RNA viruses and their silencing suppressors boost Abutilon mosaic virus, but not the Old World Tomato yellow leaf curl Sardinia virus

Mixed viral infections can induce different changes in symptom development, genome accumulation and tissue tropism. These issues were investigated for two phloem-limited begomoviruses, Abutilon mosaic virus (AbMV) and Tomato yellow leaf curl Sardinia virus (TYLCSV) in Nicotiana benthamiana plants doubly infected by either the potyvirus Cowpea aphid-borne mosaic virus (CABMV) or the tombusvirus Artichoke mottled crinkle virus (AMCV). Both RNA viruses induced an increase of the amount of AbMV, led to its occasional egress from the phloem and induced symptom aggravation, while the amount and tissue tropism of TYLCSV were almost unaffected. In transgenic plants expressing the silencing suppressors of CABMV (HC-Pro) or AMCV (P19), AbMV was supported to a much lesser extent than in the mixed infections, with the effect of CABMV HC-Pro being superior to that of AMCV P19. Neither of the silencing suppressors influenced TYLCSV accumulation. These results demonstrate that begomoviruses differentially respond to the invasion of other viruses and to silencing suppression.     

Octreotide LAR vs. surgery in newly diagnosed patients with acromegaly: a randomized, open-label, multicentre study

Objective  This prospective randomized study evaluated the efficacy and safety of octreotide LAR vs. surgery in newly diagnosed acromegalic patients.
Methods  Totally 104 male and female patients were enrolled in a 50-week, exploratory, open-label and randomized study. Eligible patients were randomized to receive either octreotide LAR 20 mg every 28 days or to undergo surgery. Efficacy was assessed by changes in mean GH and IGF-I serum concentrations, at weeks 12, 24 and 48. Tumour volume was assessed by contrast-enhanced MRI. In both groups, treatment adjustment was performed for patients uncontrolled at week 12 or 24. Octreotide LAR patients received a dose increased to 30 mg or, if already receiving this dose, investigator and patients could decide to cross-over to surgery. Patients uncontrolled after surgery received octreotide LAR 20 mg, increased to 30 mg if acromegaly was still uncontrolled.
Results  Overall success rates at weeks 24 and 48 were 25% and 28% for the octreotide LAR group and 49% and 39% for the surgery group. Only the difference observed at week 24 was statistically significant ( P =  0·047). Both groups had a significant (> 20%) tumour shrinkage: 73% of patients in the octreotide LAR group and 95% in the surgery group. Major differences between octreotide LAR and surgery group in the occurrence of adverse events were gastrointestinal (71% vs. 27%), hepatobiliary (41% vs. 8%) and respiratory (5% vs. 28%).
Conclusion  This first randomized study in unselected patients indicates that the 48-week treatment outcome of octreotide LAR as first-line treatment of acromegaly does not significantly differ from surgery. As a complete response to surgery in GH-secreting macro-adenomas can be difficult, first-line therapy with octreotide LAR can be considered as a viable alternative for most patients with acromegaly, due to its low complication rate.     

Cholestasis in neonatal intensive care unit: incidence, aetiology and management

Aim:  Prevalence, aetiology, management and outcome of cholestasis were evaluated in infants admitted to neonatal intensive care unit (NICU).
Methods:  Medical records of all infants admitted to two Italian level III NICUs from January 2005 to August 2007 were retrospectively reviewed. The role of ursodeoxycholic acid (UDCA) therapy was also investigated.
Results:  Twenty-seven of 1289 enrolled infants developed cholestasis. In 25 infants, cholestasis had a multifactorial basis, while in two, no aetiology was found. UDCA did not significantly affect clinical and biochemical course of cholestasis. During a period of 12 months, eight cholestatic infants died, one underwent liver transplantation and 18 fully recovered.
Conclusion:  Infants admitted in NICU have a rate of cholestasis higher than that reported in the general population of live births; in most cases, cholestasis is associated to multiple risk factors and shows a favourable outcome. UDCA does not seem to affect clinical course of cholestasis in this setting.     

IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis

Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non‐atopics. The aim of this study was to test the IL13 p.R130Q and c.1‐1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12–24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1‐1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen’s egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48–60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen’s egg. These findings suggest that IL13 variants play a major role not only in non‐cognate but also in allergen specific IgE synthesis.     

Muscle motion and EMG activity in vibration treatment

The aim of this study is to highlight the relationship between muscle motion, generated by whole body vibration, and the correspondent electromyographic (EMG) activity and to suggest a new method to customize the stimulation frequency. Simultaneous recordings of EMG and tri-axial accelerations of quadriceps rectus femoris from fifteen subjects undergoing vibration treatments were collected. Vibrations were delivered via a sinusoidal oscillating platform at different frequencies (10–45 Hz). Muscle motion was estimated by processing the accelerometer data. Large EMG motion artifacts were removed using sharp notch filters centred at the vibration frequency and its superior harmonics. EMG–RMS values were computed and analyzed before and after artifact suppression to assess muscular activity. Muscles acceleration amplitude increased with frequency. Muscle displacements revealed a mechanical resonant-like behaviour of the muscle. Resonance frequencies and dumping factors depended on subject. Moreover, RMS of artifact-free EMG was found well correlated (R² = 0.82) to the actual muscle displacement, while the maximum of the EMG response was found related to the mechanical resonance frequency of muscle.Results showed that maximum muscular activity was found in correspondence to the mechanical resonance of the muscle itself. Assuming the hypothesis that muscle activation is proportional to muscle displacement, treatment optimization (i.e. to choose the best stimulation frequency) could be obtained by simply monitoring local acceleration (resonance), leading to a more effective muscle stimulation. Motion artifact produced an overestimation of muscle activity, therefore its removal was essential.     

