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There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS).MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment.Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing.The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness.BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.

Purpose The purpose of this study was to assess the ability of 2 commonly used knee braces to control knee valgus motion and subsequent strain on the medial collateral ligament (MCL) in a laboratory-controlled environment. Methods Twenty healthy individuals (6 male, 14 female; mean age, 23 ± 3 years) with no history of knee injury or brace use performed a jump landing task while wearing either no brace or 1 of 2 braces: the Playmaker and Total Range of Motion . Three-dimensional joint kinematics and kinetics were measured in our biomechanics laboratory. Results Significantly less knee dynamic valgus angulation was noted when using either brace (−0.51° ± 3.9° and −1.3° ± 3.2°) compared no brace (4.8° ± 3.0°). Dynamic valgus angulation did not differ significantly between the 2 braces tested, which were both not statistically different from baseline alignment. There were significant differences seen in peak knee flexion angle between each brace (77.9° ± 8.8°and 83.1° ± 8.4°), as well as between both braces and no brace (90.6° ± 11.1°). There was no significant difference in knee frontal plane moment or peak vertical ground reaction force loading among all 3 testing conditions. Conclusions Compared to no brace, both braces allowed significantly less dynamic valgus angulation of the knee under physiological vertical loads but were not significantly different from one another. Clinical Relevance Knee braces are commonly used to protect the MCL when placed under physiological loads. It is important to know which braces effectively reduce valgus stress to provide the best outcomes.

Background Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self-expanding metal stents (SEMS) have been increasingly used as a bridge-to-surgery (BTS) strategy. Materials and methods In an 8-year period, consecutive patients with acute left-sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease-free survival (DFS) of the two therapeutic options. Results Forty-five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil-lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43-0.98, P = .04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P = .33) and DFS (36 in SEMS; 35 in ES, P = .35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4-16.6, P = .04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08-50, P = .04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16-0.92, P = .03). At multivariate analysis, no feature retained an independent predictive power. Conclusion SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients.

To identify the prevalence and risk factors of depression among individuals given a glaucoma-related diagnosis at a screening program.Cross-sectional community-based in a university hospital.Volunteers from a community glaucoma-screening program.After collecting sociodemographic information, participants were administered the Geriatric Depression Scale-15 (GDS-15) and the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25).Participants were predominantly African American (73.5%), older than 65 years (65.7%), single (75.4%), and female (66.8%). Among 268 participants, 89 were diagnosed with glaucoma and 179 as glaucoma suspects. The frequency of depression among the glaucoma and glaucoma suspect participants was 18% and 16.2%, respectively. The mean GDS-15 score was 2.4 ± 2.7 with no difference between glaucoma and glaucoma suspect groups, p = 0.654. The mean VFQ-25 score was 78.6 ± 15.9 and was lower in glaucoma (74.7 ± 19.7) than glaucoma suspect participants (80.4 ± 13.6), p = 0.003. Risk factors for depression included difficulties with paying expenses (p = 0.017), Asian race (p0.001), and poorer scores on the VFQ-25 subscales of "General Health" (p0.001), "Distance Activities" (p = 0.024), and "Dependency" (p = 0.001).Prevalence of depression in those diagnosed with glaucoma or glaucoma suspect was higher than previous estimates of the general population. Glaucoma-screening programs might benefit from including depression-screening protocols along with referral services or low-cost treatments of depression.

Inverted colonic diverticulum (ICD) is a rare intraluminal lesion occurring in about 0.7-1.7% of people, often endoscopically indistinguishable from polyps. Some unspecific endoscopic features may assist to distinguish polypoid ICD from true polyps. This differentiation bears relevance for the therapeutic approach, as colonic polyps require snare polypectomy, a practice which may be associated with colonic perforation in case of true ICD. The endoscopist, therefore, should be aware of the likelihood of detecting these lesions during colonoscopy. A close inspection and a gentle probing could assist in a correct diagnosis and avoid risky procedures such as biopsy or polypectomy. Rarely, a neoplasm arising over an ICD and its treatment has been described. We reported two cases, one of which with dysplasia, and their treatment, and reviewed all the ICD endoscopic cases so far reported in the literature, remarking the possibility of finding pedunculated ICDs or neoplasm arising over an ICD.

