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Purpose: We sought to establish whether nucleated red blood cells (NRBCs) are predictive of disposition, morbidity, and mortality for pediatric patients presenting to the emergency department (ED).Methods: A single center retrospective cohort study examining all ED encounters from patientsResults: The prevalence of NRBCs was 8.9% (4,195/46,991 patient encounters). Patient with NRBCs were younger (median age 4.58 vs 8.23 years; PConclusions: Presence of NRBCs is an independent predictor for mortality, including in-hospital mortality, ICU admission, CPR, and readmission within 30 days for children presenting to the ED.

OBJECTIVE: To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. STUDY DESIGN: We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. RESULTS: Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21–1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age

Pellet injection represents, to date, the most promising option for core fuelling of the EU-DEMO tokamak. Simulations with the HPI2 pellet ablation/deposition code indicate, however, that sufficiently deep fuel deposition requires injection from the High Field Side (HFS) at velocities ≳1 km/s. Two complementary inboard injection schemes are being explored: one makes use of guide tubes with curvature radii ≥6 m in the attempt of preserving pellet integrity at speeds of ˜1 km/s, the other is investigating the feasibility of injecting high-speed (˜3 km/s) pellets along “direct line of sight” (DLS) trajectories, from either the HFS or a vertical port. Options using quasi-vertical DLS paths routed across the upper vertical port have been explored first, as they can be more easily integrated, Unfortunately, the radial position of the available vertical access (≳9 m from the machine axis) turns out to be unfavorable; further simulations with the HPI2 code predict indeed that vertical injection may be effective only if pellets trajectories are well inboard the magnetic axis. High-speed injection through oblique inboard “DLS” paths, not interfering with the Central Solenoid (CS), are instead predicted to yield good performance, provided that the injection location is ≲2.5 m from the equatorial mid-plane. The angular spread of high-speed free-flight pellets, recently measured using an existing facility, turns out to be enclosed within ˜ 0.7°. This scatter cone may require significant cut off volume of the Breeding Blanket (BB). Moreover, DLS in-vessel conical penetrations may increase the neutron flux outside of the bio-shield, and also result in a significant heat load in the cryogenic pellet source. These issues are being investigated, to identify suitable shielding strategies; preliminary results are reported. The suitability of straight guide tubes to reduce the scatter cone, and hence the corresponding open cross section on BB penetration and the neutron streaming, will be explored as a further step. © 2019 Elsevier B.V.

Feline calicivirus (FCV) is a contagious viral pathogen that usually causes a mild, self-limiting respiratory disease. More recently, highly virulent FCV strains have emerged and have been associated with severe systemic infection, referred to as virulent systemic disease (VSD). The objective of this study is to report VSD cases in Italian cats along with the molecular characterization of two detected FCV strains. Three client-owned cats showed clinical signs resembling to those described for VSD cases. The cats were subjected to molecular investigations for detection of FCV and other feline pathogens. Histopathology and immunohistochemistry were performed on internal organs of one cat; molecular characterization of two detected FCV strains was obtained through sequence and phylogenetic analyses. Putative VS-FCV strains were detected in all three cats, which were co-infected with feline panleukopenia virus. The cat submitted to histopathology and immunohistochemistry displayed severe histological changes and FCV antigens in internal organs. Two Italian FCV strains, for which amplification of ORF2 was successful, were strictly related and formed a unique phylogenetic cluster. These viruses did not show consistent changes in the amino acid sequences with respect to reference VS-FCVs. The results of our study confirm that VS-FCV strains are circulating in Italy and that VSD diagnosis is complicated since both genetic and clinical markers have not been identified so far.

Multidrug resistance (MDR) is the leading cause of treatment failure in triple-negative breast cancer (TNBC) patients treated with doxorubicin (DXR). We aimed to investigate the potential of the antidiarrheal drug Loperamide (LPR) in sensitizing TNBC cells to DXR and elucidate the underlying molecular mechanisms. Therefore, we examined the effects of DXR alone or in combination with LPR on MDA-MD-231 cells viability using MTT assay, cell cycle, and apoptosis by flow cytometry, and the expression of the MDR-related genes (MDR1 and JNK1) and cell cycle/survival genes (p21, mTOR, and Bcl-2) by quantitative reverse transcription polymerase chain reaction. Results showed that adding LPR to DXR potentiated its antiproliferation effect and reduced its IC50 by twofolds compared with DXR alone. The value of the combination index of LPR/DXR was