Redundant and Synergistic Mechanisms Control the Sequestration of Blood-born Adenovirus in the Liver

Human adenovirus (Ad) is a ubiquitous pathogen causing a wide range of diseases. Although the interactions of human Ad serotype 5 (Ad5) with susceptible cells in vitro are known in great detail, host factors controlling the tissue specificity of Ad5 infection in vivo remain poorly understood. Here, we analyzed the mechanisms of sequestration by the liver for blood-born human Ads and Ad5-based vectors. Our data suggest that several known mechanisms that lead to Ad5 sequestration by the liver become engaged in a redundant, sequential, and synergistic manner to ensure the rapid clearance of circulating virus particles from the blood. These mechanisms include (i) trapping of the virus by liver residential macrophages, Kupffer cells; (ii) Ad5 hepatocyte infection via blood factor–hexon interactions; and (iii) Ad5 penton RGD motif–mediated interactions with liver endothelial cells and hepatocytes, mediating virus retention in the space of Disse. More important, we show that when all of these mechanisms are simultaneously inactivated via mutations of Ad5 capsid proteins and pharmacological interventions, virus sequestration by the liver is markedly reduced. Therefore, our study is the first demonstration of the principal possibility of ablating the sequestration of blood-born Ad in the liver via specific inactivation of a defined set of mechanisms that control this process.     

A double-chamber rotating bioreactor for the development of tissue-engineered hollow organs: From concept to clinical trial

Cell and tissue engineering are now being translated into clinical organ replacement, offering alternatives to fight morbidity, organ shortages and ethico-social problems associated with allotransplantation. Central to the recent first successful use of stem cells to create an organ replacement in man was our development of a bioreactor environment. Critical design features were the abilities to drive the growth of two different cell types, to support 3D maturation, to maintain biomechanical and biological properties and to provide appropriate hydrodynamic stimuli and adequate mass transport. An analytical model was developed and applied to predict oxygen profiles in the bioreactor-cultured organ construct and in the culture media, comparing representative culture configurations and operating conditions. Autologous respiratory epithelial cells and mesenchymal stem cells (BMSCs, then differentiated into chondrocytes) were isolated, characterized and expanded. Both cell types were seeded and cultured onto a decellularized human donor tracheal matrix within the bioreactor. One year post-operatively, graft and patient are healthy, and biopsies confirm angiogenesis, viable epithelial cells and chondrocytes. Our rotating double-chamber bioreactor permits the efficient repopulation of a decellularized human matrix, a concept that can be applied clinically, as demonstrated by the successful tracheal transplantation.     

Arrhythmogenic right ventricular dysplasia/cardiomyopathy presenting as ST-segment elevation myocardial infarction: A case report

Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is often challenging due to differing clinical presentations and unpredictable progression of the disease. We report a case of ARVD/C that presented as cardiac arrest in an 18-year-old male while playing soccer. The electrocardiographic features after resuscitation were typical of anterior ST-segment elevation acute myocardial infarction, and the patient was initially managed accordingly. Importantly, an urgent coronary angiogram revealed completely normal coronary arteries. ARVD/C was first suspected following an echocardiogram, and was later confirmed by cardiac magnetic resonance. One month before the event, the patient had been evaluated for ventricular extrasystoles and an abnormal resting electrocardiogram, however ARVD/C was ruled out because of the presence of only two minor diagnostic criteria (T-wave inversion in anterior precordial leads in the absence of right bundle branch block and more than 1000 ventricular extrasystoles during 24-h Holter monitoring). In consequence, physical activity was not forbidden.In conclusion, this case report enforces the need for a strict prohibition of physical activity and serial evaluation of individuals with only minor diagnostic criteria for ARVD/C, for lacking sensibility of Task Force diagnostic criteria.     

Comparison of cytological features of myxopapillary ependymomas on crush preparations

Myxopapillary ependymoma (ME) is a rare neoplasm found predominantly in the sacro‐coccygeal region in adults and is characterized by its distinct epithelial and stromal components. From 1990 to April 2008, a total of 10 ME cases were recorded at our institution. Six out of 10 cases underwent frozen section examination with concomitant crush preparations, which forms the basis of this study. The clinical and cytologic findings in all six cases were reviewed. There were four males and two females. The age ranges from 15 to 36 years with a mean age of 27 years. The epithelial component of ME is strikingly similar for all six cases showing tumor cells appearing singly or in loose clusters, most with papillary branching. There was also presence of indistinct cell boundaries, tapered cytoplasmic prolongations, wispy/fragile cytoplasm, and uniform oval‐to‐fusiform shaped nuclei with an evenly distributed chromatin pattern. The stromal component was composed mainly of thick, metachromatic material and adenoid cystic‐like areas. One case showed rosette‐like structures. These aforementioned characteristics can be utilized to distinguish ME from other primary and metastatic tumors such as meningioma, adenoid cystic carcinoma, chordoma, mucinous adenocarcinoma, chondrosarcoma, and germ cell tumors. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.