BACKGROUND: The purpose of this study was to examine the cost differences between preoperative and postoperative placement of gastrostomy tubes (G-tubes) in patients with head and neck cancer. METHODS: We conducted a retrospective chart review of patients with aerodigestive tract cancers from 2010 to 2015. Data included inpatient and postdischarge costs, demographics, tumor characteristics, surgical treatment, length of stay (LOS), time spent in the intensive care unit (ICU), and readmissions. RESULTS: Five hundred ninety patients were included in this study. There was a $7624 inpatient cost savings (P = .002) for those G-tubes placed preoperatively ($26 060) versus postoperatively ($33 754). Postdischarge costs did not differ significantly between groups (P = .60). There was a $9248 total costs savings (P = .009) for those patients with G-tubes placed preoperatively ($39 751) versus postoperatively ($48 999), despite patients with preoperative G-tubes having lower body mass index (BMI; P = .009), higher Association of Anesthesiologist (ASA) class (P = .02), more preoperative radiation (P < .001), and more free tissue transfer reconstruction (P = .007). CONCLUSION: There is potential for savings by placing G-tubes preoperatively, possibly driven by decreased LOS, despite data suggesting that patients with G-tubes placed preoperatively are higher risk.

Resume Introduction La conference des Nations Unies pour les changements climatiques (COP21) a reuni en France des delegations venues du monde entier, avec chaque jour 20 000 delegues de 195 pays dont 150 chefs d’etat lors des 48 premieres heures. Un dispositif medical specifique a ete organise dans un contexte particulier « post-attentats » et avec des contraintes fortes dues a la creation d’une zone sous l’unique autorite de l’ONU (zone bleue). Objectif Dresser le bilan des moyens medicaux engages et des soins dispenses. Methodes Dispositif medical gere par le Samu 93 en collaboration avec le Samu zonal et l’Agence regionale de sante (ARS) pour tout le site dont la zone bleue. Criteres de jugement : effectifs engages, nombre de consultations, d’evacuations dont evacuations medicalisees. Resultats En « zone France » (poste de commandement operationnel) : un medecin regulateur et un assistant pendant 20 jours. En « zone bleue » : 20 secouristes, une equipe medicale (Smur) H24 et deux medecins urgentistes (consultations) 12/24 heures pendant 16 jours. Au total, 47 medecins, 25 infirmiers, 25 ambulanciers Smur, 20 assistants ont participe au dispositif medical. Ceci correspondait a trois equivalents temps plein (ETP) medical d’urgentiste pendant 16 jours. Consultations realisees : 1238 soit 97/j resultant en 34 (3 %) evacuations dont sept medicalisees. Les patients etaient 706 (57 %) hommes et 495 (43 %) femmes, d’âge moyen 43 ± 1 an. La traumatologie predominait (20 %). Conclusion Les moyens medicaux engages etaient consequents pendant 16 jours. L’activite medicale etait soutenue, mais une evacuation medicalisee rarement requise.

Viral infection is an ongoing challenge to bacterial survival, and there is strong selection for development or acquisition of defense systems that promote survival when bacteria are attacked by bacteriophages. Temperate phages play central roles in these dynamics through lysogenic expression of genes that defend against phage attack, including those unrelated to the prophage. Few prophage-mediated viral defense systems have been characterized, but they are likely widespread both in phage genomes and in the prophages integrated in bacterial chromosomes., The arms race between bacteria and their bacteriophages profoundly influences microbial evolution. With an estimated 1023 phage infections occurring per second, there is strong selection for both bacterial survival and phage coevolution for continued propagation. Many phage resistance systems, including restriction-modification systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) systems, a variety of abortive infection systems, and many others that are not yet mechanistically defined, have been described. Temperate bacteriophages are common and form stable lysogens that are immune to superinfection by the same or closely related phages. However, temperate phages collude with their hosts to confer defense against genomically distinct phages, to the mutual benefit of the bacterial host and the prophage. Prophage-mediated viral systems have been described in Mycobacterium phages and Pseudomonas phages but are predicted to be widespread throughout the microbial world. Here we describe a new viral defense system in which the mycobacteriophage Sbash prophage colludes with its Mycobacterium smegmatis host to confer highly specific defense against infection by the unrelated mycobacteriophage Crossroads. Sbash genes 30 and 31 are lysogenically expressed and are necessary and sufficient to confer defense against Crossroads but do not defend against any of the closely related phages grouped in subcluster L2. The mapping of Crossroads defense escape mutants shows that genes 132 and 141 are involved in recognition by the Sbash defense system and are proposed to activate a loss in membrane potential mediated by Sbash gp30 and gp31.

