim of this study was to assess the incidence of Toxoplasma gondii infection in a population of pregnant women living in the Romagna area of the Emilia-Romagna region. From 1 January 2012 to 31 December 2014, 36 876 pregnant women were tested to evaluate the IgG- and IgM-specific anti-T. gondii response. The average incidence was 0.192%, underlining the need for an appropriate and active screening for toxoplasmosis during pregnancy.

Running away from stress: How regulatory modes prospectively affect athletes' stress through passion.

A prospective field study conducted with runners training for an upcoming marathon (Marathon of Rome 2013) examined the relation between regulatory modes, locomotion and assessment, and stress. Integrating regulatory mode theory and the dualistic model of passion, we hypothesized that the relation between regulatory modes (evaluated 3 months before the race) and the experience of stress approaching the marathon, is mediated by the type of passion (harmonious vs obsessive) athletes experience with regard to marathoning. Results revealed that (a) locomotion positively predicted harmonious passion, which in turn reduced athletes' experience of stress; and (b) assessment positively predicted obsessive passion, which in turn enhanced athletes' experience of stress. Overall, the present results suggest that proximal psychological mechanisms such as basic regulatory mode orientations can predict distal outcomes such as stress indirectly through their relation with motivational phenomena such as passion.

Persistence of anti-chikungunya virus-specific antibodies in a cohort of patients followed from the acute phase of infection after the 2007 outbreak in Italy.

Chikungunya is a mosquito-borne infection of humans, and its diffusion has increased worldwide. In 2007 an outbreak occurred in Italy. In this study, the antibody response of 133 patients followed up starting from the acute phase of infection was investigated. Antibody titres were periodically scored up to 1 year since the infection: 82.7% of the IgM antibody disappeared within 12 months, and the IgG response lasted longer than 12 months. Nevertheless, the IgG mean titre was lower in 95.5% of patients at the end of follow-up, thus suggesting a decrease within a relatively short period.

Esophageal atresia and malrotation: what association?

INTRODUCTION: Esophageal atresia/tracheo-esophageal fistula (EA/TEF) has an incidence of approximately 1:3,500. The incidence of malrotation is thought to be 1:200-500. We attempted to define the incidence of a combination and discuss the implications. METHODS: This was a retrospective review of all patients admitted to a single institution with a diagnosis of EA or EA/TEF or TEF between April 1981 and January 2013. Patients were included if the position of the duodeno-jejunal flexure (DJF) was determined by upper GI contrast study (UGIS), surgery or post-mortem. RESULTS: Case notes were reviewed for 235 patients. In the EA type A group, 3/28 (11 %; 95 % CI 3.7-27.2 %) had malrotation, significantly higher than the reported incidence of malrotation in the general population (p = 0.0008). All three patients in this group were symptomatic with one patient found to have a volvulus at emergency surgery. In the type C group, 6/196 (3 %, 95 % CI 1.4-6.5 %) had malrotation, significantly higher than the incidence reported for the general population (p = 0.0033) but not significantly different to that of the type A group (p = 0.0878). There were no patients with malrotation identified in any other EA/TEF type. In total, 9/235 (3.8 %; 95 % CI 2.0-7.2 %) patients with EA had malrotation, significantly higher than the 5/1,050 (0.48 %) reported for the general population (p = 0.0002). CONCLUSION: There is a high incidence of malrotation in patients with pure EA. In the type A group an attempt to identify the DJF position at gastrostomy siting and/or performance of UGIS in the neonatal period should be undertaken. There should also be a low threshold for UGIS in all EA/TEF patients.

Human and entomological surveillance of Toscana virus in the Emilia-Romagna region, Italy, 2010 to 2012.

Toscana virus (TOSV), transmitted by phlebotomine sandflies, is recognised as one of the most important causes of viral meningitis in summer in Mediterranean countries. A surveillance plan based on both human and entomological surveys was started in 2010 in the Emilia-Romagna region, Italy. Clinical samples from patients with neurological manifestations were collected during 2010 to 2012. The surveillance protocol was improved during these years, allowing the detection of 65 human infections. Most of these infections were recorded in hilly areas, where sandflies reach the highest density. Entomological sampling around the homes of the patients resulted in a low number of captured sandflies, while later sampling in a hilly area with high number of human cases (n=21) resulted in a larger number of captured sandflies. Using this approach, 25,653 sandflies were sampled, of which there were 21,157 females, which were sorted into 287 pools. TOSV RNA was detected by real-time PCR in 33 of the pools. The results highlighted the role of Phlebotomus perfiliewi as the main vector of TOSV and a potential link between vector density and virus circulation. This integrated system shows that an interdisciplinary approach improves the sensitiveness and effectiveness of health surveillance.

A model of laboratory surveillance for neuro-arbovirosis applied during 2012 in the Emilia-Romagna region, Italy.