The present work aimed to investigate the effects of nucleotide oral administration on oxidative stress biomarkers, immune responses, gut morphology, serum biochemical parameters, and growth performance in calves from birth to 25 d of life. A total of 40 male Holstein Friesian calves were randomly divided in 2 groups. All the calves were born and reared on the same commercial dairy farm. They were fed the same colostrum, milk replacer, and calf starter. Five grams/head of an additive were orally administered with a syringe directly in the mouth to calves of the nucleotide group (NG). The additive contained 74.12 g/100 g of nucleic acids from hydrolyzed yeast, and 75.38% was free nucleotide sodium salt. The other group represented the negative control (CG). At 25 d of life all of the calves were slaughtered. Calves supplemented with nucleotides had a higher final live weight and improved average daily gain, which was associated with better efficiency of nutrient use. Oral nucleotide administration did not affect IgG absorption efficiency; however, NG calves showed greater duodenum villi length and higher crypt depth compared with CG. Oral nucleotide administration increased the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and the antioxidant capacity [ferric reducing antioxidant power and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) scavenging activity] both in plasma and in liver. An enhanced ability of cells to counter reactive oxygen species- and reactive nitrogen species-mediated damage was also observed in peripheral blood mononuclear cells from NG. The findings highlight the effectiveness of oral nucleotide administration, and potentially dietary supplementation of nucleotides, in boosting oxidative and immune status in newborn calves.

In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded. © 2021. The Author(s). Published by the American Astronomical Society..

SARS-CoV-2 emerged from animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here, we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation., SARS-CoV-2 can infect cats and dogs, but the extent to which pets are infected in households remains unclear. Here, Patterson et al. test 919 companion animals in northern Italy and find that some dogs and cats from COVID-19 positive households can test positive for COVID-19 neutralizing antibodies, with dogs significantly more likely to do so if they came from COVID-19 positive households.

BackgroundPatients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments.ObjectivesOur long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the first 3 pandemic waves.MethodsA large series of 3,918 ASD patients (815 M, 3103 F; mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1).ResultsA significantly increased prevalence of COVID-19 (8.37% vs 6.49%; pInterestingly, a significantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%; p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients’ older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%; p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%; p=0.000).ConclusionThe cumulative impact of COVID-19 on ASD patients after the first 3 pandemic waves revealed less severe than that observed during the first phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series.Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients’ population.Of note, a significantly increased COVID-19-related mortality was recorded in only SSc patients’ subgroup, possibly favored by pre-existing lung fibrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy.Besides SSc, the patients’ subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.References[1]Ferri C, et al. Ann Rheum Dis. 2020 Oct 14 doi: 10.1136/annrheumdis-2020-219113.[2]Ferri C et al. J Autoimmun. 2021 Dec;125:102744. doi: 10.1016/j.jaut.2021.102744.[3]Visentini M et al. Ann Rheum Dis. 2021 Nov 24. doi: 10.1136/annrheumdis-2021-221248Disclosure of InterestsNone declared

Background: Although survival of children with advanced heart disease (AHD) has been improving, long-term morbidity remains high, leading to chronic conditions. There is little data on the perspectives of fathers caring for chronically ill children. This study describes the experience and prognostic awareness of fathers of hospitalized children with AHD. Methods: Cross-sectional survey study of parents caring for children hospitalized with AHD (age 30 d - 19 yr) admitted for ≥ 7 d between 2/18-2/19. Inclusion criteria: single ventricle, pulmonary vein stenosis, pulmonary hypertension, length of stay >30 d, …