Chromatin structure and its organization contributes to the proper regulation and timing of DNA replication. Yet, the precise mechanism by which chromatin contributes to DNA replication remains incompletely understood. This is particularly true for cell types that rely on polyploidization as a developmental strategy for growth and high biosynthetic capacity. During Drosophila larval development, cells of the salivary gland undergo endoreplication, repetitive rounds of DNA synthesis without intervening cell division, resulting in ploidy values of ~1350C. S phase of these endocycles displays a reproducible pattern of early and late replicating regions of the genome resulting from the activity of the same replication initiation factors that are used in diploid cells. However, unlike diploid cells, the latest replicating regions of polyploid salivary gland genomes, composed primarily of pericentric heterochromatic enriched in H3K9 methylation, are not replicated each endocycle, resulting in under-replicated domains with reduced ploidy. Here, we employ a histone gene replacement strategy in Drosophila to demonstrate that mutation of a histone residue important for heterochromatin organization and function (H3K9) but not mutation of a histone residue important for euchromatin function (H4K16), disrupts proper endoreplication in Drosophila salivary gland polyploid genomes thereby leading to DNA copy gain in pericentric heterochromatin. These findings reveal that H3K9 is necessary for normal levels of under-replication of pericentric heterochromatin and suggest that under-replication at pericentric heterochromatin is mediated through H3K9 methylation.

In this paper we try for the first time to shed light on the use of Twitter by the Italian speaking users quantifying the total audience and some relevant characteristics: in particular, gender and location. The attempt is based on publicly available APIs data referring both to profile documents and tweets. Through real-time calculation is possible to infer the gender mainly using the name field of the users’ profile, while the geo-location is deduced using the location field and the geotagged tweets.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor originating from perivascular epitheloid cells showing melanocytic and smooth muscle differentiation. The uterus represents the second most common site of origin. A 49 years woman presented to our Hospital for a vaginal spontaneous expulsion of a mass suggestive for malignant mesenchymal tumor. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy and the histopathological report was compliant with a PEComa with aggressive behavior. Medical Literature databases about PEComa were searched. The current literature identified near 90 cases of uterine PEComas and they are categorized as uncertain malignant potential or with aggressive behavior. Primary surgical excision represents the gold-standard treatment. Recently targeted therapy with mTOR inhibitors has been introduced with an important beneficial. In this paper we review the Literature about the uPEComa with aggressive behavior reporting the first case of spontaneous vaginal expulsion.

Extrinsic approaches for the pursuit of ductility in metallic glasses have involved the introduction of a ductile crystalline phase to inhibit the propagation of a dominant shear front through the amorphous matrix material. Using nanoindentation, we explore the role of crystalline inclusions in metallic glass matrix composites with a focus on the onset of shear banding in the amorphous matrix and the nature of shear band propagation using the propensity for localization and its dependence on indentation strain rate. When indentation length scales are favorable to distribute strain to both the crystalline dendrites and amorphous matrix, we reveal a reduction in the number of detectable displacement bursts and an accompanying decrease in the magnitude of individual depth excursions from shear banding. A decrease in the stress at the onset of shear banding is also correlated with shear band trajectories interacting with the amorphous-crystalline interfaces (ACIs). Our results thus demonstrate that ACIs reducing the activation barrier for shear banding combined with dendrites arresting propagating shear fronts act to enhance the nucleation rate and in turn, promote a more homogeneous plastic response.

Background In neonatal endotracheal intubation, excessive pressure on soft tissues during laryngoscopy can determine permanent injury. Low-fidelity skill trainers do not give valid feedback about this issue. This study describes the technical realization and validation of an active neonatal intubation skill trainer providing objective feedback. Methods We studied expert health professionals’ performances in neonatal intubation, underlining chance for procedure retraining. We identified the most critical points in epiglottis and dental arches and fixed commercial force sensors on chosen points on a ©Laerdal Neonatal Intubation Trainer. Our skill trainer was set up as a grade 3 on Cormack and Lehane’s scale, i.e. a model of difficult intubation. An associated software provided real time sound feedback if pressure during laryngoscopy exceeded an established threshold. Pressure data were recorded in a database, for subsequent analysis with non-parametric statistical tests. We organized our study in two intubation sessions (5 attempts each one) for everyone of our participants, held 24 h apart. Between the two sessions, a debriefing phase took place. In addition, we gave our participants two interview, one at the beginning and one at the end of the study, to get information about our subjects and to have feedback about our design. Results We obtained statistical significant differences between consecutive attempts, with evidence of learning trends. Pressure on critical points was significantly lower during the second session (p

Recent reports suggest that maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) may predict perinatal outcome. PAPP-A is a syncytiotrophoblast derived protease for insulin-like growth factor binding protein (IGFBP4); its protease activity cleaves complexed growth factor binding protein increasing insulin-like growth factor I (IGF-I) bioavailability. The aim of our study was to evaluate the correlation between maternal PAPP-A serum levels and neonatal growth. We analysed 100 full term and preterm (30 - 36 weeks) small for gestational age (SGA) and adequate for gestational age (AGA) babies whose mothers had been tested for serum PAPP-A at 11 - 13 weeks of gestation. We found a significant positive correlation between maternal PAPP-A and neonatal weight, length, and head circumference at birth in both term and preterm infants. Low maternal PAPP-A serum levels (maternal PAPP-A < 0.5) were associated with small for gestational age neonates. A significant positive correlation was also evident between maternal PAPP-A and babies’ growth parameters at 6 months of age. Our results suggest that maternal levels of PAPP-A in early pregnancy affect growth during both foetal and early postnatal life.

