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Background Limited information is available about the species of ticks infesting the cat and the pathogens that they harbor. The aims of the present study were to identify the species of ticks removed from cats living in Sicily and Calabria (Italy) and to detect DNA of vector-borne pathogens in the same ticks. Findings Morphological identification of 132 adult ticks collected throughout the year from cats was carried out. Real-time PCRs for Hepatozoon felis , Piroplasmid, Ehrlichia/Anaplasma spp., Rickettsia spp., Bartonella spp., Mycoplasma spp. and Leishmania infantum were performed from each individual tick. Ticks belonging to Rhipicephalus ( R. sanguineus sensu lato, R. pusillus ) and Ixodes ( I. ricinus , I. ventalloi ) genera were identified. Ixodes ventalloi was the most frequently found tick species (47 %). The positivity rate to at least one pathogen was 14.4 % (19/132 ticks). Leishmania infantum , Rickettsia spp. ( R. monacensis and R. helvetica ), Bartonella spp. ( B. clarridgeiae ), Piroplasmid ( Babesia vogeli ), and Ehrlichia/Anaplasma spp. ( E. canis ) DNAs were amplified in 8.3, 5.3, 1.5, 0.75 and 0.75 % of ticks, respectively. Hepatozoon felis , Anaplasma spp. and hemotropic Mycoplasma spp. DNAs were not detected. Four (21.1 %) out of nineteen positive ticks were co-infected. Conclusions This study provides novel data about ticks infesting cats and the DNA of pathogens that they harbor. In Southern Italy, anti-tick prophylaxis should be implemented throughout the year in cats without neglecting winter time.

Background Leishmaniosis caused by Leishmania infantum is one of the most important vector-borne diseases affecting animals and humans worldwide. Dogs are considered main reservoirs of the zoonotic forms, though in the last years the role of cats as reservoirs has been increasingly investigated. Feline leishmaniosis (FeL) occurs in endemic areas and no specific preventive measures have been investigated so far. In this study the efficacy of a 10% imidacloprid/4.5% flumethrin polymer matrix collar, licensed for tick and flea prevention, has been assessed against FeL in a longitudinal study on 204 privately owned cats from the Aeolian islands (Sicily), an area highly endemic for the disease. From March to May 2015 [Study Day 0 (SD 0)], cats negative for FeL were collared (G1, n  = 104) or left untreated (G2, n  = 100). Diagnosis consisted of serology and qPCR on blood and conjunctival swabs, which were collected at baseline (SD 0) and at the end of the study (SD 360). Interim clinical examinations were performed on SD 210 (when collars were replaced in G1) and SD 270. Results Of the 159 cats which completed the study, 5 in G1 and 20 in G2 were positive for L. infantum infection, in at least one of the diagnostic tests leading to a yearly crude incidence of 6.3% and 25.0% in G1 and G2, respectively ( P  = 0.0026). This translates into an efficacy of the collar of 75.0% in preventing feline Leishmania infection. The collar was generally well tolerated with no systemic adverse reactions and few local skin reactions were observed in the application area in four out of 104 treated cats (3.8%). Conclusions The 10% imidacloprid/4.5% flumethrin collar significantly reduced the risk of L. infantum infection in cats. To our knowledge, this is the first study in which a preventative strategy against feline Leishmania infection is assessed under natural conditions. These findings close a gap in veterinary medicine, in that they confirm this collar as a tool in reducing the risk of Leishmania infection in cats. Such a preventative tool could contribute to the reduction of the risk of the disease in animal and in human populations when included in integrated leishmaniosis control programmes.

Here in the Adirondacks, children combine academics with an extraordinarily vigorous and creative lifestyle— that includes helping to grow their own organic food .

ObjectiveCancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy.DesignA collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance.ResultsHere we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying Kras and Pik3ca mutation. Requirement for the triple targeting is due to the presence of cancer-associated fibroblasts, which release cytokines able to confer CR-CSC resistance to PI3K/AKT inhibitors. In contrast, targeting of PI3K/AKT as monotherapy is sufficient to kill liver-disseminating CR-CSCs in a model of adjuvant therapy.ConclusionsWhile PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting.