To characterize parent-reported symptom burden and effectiveness of symptom management in children hospitalized with advanced heart disease.Prospective survey study of 161 parents whose child was admitted to a single institution with advanced heart disease between March 2018 and February 2019 using the Survey about Caring for Children with Heart Disease.Of the 161 patients, 54% were under 2 years old with a diagnosis of single ventricle physiology (39%), pulmonary hypertension (12%), and other congenital heart disease (28%). Over one-half (56%) of parents reported that their child was experiencing a high degree ("a great deal"/"a lot") of symptoms. The most frequently reported symptoms were pain (68%), fatigue (63%), and breathing difficulties (60%). Of the symptoms that were treated, parents perceived successful treatment to be least likely for their child's sleep disturbance (24%), depression (29%), and fatigue (35%). Parents who reported their child's functional status as New York Heart Association class III/IV were more likely to report that their child was experiencing "a great deal" of symptoms, compared with those who reported class I/II (51% vs 19%, P .001). Parents who reported their child was experiencing a high degree of suffering from fatigue were also more likely to report a high symptom burden (P .001).Parents of children with advanced heart disease reported high symptom burden with a broad spectrum of symptoms. Parents reported fatigue and psychiatric symptoms frequently and rarely reported treatment as successful. Parents' view of their child's symptom burden was concordant with their perception of their child's functional status.

The injection of cryogenic pellets from the low field side (LFS) has long been in use for core fuelling of fusion devices, but injection from the high field side (HFS) has proved to provide a more effective core particle deposition, despite the severe limitations imposed to the pellet speed (≤300 m/s) by inboard accessibility. In the future, an alternative approach may be that of injecting high-speed pellets from the HFS, through suitable “free-flight” paths, eliminating curved transfer systems. Furthermore, the expected length of the plasma discharges will require steady-state repetitive systems. ORNL and ENEA have been collaborating on high-speed injectors since 1990; they successfully realized a high-speed repeating pellet injector (2.55 km/s at 1 Hz). Since then, good progress has been achieved on both fronts of steady-state extruders, and operation and reliability of two-stage guns. A comprehensive R&D program is therefore proposed to investigate how far speed limits and repetition rates of combined two-stage guns and steady-state extruders technologies can be extended. Simulations results are presented showing pellet penetration for several injection locations on a tokamak under construction such as JT60-SA, on the basis of one set of design plasma parameters.

In the modern knowledge society, technological entrepreneurship represents a potential engine for the socioeconomic development of regions and territories. Skilled human capital endowed with social attitudes and transversal skills, the open configuration of working environments, and the change attitude of individuals, organizations, and society today represent the complementary factors to the new technologies for the development of a modern entrepreneurial society. Moreover, there is a possibility of access to financial sources that public and private actors decide to reserve for supporting technology entrepreneurship. This constitutes the final element that closes the entire process. It thus allows transforming a smart and innovative idea into a successful company. In particular, it becomes crucial to provide a clear and valuable support to each phase of startup creation (e.g., ideation, validation, build, launch, growth, and maturity), with a specific focus on the financial sources that can be used to implement each phase. In such a perspective, this chapter provides an overview of the main instruments, processes, and actors that can support the development of an entrepreneurial idea and the growth of a startup during the different stages by describing exemplary cases and initiatives of 3Fs funds, public funding, business angels, crowdfunding, venture capital, initial public offerings, corporate venture capital, banks, incubators, and accelerators.

Progression free survival (PFS) and tumour response (TR) have been investigated as surrogate endpoints for overall survival (OS) in advanced colorectal cancer (aCRC), however their validity has been shown to be suboptimal. In recent years, meta-analytic methods allowing for use of multiple surrogate endpoints jointly have been proposed. The aim of this research was to assess if PFS and TR used jointly as surrogate endpoints to OS improve their predictive value. Data were obtained from a systematic review of randomised controlled trials investigating effectiveness of different pharmacological therapies in aCRC: systemic chemotherapies, anti-epidermal growth factor receptor therapies, anti-angiogenic agents, other multi-targeted antifolate treatments and intra-hepatic arterial chemotherapy. Multivariate meta-analysis was used to model the association patterns between treatment effects on the surrogate endpoints (PFS, TR) and the final outcome (OS). Analysis of 33 trials which reported treatment effects on all three outcomes showed reasonably strong association between treatment effects on PFS and OS. A weak surrogate relationship was noted between the treatment effects on TR and OS. Modelling the two surrogate endpoints, TR and PFS, jointly as predictors of OS gave no marked improvement in neither surrogacy patterns nor the precision of predicted treatment effect in the cross-validation procedure. When investigating subgroups of therapy, only small improvement in precision of predicted treatment effects on the final outcome in studies investigating anti-angiogenic therapy was noted. Overall, the simultaneous modelling of two surrogate endpoints did not lead to improvement in association between treatment effects on surrogate and final endpoints in aCRC.