Human ciliopathies are hereditary conditions caused by defects of proteins expressed at the primary cilium. Among ciliopathies, Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS) and nephronophthisis (NPH) present clinical and genetic overlap, being allelic at several loci. One of the most interesting gene is TMEM67, encoding the transmembrane protein meckelin. We performed mutation analysis of TMEM67 in 341 probands, including 265 JSRD representative of all clinical subgroups and 76 MKS fetuses. We identified 33 distinct mutations, of which 20 were novel, in 8/10 (80%) JS with liver involvement (COACH phenotype) and 12/76 (16%) MKS fetuses. No mutations were found in other JSRD subtypes, confirming the strong association between TMEM67 mutations and liver involvement. Literature review of all published TMEM67 mutated cases was performed to delineate genotype-phenotype correlates. In particular, comparison of the types of mutations and their distribution along the gene in lethal versus non lethal phenotypes showed in MKS patients a significant enrichment of missense mutations falling in TMEM67 exons 8 to 15, especially when in combination with a truncating mutation. These exons encode for a region of unknown function in the extracellular domain of meckelin.

The unique ability of grain boundaries to act as effective sinks for radiation damage plays a significant role in nanocrystalline materials due to their large interfacial area per unit volume. Leveraging this mechanism in the design of tungsten as a plasma-facing material provides a potential pathway for enhancing its radiation tolerance under fusion-relevant conditions. In this study, we explore the impact of defect microstructures on the mechanical behavior of helium ion implanted nanocrystalline tungsten through nanoindentation. Softening was apparent across all implantation temperatures and attributed to bubble/cavity loaded grain boundaries suppressing the activation barrier for the onset of plasticity via grain boundary mediated dislocation nucleation. An increase in fluence placed cavity induced grain boundary softening in competition with hardening from intragranular defect loop damage, thus signaling a new transition in the mechanical behavior of helium implanted nanocrystalline tungsten.

Presence describes the feeling of reality and immersion that users of virtual/Internet environments have. Importantly, it has been suggested that there are individual and contextual differences regarding susceptibility to presence. These aspects of presence have been linked to both beneficial and disadvantageous uses of the Internet, such as online therapeutic applications and addictive Internet behaviours. In the present study, presence was studied in relation to individual anxiety symptoms and classroom-level openness to experience (OTE) using a normative sample of 648 adolescents aged between 16 and 18 years. Presence was assessed with the Presence II questionnaire, anxiety symptoms with the relevant subscales of the SCL-90-R, and OTE with the Five-Factor Questionnaire. A three-level hierarchical linear model was calculated. Results showed that experiencing presence in virtual environments dropped between the ages of 16 and 18 years. Additionally, although anxiety symptoms were associated with higher presence at 16 years, this association decreased with age. Results also demonstrated that adolescents in classrooms higher on OTE reported reduced level of experiencing presence. The practical and theoretical implications of these findings are discussed. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Rosa T Scaramuzzo,1,2 Massimiliano Ciantelli,1 Ilaria Baldoli,3 Lisa Bellanti,3 Marzia Gentile,1 Francesca Cecchi,3 Emilio Sigali,1 Selene Tognarelli,3 Paolo Ghirri,1–4 Stefano Mazzoleni,3 Arianna Menciassi,3 Armando Cuttano,1 Antonio Boldrini,1–4 Cecilia Laschi,3 Paolo Dario3 1Centro di Formazione e Simulazione Neonatale "NINA," UO Neonatologia, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; 2Istituto di Scienze della Vita, 3The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy; 4Università di Pisa, Pisa, Italy Abstract: Respiratory function is mandatory for extrauterine life, but is sometimes impaired in newborns due to prematurity, congenital malformations, or acquired pathologies. Mechanical ventilation is standard care, but long-term complications, such as bronchopulmonary dysplasia, are still largely reported. Therefore, continuous medical education is mandatory to correctly manage devices for assistance. Commercially available breathing function simulators are rarely suitable for the anatomical and physiological realities. The aim of this study is to develop a high-fidelity mechatronic simulator of neonatal airways and lungs for staff training and mechanical ventilator testing. The project is divided into three different phases: (1) a review study on respiratory physiology and pathophysiology and on already available single and multi-compartment models; (2) the prototyping phase; and (3) the on-field system validation. Keywords: simulation, lung, newborn, continuous medical education, respiratory system