Arboviruses with neuroinvasive potential are gaining more attention due to the increased number of cases of autochthonous and imported infections in the human host. Diagnosis of infection caused by these viruses in patients with central nervous system (CNS) diseases is still underestimated and these infections represent an emerging threat to public health. We describe a model suitable for the laboratory surveillance of neuro-arbovirosis that was applied in the Emilia-Romagna region, north-eastern Italy, during the 2012 summer season. One hundred and twenty cases of suspected neuroinvasive infection were tested for arboviral agents on the basis of clinical and laboratory signs and epidemiological data. The most common virus detected was Toscana virus (TOSV): anti-TOSV specific antibodies or viral components were detected in 28.3% of the cases; 79.4% of the TOSV cases were in the acute phase of infection. No cases resulted in acute phase for West Nile (WNV), Usutu (USUV), Chikungunya (CHIKV) or Dengue (DENV) virus infection. Conversely, two patients with a history of staying in a tick-borne encephalitis virus (TBEV) endemic area showed a probable TBEV infection. These results emphasize the importance of a complete and 'ready to act' laboratory diagnostic system to be implemented within the larger frame of a regional integrated surveillance system.

Detection of specific antibodies against West Nile and Usutu viruses in healthy blood donors in northern Italy, 2010-2011.

Neutralizing antibodies against West Nile (WNV) and Usutu (USUV) viruses were measured in 6000 samples collected, between 1 September 2010 and 30 June 2011, from blood donors living in different districts of Emilia-Romagna, northeastern Italy. On the basis of the microneutralization assay (MNTA), 47 (0.78%) subjects were positive for WNV and 14 (0.23%) for USUV. These results were compared with those obtained 2 years ago and suggest an increased circulation of USUV among humans in Emilia-Romagna.

West Nile virus in Europe: emergence, epidemiology, diagnosis, treatment, and prevention.

West Nile virus (WNV), a mosquito-borne flavivirus in the Japanese encephalitis antigenic group, has caused sporadic outbreaks in humans, horses and birds throughout many of the warmer regions of Europe for at least 20 years. Occasional cases of West Nile encephalitis have also been associated with infected blood transfusions and organ donations. Currently, WNV appears to be expanding its geographical range in Europe and causing increasing numbers of epidemics/outbreaks associated with human morbidity and mortality. This brief review reports on the current epidemic situation regarding WNV in Europe, highlighting the clinical, diagnostic and preventive measures available for controlling this apparently emerging human pathogen.

Meckel's scan in children: a review of 183 cases referred to two paediatric surgery specialist centres over 18 years.

AIM: To review our practice of Meckel's Tc-99m pertechnetate scans over 18 years with regard to indications for the test, sensitivity and specificity in our particular referral patients' population. MATERIALS AND METHODS: This is a retrospective review of Meckel's scans performed in two paediatric tertiary care teaching hospitals from April 1993 to March 2011 and followed up till October 2011. The scan was performed according to published international guidelines. 183 patients were included in this study. We classified the patients into two groups: group 1, which included 77 patients (42 %) presenting with painless per rectum bleeding, and group 2, which included 106 patients (58 %) presenting with other non-specific symptoms (e.g. abdominal pain, possibly associated with nausea and/or vomiting, failure to thrive). Data were analysed using Chi square test, considering P value less than 0.05 as significant. The age of the patients ranged from 4 days to 16.5 years (median 3 years). RESULTS: 161 of the total 183 children on the study (88 %) had a negative Meckel's scan, and 22 children (12 %) had a positive scan. In the group with a positive Meckel's scan (22 children), all patients underwent surgical exploration and ectopic gastric mucosa was found in 17 cases (77 %, true positives). In the remaining 5 cases (23 %), there was no evidence of ectopic gastric mucosa (false positives). Within the group with a negative scan, 8 children (5 %) underwent surgery; only 1 child had a ectopic gastric mucosa detected following surgery (false negative). In other 52 children (32 %) of the group with a negative Meckel's scan, an endoscopy was done, which showed a normal result in 21 children and was abnormal in 31 children. Of the remaining 101 (63 %) children with a negative Meckel's scan, 74 children (46 %) improved without any further intervention. In 13 cases (8 %), other pathologies were identified. The sensitivity and specificity of the Meckel's scan for ectopic gastric mucosa were 94 and 97 %, respectively. The Meckel's scan was positive in 26 % of the patients of group 1 and in only 2 % patients of group 2. The difference between the two groups was highly significant [P < 0.0001 (Yates-corrected Chi square); odds ratio 18 (Woolf-logit method 95 % CI)]. CONCLUSION: The Meckel's scan retains a high diagnostic accuracy in children for detecting a Meckel's diverticulum with ectopic gastric mucosa within it, when performed according to the recommended guidelines. The test yields its highest positive result in children presenting with significant per rectum bleeding.