Viruses similar to human hepatitis C virus (HCV) in the Hepacivirus genus have been identified in several animal hosts, including cattle. Since its first discovery in Germany, bovine hepacivirus (BovHepV) has been described in several countries globally. However, limited data are available on BovHepV epidemiology and genetic variability. The aim of this study was to investigate the prevalence and genetic diversity of BovHepV in Italy. Viral RNA was identified in 37 (0.15%) of 24,820 bovine sera, with titres ranging from 1.09 × 103 to 8.27 × 106 RNA copies/ml. Upon sequencing and phylogenetic analysis of the 5'UTR and NS3 genomic portions, the Italian BovHepV strains segregated into at least four distinct subtypes (A, B, C and F) that are also co-circulating globally.

Natural hot springs are a common occurrence in Malaysia. These natural hot springs occur when water seeps into the earth and is heated by magma and pressure causes the water to rise again as a heated pool or hot springs. Some locals believe that these natural hot springs have curative effects and can cure skin ailments such as rashes, pimples and fungi infections. Whether this is true or not remains to be scientifically proven, but these places have become a magnet for tourists and those seeking healing. Some of Malaysia’s natural hot springs have developed into modern tourists’ attractions with shops, rest houses, restaurants and changing rooms built nearby to accommodate visitors who are interested by this natural phenomenon and the best example is the Poring Hot Springs, in Ranau, Sabah. Consequently, the objective of this paper is to briefly highlight the potential of Lojing’s hot springs as nature tourism attraction for the state of Kelantan. This paper provides a broad insight into the demand for services and facilities, location and characteristics of Lojing’s geothermal and natural mineral water resources, the opportunities available to expand and establish new facilities and an indication of the success of Sabah’s developments with the potential to be replicated in Lojing. Based on the content analysis done using Leximancer, it is apparent that Lojing’s hot spring requires intervention in terms of strategies that aimed at increasing tourist satisfaction. It is suggested that the theme “leisure” to be concentrated as the pull factor for Lojing hot spring-based tourism.

Endocrine orbitopathy (EO) can have important consequences, such as exophthalmos and restrictive strabismus. A retrospective study was performed of 35 patients with EO who underwent orbital decompression surgery and restrictive strabismus correction. Two surgical techniques for orbital decompression were analyzed: fat decompression by Olivari technique and three-wall bony expansion with fat decompression. Strabismus surgery was performed using adjustable or non-adjustable sutures under topical anaesthesia. Patients were divided into two groups according to the type of intra-orbital decompression performed, and the postoperative values resulting from the different fat decompression techniques were recorded. The preoperative and postoperative mean degrees of exophthalmos were 22.3 and 19.9mm, respectively, for the fat decompression group, and 24.3 and 19.8mm, respectively, for the bony expansion with transpalpebral fat decompression (combined form) group. The difference in residual prism dioptres between adjustable and non-adjustable suture techniques in patients who had previously undergone combined decompression was statistically significant. The management of patients with EO requires a multidisciplinary approach based on the collaboration of maxillofacial surgeons, ophthalmologists, and orthoptists. These results will allow the development of a more adequate strategy for the surgical treatment of restrictive strabismus in EO patients.

A series of firing tests have been performed on a laboratory-scale hybrid rocket engine of 200 N class, fed with gaseous oxygen through a converging nozzle injector, to assess the mechanical feasibility and regression rate of a newly developed paraffin-based fuel. Such an injector configuration, by producing recirculation at the motor head hand, has been already demonstrated to influence the standard fuels regression rate, which yields an increase with the port diameter at given mass flux. In this study, paraffin-fuel regression rate dependence on the mass flux and grain port diameter in the form of a power function is determined to be similar to that established with polymeric fuels, despite the different mechanism of consumption that involves the fuel surface liquid-layer instability other than the vaporization typical of classical polymers. Comparison with some data in the literature is presented. Data retrieved from the testing campaign are compared with numerical results obtained by adopting a simple but efficient modeling strategy and a commercial solver. The numerical solution gives evidence of the recirculating flow at the injector exit, which is also responsible for the paraffin contamination observed in the motor prechamber. A good agreement is found with chamber pressure experimentally measured.