Shifts in plant-community composition following habitat degradation and species invasions can alter ecosystem structure and performance of ecosystem services. In temperate North American woodlands, invasion by aggressive Eurasian shrubs has produced dense thickets with depauperate understory vegetation and increased rates of litter decomposition and nutrient cycling, attributes that could impair storage of carbon as soil organic matter (SOM). It is important to know if such impairment has occurred and, if so, the extent to which restoration can return this service. We used an oak-woodland restoration chronosequence in northeastern Illinois to contrast structural and functional attributes of unrestored areas dominated by Rhamnus cathartica (common buckthorn) with areas that had undergone buckthorn removal and ongoing, active management for less than 1 to 14 years. With increasing age, restored areas had higher understory plant diversity and cover (p < 0.0001 and 0.005, respectively) and higher litter mass (p = 0.018). These structural differences were associated with some evidence of reduced soil erosion (p = 0.027–0.135) but greater soil CO2 efflux (p = 0.020–0.033). Total particulate organic matter (POM) in the soil increased with restoration age, which was driven by increases in the slow-turnover, mineral-associated SOM fraction. However, variance was high and relationships were only weakly significant (p = 0.082 and 0.083 for total POM and mineral-associated SOM, respectively). Our results suggest that, in addition to better documented biodiversity benefits, beneficial changes to ecosystem properties and processes may also occur with active, long-term restoration of degraded woodlands.

A total of 58 patients consecutively underwent surgical treatment for lumbar intervertebral foraminal stenosis. We performed a microsurgical combined transarticular lateral and medial procedure with partial facetectomy in all patients to decompress the affected nerve root. All patients underwent assessment of depressive symptoms by means of the Zung Self Depression Scale (SDS). Subjective pain was self-evaluated by the Visual Analogue Scale (VAS). Both the tools were administered preoperatively, at 3 and 12 months' follow-up 0. The difference between the three SDS scores was significant (Friedman ANOVA, χ2 = 53.171, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative SDS scores as compared with three months follow-up (Z = -6.393, p < 0.0001) and the last, in turn, as compared with twelve months follow- up (Z = -3.720, p = 0.0002). The comparison between preoperative and 12 months' follow-up also reached significance (Z = -3.285, p = 0.001). About VAS, the difference between the three VAS scores was significant (Friedman ANOVA, χ2 = 69.932, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative VAS scores as compared with 3 months' follow-up (Z = -6.567, p < 0.0001) and the last, in turn, as compared with 12 months' follow-up (Z = -3.153, p < 0.002). The comparison between preoperative and 12 months' follow-up was also significance (Z = -5.520, p < 0.0001). Our results would alert clinicians to accurately consider the real need to treat and to include a careful psychiatric and psychological evaluation of these patients in the diagnosis and follow-up 0.

Background The Risk Management in healthcare is the set of complex actions implemented to improve the quality of health care and ensure patient safety, based on learning from errors Our aim was to increase the sensitivity of detection of adverse events getting by different sources of information Methods It was retrieved reports of adverse events occurring in a private hospital (100 beds), from January …

Background The patient falls continue to be a major problem in hospital. Each year, somewhere between 700.000 and 1.000.000 people in the United States fall in the hospital. In Italy, 24,6% of adverse events registered by Ministry of Health is represented by accidental patients falls. The aim of our study was to individuated and quantified risk factors for hospital patients falls. Methods A …

This work presents the first results of a research project seeking to build a simulation model able to reproduce the differences of Italian students’ performance at regional level. A preliminary qualitative cause-and-effect model defines the main variable involved in the inter-generational skill formation processes, as well as their interplay with the job market context and the triggering of motivational forces for new skill acquisition. Such model was designed according to a system dynamics perspective, considered suitable for capturing the interrelatedness of key variables and for providing useful simulation tools to conduct and communicate future scenario analyses. Keywords: regional difference; educational achievement; system dynamics; PISA

Dynamically altering protein concentration is a central activity in synthetic biology. While many tools are available to modulate protein concentration by altering protein synthesis rate, methods for decreasing protein concentration by inactivation or degradation rate are just being realized. Altering protein synthesis rates can quickly increase the concentration of a protein but not decrease, as residual protein will remain for a while. Inducible, targeted protein degradation is an attractive option and some tools have been introduced for higher organisms and bacteria. Current bacterial tools rely on C-terminal fusions, so we have developed an N-terminal fusion (Ntag) strategy to increase the possible proteins that can be targeted. We demonstrate Ntag dependent degradation of mCherry and beta-galactosidase and reconfigure the Ntag system to perform dynamic, exogenously inducible degradation of a targeted protein and complement protein depletion by traditional synthesis repression. Model driven analysis that focused on rates, rather than concentrations, was critical to understanding and engineering the system. We expect this tool and our model to enable inducible protein degradation use particularly in metabolic engineering, biological study of essential proteins, and protein circuits.