Left atrial volume (LAV) and emptying fraction (LAEF) are phasic during cardiac cycle. Their relationships to left ventricular end diastolic pressure (LVEDP) have not been fully defined. Forty one patients undergoing clinically indicated left heart catheterization were recruited for same day cardiovascular magnetic resonance (CMR). LAV and LAEF were assessed in cine images using biplane area and length method. Three phasic LAV was assessed at LV end systole (LAVmax), LV end diastole (LAVmin) and late LV diastole prior to LA contraction (LAVac). LAEF was assessed as global LAEF (LAEFTotal), passive (LAEFPassive) and active LAEF (LAEFContractile). The relationships of phasic LAV and LAEF to LVEDP were assessed using Receiver operating characteristic comparing areas under the curves (AUC). The mean age of the patients was 59 years. A history of heart failure was present in 16 (39%) with NYHA functional class III or IV in 8 (20%) patients. Average LV ejection fraction was 49 ± 16% ranging from 10% to 74% and LVEDP by catheterization 14 ± 8 mmHg ranging from 4 mmHg to 32 mmHg. LAVmin had the strongest association with LVEDP elevation (>12 mmHg) (AUC 0.765, p = 0.002), as compared to LAVmax (AUC 0.677, p = 0.074) and LAVac (AUC 0.735, p = 0.008). Among three phasic LAEF assessed, LAEFTotal had the closest association with LVEDP elevation (AUC 0.780, p = 0.001), followed by LAEFContractile (AUC 0.698, p = 0.022) and LAEFPassive (AUC 0.656, p = 0.077). Increased LAVmin and decreased LAEFTotal have the best performance in identifying elevated LVEDP among three phasic LAV and LAEF analyzed. Future studies should further characterize LA phasic indices in clinical outcomes.

The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents.

Traditional electrochemical techniques, such as linear polarization resistance (Rp), and electrochemical impedance spectroscopy (EIS), cannot be applied to gilded bronzes, as it may not be possible to interpret the results obtained due to the bimetallic nature of the studied material. The measurement of the macrocouple current generated by the gold/bronze galvanic couple can be used as an indicator of degradation processes. Nevertheless, this measurement cannot be performed directly on the original artifacts due to the systematic presence of short-circuits between the two metals. In the present work the use of galvanic sensors is proposed as a possible solution for the monitoring of gilded bronze artefacts. The sensors have been designed to simulate real gilded bronze surfaces in terms of composition and stratigraphy and have proved to be a reliable diagnostic tool for the in situ monitoring of the rates of deterioration of gilded bronze surfaces and to test new conservation treatments. Their set-up and application is reported and their performances discussed.

Discriminating between cardiac and pulmonary dyspnea is essential for patients’ management. We investigated the feasibility and ability of forced oscillation techniques (FOT) in distinguishing between acute exacerbation of COPD (AECOPD), and acute decompensated heart failure (ADHF) in a clinical emergency setting. We enrolled 49 patients admitted to the emergency department (ED) for dyspnea and acute respiratory failure for AECOPD, or ADHF, and 11 healthy subjects. All patients were able to perform bedside FOT measurement. Patients with AECOPD showed a significantly higher inspiratory resistance at 5 Hz, Xrs5 (179% of predicted, interquartile range, IQR 94–224 vs. 100 IQR 67–149; p = 0.019), and a higher inspiratory reactance at 5 Hz (151%, IQR 74–231 vs. 57 IQR 49–99; p = 0.005) than patients with ADHF. Moreover, AECOPD showed higher heterogeneity of ventilation (respiratory system resistance difference at 5 and 19 Hz, Rrs5-19: 1.49 cmH2O/(L/s), IQR 1.03–2.16 vs. 0.44 IQR 0.22–0.76; p = 0.030), and a higher percentage of flow limited breaths compared to ADHF (10%, IQR 0–100 vs. 0 IQR 0–12; p = 0.030). FOT, which resulted in a suitable tool to be used in the ED setting, has the ability to identify distinct mechanical properties of the respiratory system in AECOPD and ADHF.

The aim of this case–control study was to evaluate maternal–fetal and neonatal clinical outcomes in a group of patients with gestational diabetes mellitus (GDM) and pregestational diabetes such as diabetes mellitus type 1 (DM1) and diabetes mellitus type 2 (DM2) and compare them with those of patients without diabetes. A total of 414 pregnant women, nulliparous and multiparous, with single pregnancy were recruited. The selected patients were divided into two groups. Among 207 patients (group cases), 183 had GDM and 24 pregestational diabetes (of which n = 17 diagnosed with DM1 and n = 7 with diagnosis of DM2). Two-hundred-seven patients with a negative pathologic history of GDM, DM1 and DM2 represented the population of controls (group control). We reported an incidence of preterm delivery of 23.2% in the group of cases, of 18.3% in the group of patients with GDM and 66.7% in the group of patients DM1/2. Fetal growth disorders, such as intrauterine growth retardation (IUGR), small for gestational age (SGA), fetal macrosomia, were detected in four fetuses out of 207 (1.93%) in the control group and 20 fetuses out of 207 in the case group (9.67%, p-value 0.001); of these 16 of 183 fetuses of the GDM group (8.74%, p-value 0.002) and 4 of 24 fetuses of the DM1/2 group (16.67%, p-value 0.005). A very strong correlation between diabetes mellitus type 1 and preeclampsia (p-value < 0.0001) was observed. Close monitoring of pregnant women with diabetes is recommended to prevent maternal–fetal and neonatal complications.