The four-barrel, two-stage gun Ignitor Pellet Injector (IPI) was developed in collaboration between ENEA and ORNL. The prototype injector is presently located at Oak Ridge (TN, USA), and is normally operated locally through a control and data acquisition system developed in LabVIEW. More recently, a remote-control system has been set up, based on RealVNC®, which allows to operate the IPI from a control room in Italy. Tools for data transfer and storage into ENEA ICT area have also been provided. A Staging, Storage and Sharing system, named E3S, developed using OwnCloud as architectural component, is used for file synchronization and sharing of the data acquired by the diagnostic systems. It provides a homogeneous platform able to store and share heterogeneous data produced by many data acquisition systems in large nuclear fusion experiments. This paper reports about the implementation of the IPI remote control, and presents the application of E3S to this specific case, allowing easy storage and sharing of experimental data onto a wide-area distributed file-system, as well as remote data access via web-services based on MDS+ tool, integrated with MySQL metadata. A performance analysis of the architectural components is also introduced.

A novel protoparvovirus species was identified in domestic cats. The virus was distantly related to the well-known feline (feline panleukopenia virus) and canine (canine parvovirus type 2) parvoviruses, sharing low nucleotide identities in the capsid protein 2 (less than 43%). The virus was genetically similar (100% at the nucleotide level) to a newly identified canine protoparvovirus, genetically related to human bufaviruses. The feline bufavirus appeared as a common element of the feline virome, especially in juvenile cats, with an overall prevalence of 9.2%. The virus was more common in respiratory samples (9.5%-12.2%) than in enteric samples of cats (2.2%). The role of bufaviruses in the etiology of feline respiratory disease complex, either as a primary or a secondary agents, should be defined.

Monokine induced by interferon (IFN)-γ (MIG) / chemokine (C-X-C motif) ligand 9 (CXCL)9 is involved in the pathogenesis of psoriatic arthritis (PsA). It was demonstrated that both blood plasma-derived dendritic cells (pDCs) and pDCs isolated from rheumatoid arthritis (RA) and PsA synovial fluid (SF), expressed CXC receptor (R) 3 and CXCR4, and that the chemotaxis of blood-derived pDCs is stimulated by MIG, (IFN)-γ-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T-cell α chemoattractant (I-TAC) )/CXCL11 and stromal cell-derived factor 1 (SDF-1)/ CXCL12, present in RA and PsA SF. In PsA patients have been found a Th1 immune predominance at early stage of disease, while a reduction of these chemokines has been observed in long lasting PsA, with a significant increase of monocyte chemoattractant protein-1/IP-10 ratio. This suggest a shift from Th1 to the Th2 immune response in long lasting PsA. High levels of MIG has been found in patients with PsA and autoimmune thyroiditis too. This chemokine has been proposed as a useful marker to monitor the activity as well the progression of PsA. Efforts have been made to modulate or prevent the production of MIG in PsA aiming to alter the course of the disease.

The importance of the Type-1 helper immune response in the development of Vitiligo (Vit), and of chemokine receptor (CXCR)3 receptor and its chemokine monokine induced by interferon (IFN)-γ(MIG) has been shown by several studies. MIG/ interferon (IFN)-γ-inducible protein 10 (IP10) /CXCR3 axis mediated T-cell recruitment into the skin in Vit is an early event in the progression of the disease. MIG and IP10 circulating levels are increased in progressive Vit. It has been suggested that MIG and CXCR3 could be novel targets of future therapeutical approaches. Other studies have suggested that measuring MIG directly in the skin might be effective in clinical trials as an early marker of treatment response. Further studies are needed to explore the use of new molecules that act as antagonists of CXCR3, or block MIG, in Vit in a clinical setting.