Tick borne encephalitis virus infection usually shows a biphasic course. In the first stage of illness symptoms are similar to a flu-like syndrome, then after a defervescence period, fever may represent with neurological manifestations ranging from mild meningitis to severe encephalomyelitis. We report the clinical case of an adult man presented with an acute proximal hyposthenia, severe hyperckemia, clinical and laboratoristic evidence of acute tick borne virus infection. This virus has a favourite tropism for the anterior horn cells of the cervical spine segment. Polio-like syndrome, usually affecting the upper limbs, is the clinical phenotype of an infection of the cervical motoneurons. Usually myelitis is associated to severe encephalitis and a complete diagnosis may be difficult in comatose patients. Rarely, an isolated polio-like syndrome may be the sole neurological complication of tick-borne encephalitis.

Nonlinear optical spectroscopy is applied to two types of metamaterials: (i) variations of split-ring resonators fabricated as periodic two-dimensional arrays of gold on SiO2, and (ii) gratings of periodically spaced straight wires of gold on multiferroic hexagonal single crystals from the RMnO3 family. Optical second harmonic generation (SHG) on samples of type (i) is used to characterize the nonlinear response of metamaterials in dependence of the photon energy and the size, shape, and symmetry of the nanoscopic building blocks constituting the metamaterials. We find a complex dependence of the SHG spectra on the design parameters that requires an in-depth theoretical analysis. SHG is applied to samples of type (ii) to enhance the nonlinear optical performance of functional materials by writing a metamaterial acting as optical catalyst on top. We observe an enhancement of the SHG signal induced by the ferroelectric order of the RMnO3 crystals, yet with pronounced variations between samples. Measurements of both types, (i) and (ii), show that a comprehensive understanding of the nonlinear optical properties of metamaterials requires one to go beyond a macroscopic symmetry treatment. In fact, structural inhomogeneities on the level of the nanoscopic building blocks have a major impact.

We have implemented a Matlab code to compute Discrete Extremal Sets (of Fekete and Leja type) on convex or concave polygons, together with the corresponding interpolatory cubature formulas. The method works by QR and LU factorizations of rectangular Vandermonde matrices on Weakly Admissible Meshes (WAMs) of polygons, constructed by polygon quadrangulation.

The study aim was to determine retrospectively whether the parallel use of 2 media [buffered charcoal yeast extract (BCYE) and medium of Wadowsky and Yee (MWY)] to isolate Legionella spp. from water samples taken from hospital water supply systems increased the sensitivity of the culture method as compared with methods/protocols in which only seeding on a selective medium is used. We analyzed the results obtained from 931 positive water samples. In 484 of the 931 positive water samples, Legionella spp. was isolated in the presence of other microorganisms; in 83% (400/484), we used MWY to count suspected colonies, which gave a lower number of unreadable plates. In the 447 samples containing only Legionella spp., the highest frequency of positive samples (93%, 418/447) was obtained with BCYE, whereas seeding on MWY yielded 78% (348/447) (P0.001). Evaluation of the influence of the media on the Legionella spp. counts obtained by the 2 media showed that BCYE agar produced significantly higher counts than MWY (P0.001). The major conclusions that may be drawn from our data are as follows: 1) BCYE gives a high recovery rate of positive samples (93%) and a much greater yield of Legionella spp. than MWY; 2) BCYE was necessary for the detection of non-L. pneumophila spp. which grew poorly on selective media; 3) selective media [MWY or GVPC (glycine, vancomycin, polymyxin B, and cycloheximide)] were necessary for the recovery of Legionella spp. when the non-selective medium (BCYE) was difficult to interpret because of contaminating background flora. The use of different media is recommended for routine water tests in hospitals.

Colorectal cancer (CRC) represents a major cause of morbidity and mortality. Although it is widely accepted that CRC screening in average risk populations lowers CRC incidence and mortality, a disappointedly low adherence rate to both faecal occult blood testing and colonoscopy-based screening programs has been observed in Italy and in other European countries. Main reasons for the low acceptance of colonoscopy-based CRC screening has been ascribed to lack of recommendations given by general practitioners, fear of discomfort or complications, embarrassment, and avoidance of unpleasant preparation. New advances in endoscopic technology such as colon capsule and robotic colonoscopy might represent the ideal tool for CRC screening since they reduce or eliminate procedure-related pain and discomfort. Moreover, no disinfection between procedures is required. Motion of the new probes along the gastrointestinal tract is achieved either in passive modality by utilizing the gut peristalsis (colon capsule) or in active "intelligent" modality by means of computer-assisted propulsion (robotic colonoscopy). In this review, the preliminary clinical results obtained with the new devices are summarized. It is expected that the new instruments will be soon available in clinical practice with the hope of increasing adherence to CRC screening programs.