The aim of this narrative review is to highlight the role of CXCL9 in Ulcerative Colitis (UC), in order to understand the mechanism underlying the inflammation in UC and to investigate also if Th1-chemokines could be useful as a marker of disease. It was shown that chemokine (C-X-C motif) receptor (CXCR)3 and its ligand chemokine, monokine induced by interferon (IFN)-γ(MIG)/ chemokine (C-X-C motif) ligand 9 (CXCL)9, are highly overexpressed both in the intestinal mucosa of mice with experimental colitis and in patients with UC (specifically, in lymphocytes, macrophages and epithelial cells). In epithelial colonic cells CXCL9 expression is increased by IFN-γ. MIG has an important role in the recruitment of mononuclear cells and granulocytes, so in maintaining the inflammation in UC. Since serum CXCL9 levels are related with UC disease activity, it could be a marker for the responsiveness of patients to treatments. It has been recently suggested that blocking CXCL9 may be a potentially effective therapy for moderately-to-severely active UC.

Background: Majority of studies investigating prognostic role of ER and PgR expression in ductal carcinoma in situ (DCIS) have failed to show a significant relationship with recurrence. Branched evolutionary tumour growth and resulting intratumour heterogeneity is now increasingly acknowledged in a variety of cancers. DCIS offers the opportunity to investigate relevance of clonal populations in different ducts that may have evolved differently and may impact outcome differently. We investigated prognostic role of ER and PgR expression in DCIS and impact of clonal variation in ER/PgR expression using material from UK/ANZ DCIS trial. Methods: Formalin-fixed paraffin embedded tissues (FFPETs) were collected from patients enrolled in the UK/ANZ DCIS trial, a randomised 2X2 factorial design trial investigating role of tamoxifen, radiotherapy or both as adjuvant treatment in DCIS. A nested case-control design was used; cases (patients with recurrence) were matched by treatment arm and age to 2 controls each (no recurrence). ER and PgR expression was evaluated on whole sections by immunohistochemistry using 1D5, PGR636 antibodies and EnVisionTM FLEX + detection system (Dako). Assays were scored by Allred method (positive if expression >1%) and clonal method. Clonal method documented presence of ducts with complete lack of ER or PgR expression in otherwise ER or PgR positive (Allred method) DCIS. Analyses categorising such multi-clonal DCIS as ER or PgR positive as per current practice (standard) and categorising these as ER or PgR negative DCIS (clonal method) were performed. Results: Of 540 samples (180 cases, 360 controls), ER and PgR status was evaluable in 504 and 498 patients respectively. ER expression was absent (ER-) in 148 (29.4%), 356 (70.6%) were ER positive (ER+) with 39 (7.7%) of these displaying multi-clonal expression (ERmulti-clonal). PgR expression was absent in 163 (32.7%), 335 (67.3%) were PgR positive with 84 (16.9%) of these displaying multi-clonal expression. ER- DCIS showed increased risk (Table) of in situ ipsilateral breast event (DCIS-IBE) and invasive ipsilateral breast event (I-IBE) (borderline significance). Prognostic discrimination was higher when ER status was determined by clonal method (ΔX2 1.57 for I-IBE and 9.05 for DCIS-IBE). Increases in the risk of I-IBE and DCIS-IBE were similar for ER- and ERmulti-clonal DCIS. TableEndpointComparisonScoring MethodHazard Ratio (95%CI)pI-IBEER- vs. ER+Standard1.75 (0.99-3.09)0.0544 ER- vs. ER+Clonal1.90 (1.10-3.30)0.0224 ER- vs. ER+*Clonal1.89 (1.05-3.41)0.0337 ERmulti-clonal vs. ER+*Clonal1.93 (0.74-5.03)0.1759DCIS-IBEER- vs. ER+Standard2.58 (1.68-3.94) Lack of PgR expression was only associated with increased risk of DCIS-IBE and PgR status did not add to the prognostic information provided by ER status. Conclusions: ER expression is prognostic for recurrence in DCIS. ER+ DCIS with distinct ER- clones has a recurrence risk similar to ER- DCIS. ER scoring should take clonality of expression into account. Citation Format: Thorat MA, Jones LJ, Levey PM, Elia G, Evagora CA, Bundred NJ, Fentiman IS, Forbes JF, Cuzick J. Prognostic role and impact of multi-clonal ER and PgR expression in ductal carcinoma in situ: Results from the UK/ANZ DCIS trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-01.

Riassunto Obiettivi Presentare un caso di ameloblastoma mandibolare trattato chirurgicamente con resezione settoriale a box e contemporaneo rinforzo con placca in titanio. Materiali e metodi Viene descritto un caso di recidiva di ameloblastoma mandibolare trattato presso il reparto di Chirurgia Cranio-Maxillo-Facciale dell’Azienda Ospedaliero-Universitaria Sant’Anna di Ferrara. L’intervento di asportazione radicale della neoformazione e rinforzo mandibolare con placca in titanio e stato programmato dopo accurato studio radiografico utilizzando la tecnica TC Dental Scan. Risultati e Conclusioni La chirurgia e il trattamento di scelta nell’ameloblastoma. Puo essere conservativa o radicale. Il primo approccio chirurgico e in genere conservativo, rispettando comunque il principio di radicalita in limiti ossei integri. L’ameloblastoma e un tumore odontogeno benigno, localmente invasivo e con un alto tasso di recidiva se non operato adeguatamente.

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta‐analysis is difficult because primary studies often use different methods of measurement and/or different cut‐points to dichotomise continuous factors into ‘high’ and ‘low’ groups; selective reporting is also common. We illustrate how multivariate random effects meta‐analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut‐points and/or methods of measurement. The models account for within‐study and between‐study correlations, which utilises more information and reduces the impact of unreported cut‐points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut‐point to reduce the number of unknown parameters. The models provide important inferential results for each cut‐point and method of measurement, including the summary prognostic effect, the between‐study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta‐analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut‐points than previously thought. In the second, a multivariate meta‐analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut‐points). © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

The indwelling urinary catheter (UC) is a significant bother for men after radical prostatectomy (RP) and should be removed as soon as possible without jeopardizing the outcome. Our aim was to assess the feasibility and safety of its removal on postoperative day (POD) 2 after robot-assisted laparoscopic RP (RALP). A consecutive series of patients undergoing RALP for localized prostate cancer (PCa) were prospectively enrolled. Inclusion criteria were: no bladder-neck reconstruction, watertight urethrovesical anastomosis at 150 ml filling, ≤ 200 ml of intraoperative bleeding, ≤ 80 ml of fluid from the drain on POD 1, clear urine from the UC on POD 2. Patients were discharged on POD 2. Continence was assessed at catheter removal and 1, 3 and 6 months after surgery. Urethrovesical anastomosis was performed with a standard technique on 3 layers. Sixty-six patients were enrolled. The UC was removed on POD 2 in all the cases and 96.4% of the patients were discharged on POD 2. Re-catheterization was needed 16 times and it was always performed easily. Twenty-four complications were reported by 20 patients, mostly Clavien–Dindo (CD) grade II; 2 CD IIIB complications were observed. No anastomotic strictures were diagnosed. At catheter removal, 29% of the patients were completely continent, 41% at 1 month, 67% at 3 months and 92% at 6 months. In selected patients, removing the UC 48 h after RALP is feasible and safe and has no negative impact on continence if compared with the best international standards.

Intra-vitam diagnosis of feline infectious peritonitis (FIP) is a challenge for veterinary diagnosticians, since there are no highly specific and sensitive assays currently available. With the aim to contribute to fill this diagnostic gap, a total of 61 effusions from cats with suspected effusive FIP were collected intra-vitam for detection of feline coronavirus (FCoV) antibodies and RNA by means of indirect immunofluorescence (IIF) assay and real-time RT-PCR (qRT-PCR), respectively. In 5 effusions there was no evidence for either FCoV RNA or antibodies, 51 and 52 specimens tested positive by IIF and qRT-PCR, respectively, although antibody titres ≥ 1:1600, which are considered highly suggestive of FIP, were detected only in 37 effusions. Three samples with high antibody levels tested negative by qRT-PCR, whereas 18 qRT-PCR positive effusions contained no or low-titre antibodies. qRT-PCR positive samples with low antibody titres mostly contained low FCoV RNA loads, although the highest antibody titres were detected in effusions with CT values > 30. In conclusion, combining the two methods, i.e., antibody and RNA detection would help improving the intra-vitam diagnosis of effusive FIP., Highlights • Effusions from cats with suspected FIP were analysed for detection of feline coronavirus (FCoV) antibodies and RNA. • Using a cut-off of 1:1600 for FCoV antibodies, only 40/61 samples were in agreement between the two tests. • Most effusions with low FCoV loads were found to contain low specific antibody titres. • Combining serological and molecular methods results in an increase of the diagnostic efficiency.