Aims: To compare the efficiency of the ScanVIT-Legionella™ test (Vermicon, Munich, Germany) vs a conventional culture method for the quantification of Legionella spp. in hospital water samples in daily hospital practice. Methods and Results: The detection of Legionella spp. takes place on a cultivated filter brought into contact with dye-marked gene probes. The results are analysed under fluorescence microscopy. Bacteria that light up green belong to the genus Legionella; those that light up both green and red belong to the species Legionella pneumophila. Our results showed that the ScanVIT test has a sensitivity of 90%; agreement between the two methods was 82%. In the 48 samples that tested positive with both methods, the Legionella concentration detected by the culture method was consistently higher. A statistically significant difference between the results obtained with the two test methods emerged at the Wilcoxon test (P

M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20) enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

The influences of pre-treatments on the composition of Al–Zn alloys, containing 0.6–1.9 at.%Zn, are investigated using scanning and transmission electron microscopies, glow discharge optical emission spectroscopy and ion beam analysis. Alkaline etching, anodic alkaline etching and electropolishing result in zinc enrichments, just beneath the oxide/hydroxide films on the alloy surfaces. The enriched alloy, about 4–5 nm thick, contains zinc in solid-solution with aluminium, up to about 18 at.%. The highest and lowest enrichments are produced by alkaline etching and electropolishing respectively. For a given pre-treatment, the enrichment increases with increase in zinc content of the bulk alloy.

Dobyns, William/0000-0002-7681-2844; VERLOES, Alain/0000-0003-4819-0264 WOS: 000273581000002 PubMed: 19574260 Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). Methods In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. Results 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Conclusions Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L. US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K23NS45832, K24HD46712, NCRR 5KL2RR025015, R01NS050375]; March of Dimes Endowment for Healthier BabiesMarch of Dimes; Ames Endowment Fund; Allan and Phyllis Treuer Endowed Chair This work was supported by the US National Institutes of Health (grants K23NS45832 to MAP, K24HD46712 to IAG, NCRR 5KL2RR025015 to DD, R01NS050375 to WBD), the March of Dimes Endowment for Healthier Babies (DD, MAP, and IAG), the Ames Endowment Fund at Seattle Children's Hospital (IAG), and the Allan and Phyllis Treuer Endowed Chair (PFC) at Seattle Children's Hospital.

Zinc is an important alloying element in the 7000 series aluminium alloys. It is also an element that may enrich near the alloy surface during treatments of aluminium alloys by processes such as electropolishing, alkaline anodic etching and alkaline etching. The enrichment may occur since the change in Gibbs free energy per equivalent for formation of ZnO is less negative than that for formation of Al 2 O 3 . The enriched alloying element is present in an alloy layer up to ~5 nm thick located immediately beneath the alloy/film interface. In the present study, the dependence of the enrichment of zinc on the grain orientation of the alloy is investigated for a solid solution Al-1.1at.%Zn alloy. The enrichment of the zinc is developed by alkaline etching of the alloy. The grain orientation is determined by electron backscattering diffraction, with enrichments quantified on selected grains by Rutherford backscattering spectroscopy and medium energy ion scattering. The morphologies of the surfaces of the etched grains are characterised by scanning electron microscopy and atomic force microscopy. The findings reveal that the zinc enrichment ranges from 1.7 x 10 15 atoms/cm 2 to 3.9 x 10 15 atoms/cm 2 , with the greatest enrichment occurring on a grain of (100) orientation, while differing surface topographical textures are developed on the various grains.

Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid involved in multiple physiological processes. Importantly, dysregulated S1P levels are associated with several pathologies, including cardiovascular and inflammatory diseases and cancer. This report describes the successful production and characterization of a murine monoclonal antibody, LT1002, directed against S1P, using novel immunization and screening methods applied to bioactive lipids. We also report the successful generation of LT1009, the humanized variant of LT1002, for potential clinical use. Both LT1002 and LT1009 have high affinity and specificity for S1P and do not cross-react with structurally related lipids. Using an in vitro bioassay, LT1002 and LT1009 were effective in blocking S1P-mediated release of the pro-angiogenic and prometastatic cytokine, interleukin-8, from human ovarian carcinoma cells, showing that both antibodies can out-compete S1P receptors in binding to S1P. In vivo anti-angiogenic activity of all antibody variants was demonstrated using the murine choroidal neovascularization model. Importantly, intravenous administration of the antibodies showed a marked effect on lymphocyte trafficking. The resulting lead candidate, LT1009, has been formulated for Phase 1 clinical trials in cancer and age-related macular degeneration. The anti-S1P antibody shows promise as a novel, first-in-class therapeutic acting as a "molecular sponge" to selectively deplete S1P from blood and other compartments where pathological S1P levels have been implicated in disease progression or in disorders where immune modulation may be beneficial.

Defibrotide is a polydisperse oligonucleotide with antiatherosclerotic, anti-inflammatory, anti-ischaemic, pro-fibrinolytic and antithrombotic actions without significant systemic anticoagulant effects. It has been used in the treatment of various cardiovascular disorders, and especially in endothelial complications of allogeneic stem-cell transplantation. We reviewed the published work for the mechanism of action and clinical use of defibrotide to consolidate data and to describe new applications of this drug. We reviewed the most relevant papers on defibrotide published from November 1982 to January 2008. (selected through PubMed), and used recent meeting abstracts as sources for this review. Reports have suggested that defibrotide has clinical efficacy for treatment and prophylaxis of hepatic sinusoidal obstruction syndrome occurring after stem-cell transplantation. Animal models have clearly shown the potential antineoplastic effect of this drug. Further clinical investigations are needed to clarify this new application.

Sphingosine-1-phosphate (S1P) is a pleiotropic lysolipid that has recently been implicated in the regulation of tissue fibrosis. However, the fibrogenic potential of S1P in the eye has not previously been investigated. In the current study, we evaluated cells from the anterior and posterior segments of the eye for the presence of S1P and their potential ability to produce and respond to S1P. In addition, we investigated the regulatory role of S1P as a mediator of proliferation, cellular transformation and pro-fibrotic protein expression in human retinal pigmented epithelial cells. Expression of S1P receptors and sphingosine kinases (the enzymes that produce S1P) was examined using RT-PCR, and intracellular localization of S1P was examined using immunoblotting, immunohistochemistry and ELISA in primary human retinal pigmented epithelial (RPE) cells, primary human conjunctival fibroblasts (ConF), and primary human corneal fibroblasts (CF). RPE cell proliferation was determined using an MTT-based cell proliferation assay, and RPE myofibroblast transformation, collagen type I production and profibrotic protein expression were assessed using immunofluorescence, ELISA and immunoblot. S1P(1-3, 5) receptors and sphingosine kinases 1 and 2 were expressed and intracellular pools of S1P were detected in RPE cells, ConF and CF. S1P stimulated RPE cell proliferation in a dose- and time-dependent manner. S1P induced myofibroblast transformation of RPE cells, as indicated by increased alpha-smooth muscle actin (alpha-SMA) expression and its incorporation into prominent stress fibers, and promoted collagen type I production. S1P stimulated the expression of plasminogen activator inhibitor-1 (PAI-1) and heat shock protein 47 (HSP47), two proteins that are linked to increased tissue fibrosis. Combined, these data demonstrate that RPE cells, ConF and CF from the human eye not only have the molecular ability to produce and respond to S1P, but also contain S1P. Furthermore, S1P promotes proliferation, myofibroblast transformation, collagen production and pro-fibrotic protein expression by human RPE cells. These data suggest that S1P is a previously unrecognized mediator of profibrotic cellular function and signaling in the eye.

CuZnSOD is produced in overdose in cells with trisomy 21. This has been considered to be a cause of increased oxidative stress. In the present work we have studied the catalase and glutathione peroxidase activity in fibroblasts from 6, and blood cells from 30, subjects affected by Down syndrome. In the fibroblasts, catalase and glutathione peroxidase activities did not differ significantly from control cells. In platelets, lymphocytes, polymorphs and erythrocytes, no significant increase of catalase activity was found while glutathione peroxidase activity appeared significantly increased in platelets, polymorphs and erythrocytes but not in lymphocytes. These data seem to indicate that the increase of CuZnSOD in trisomy 21 cells does not affect the production of catalase. An increase, instead, of glutathione peroxidase has been detected in all blood cells, except in lymphocytes; this is a sign of a greater need for protection against the risk of lipoperoxidation. The fact that the enhancement of glutathione peroxidase activity could be assessed only in some types of cells examined suggests that the observed increase in those cells is probably a result of an additive effect of the overproduction of CuZnSOD due to gene dosage and the ordinarily higher content of oxygen radicals and peroxides.