Lyme disease is an infectious disease caused by bacteria of the Borrelia type, that affects about 300,000 people a year in the USA and 65,000 people a year in Europe. Borrelia infection, and Lyme disease, following occupational exposure has been frequently reported in USA, Europe and Asia. The manifestations of Lyme disease include erythema migrans (EM), arthritis, neuroborrelliosis (NB), and others. Cytokines and chemokines primarily orchestrate leukocyte recruitment to the areas of Borrelia infection, and they are critical mediators of immune and inflammatory responses, in particular of the induction of interferon (IFN)-γ and IFN-γ dependent chemokines. In EM high levels of T helper (Th) 1 cells chemoattranctants [monokine induced by IFN-γ (MIG), IFN-γ-induced protein 10 (IP- 10), and IFN-inducible T cell alpha chemoattractant (I-TAC)] have been shown. Synovial tissues and fluids of patients with Lyme Arthritis (LA) (overall with antibiotic-refractory LA) contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly MIG and IFN-γ. In NB concentrations of IP-10 and I-TAC in the cerebrospinal fluid (CSF) were significantly higher, suggesting that IP-10 and I-TAC create a chemokine gradient between the CSF and serum and recruite C-X-C chemokine receptor 3-expressing memory CD4+ T-cells into the CSF of these patients. A positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction has also been shown. These results suggest that IFN-γ dependent chemokines are important biomarkers to monitor the progression and diffusion of the disease in patients with Borrelia infection; further larger studies are needed.

Equine hepacivirus is the closest homologue of hepatitis C virus. Limited data on the clinical features of this infection are available. We report the identification of a horse with high-titre viremia by equine hepacivirus. Over a 15-month follow-up, the clinical signs and the viremic status persisted, suggesting a chronic evolution.

Introduction The aim of this study was to determine the prognostic value of the first urinary albumin/creatinine ratio (ACR) for adverse maternal and neonatal outcomes and how it relates to other prognostic factors. Material and methods We performed a retrospective cohort study from December 2009 to February 2012 with analysis of demographic, clinical and biochemical data from two obstetric day assessment units in hospitals in Southeast Scotland. We included 717 pregnant women, with singleton pregnancies after 20 weeks’ gestation, referred for evaluation of suspected preeclampsia and having their first ACR performed. The ability of ACR to predict future outcomes was assessed in both univariable and multivariable logistic regression models. The latter assessed its prognostic value independent of (adjusting for) existing prognostic factors. Primary outcome measures were maternal and neonatal composite adverse outcomes, and a secondary outcome was gestation at delivery. Results In all, 204 women (28.5%) experienced a composite adverse maternal outcome and 146 women (20.4%) experienced a composite adverse neonatal outcome. Multivariate analysis of log-transformed ACR demonstrated that a 1-unit increase in log ACR is associated with an increased odds of adverse maternal [odds ratio 1.60, 95% confidence interval (CI) 1.45–1.80] and adverse neonatal (odds ratio 1.15, 95% CI 1.02–1.29) composite outcomes, and with reduced gestational age at delivery (coefficient: −0.46, 95% CI −0.54 to −0.38). Conclusions ACR is an independent prognostic factor for maternal and neonatal adverse outcomes in suspected preeclampsia. ACR may be useful to inform risk predictions within a prognostic model.

Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3). IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. IFN- γ-induced chemokines, as MIG and IP-10, may promote lymphocyte recruitment to HCC playing important roles in cancer immunology. The production of CXC chemokines by HCC cell lines has been shown. It has been identified immune-gene signature that predicts patient survival including the chemokine gene IP-10. Inflammatory cytokines (tumour necrosis factor-α, IFN-γ) and Toll-like receptor 3 ligands stimulate intratumoral production of these chemokines which drive T and Natural Killer cells tumor infiltration, leading to enhanced cancer cell death. Furthermore selective recruitment of CXCR3(+) B-cells that bridges proinflammatory IL-17 response and protumorigenic macrophage polarization in HCC has been shown, suggesting that blocking CXCR3(+) B-cell migration or function may help defeat HCC. It has been also shown that the overexpression of IP-10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential adjuvant therapy to sensitize HCC-cisplatin treatment.