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The presented research aims to define a parametric modelling methodology that allows, in short time and at a sustainable cost, the digital acquisition, modelling and semantic structuring of urban city blocks to facilitate 3D city modelling applied to historic centres. The methodology is based on field surveying and derives 3D data for the realisation of a parametric City Information Model (CIM). This is pursued through the adoption of parametric modelling as main method combined with AI procedures like supervised machine learning. In particular, the Visual Programming Language (VPL) Grasshopper is adopted as main working environment. The methodology proposed, called Scan-to-CIM, is developed to automate the cognitive operations of interpretation and input of surveying data performed in the field in order to create LoD4 city block models in a semi-automatic way. The proposed Scan-to-CIM methodology is applied to a city block located in the historic centre of Catania, Italy. [ABSTRACT FROM AUTHOR]

Abstract Background Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug. Results We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105-254), we identified the 149-166 region as the adiponectin active site. Three-dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 μM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1. In vivo, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice. Conclusions ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies.

Heavy metals and metalloids in the environment are recognised as a threat to the health of organism. Terrestrial birds are ideal subjects for the examination of these pollutants because of their high mobility and high intra- and interspecific variation in trophic levels. We examined the contents of 6 trace metals (Cd, Pb, Cr, Sb and V) and metalloids (As) in the liver, kidney, muscle, and feathers of woodcocks (Scolopax rusticola) from Southern Italy by a validated ICP-MS method. Significant differences in trace elements were found in all the tissues examined (p < 0.05). The highest Sb and Cr levels were found in feathers samples with mean values of 0.019 mg/Kg and 0.085 mg/Kg, respectively. High Pb levels were found in muscle, with 23 % of the samples exceeding the limits set by the European Union. Cd was predominantly found in the kidney samples (0.76 mg/Kg). Vanadium was the less abundant trace metal, showing the highest concentrations in the liver (0.028 ± 0.011 mg/Kg). Higher As levels were found in muscle (0.02 ± 0.015 mg/Kg). No significant differences between sex and age classes (juveniles vs. adults) were found, nor were there correlations between morphometric parameters and trace metal/metalloid contents. Principal Component Analysis determined differences in metal accumulation between tissues. Feathers were confirmed as useful indicators of metal contamination. The results of this work confirmed that the accumulation of toxic elements in the tissues of woodcocks is primarily influenced by ecological traits such as feeding habits and migration status. Statistical analysis of the tissues would seem to exclude important accumulation phenomena of Pb. The high levels found in the muscle could be due to lead ammunition. This work provides the first data on the accumulation of As, Cr, Sb, and V in woodcocks tissue, providing a more comprehensive insight into the potential impact of these pollutants on birds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Maintaining tissue function while eliminating infected cells is fundamental to host defense. Innate inflammatory damage contributes to lethal influenza and COVID-19, yet other than steroids, immunomodulatory drugs have modest effects. Among more than 50 immunomodulatory regimes tested in mouse lethal influenza infection, only the previously reported early depletion of neutrophils showed efficacy, suggesting that the infected host passes an early tipping point in which limiting innate immune damage alone cannot rescue physiological function. To re-balance the system late in infection, we investigated whether partial limitation of viral spread using oseltamivir (Tamiflu) together with enhancement of epithelial repair by blockade of interferon signaling or the limitation of further epithelial cell loss mediated by cytotoxic CD8 + T cells would prevent death. These treatments salvaged a large fraction of infected animals, providing new insight into the importance of repair processes and the timing of adaptive immune responses in survival of pulmonary infections.

Modelling approaches play a crucial role in supporting local public health agencies by estimating and forecasting vector abundance and seasonality. However, the reliability of these models is contingent on the availability of standardized, high-quality data. Addressing this need, our study focuses on collecting and harmonizing egg count observations of the mosquito Aedes albopictus, obtained through ovitraps in monitoring and surveillance efforts across Albania, France, Italy, and Switzerland from 2010 to 2022. We processed the raw observations to obtain a continuous time series of ovitraps observations allowing for an extensive geographical and temporal coverage of Ae. albopictus population dynamics. The resulting post-processed observations are stored in the open-access database VectAbundance.This initiative addresses the critical need for accessible, high-quality data, enhancing the reliability of modelling efforts and bolstering public health preparedness., (© 2024. The Author(s).)

The Eurasian woodcock ( Scolopax rusticola ) belongs to those bird species that make systematic migratory flights in spring and autumn in search of favorable breeding and wintering areas. These specimens arrive in the Mediterranean Area from northeastern European countries during the autumn season. The purpose of this study was to assess whether woodcocks can carry antibiotic resistance genes (ARGs) along their migratory routes. Although the role of migratory birds in the spread of some zoonotic diseases (of viral and bacterial etiology) has been elucidated, the role of these animals in the spread of antibiotic resistance has not yet been clarified. In this study, we analyzed the presence of beta-lactam antibiotic resistance genes. The study was conducted on 69 strains from 60 cloacal swabs belonging to an equal number of animals shot during the 2022-2023 hunting season in Sicily, Italy. An antibiogram was performed on all strains using the microdilution method (MIC) and beta-lactam resistance genes were investigated. The strains tested showed no phenotypic resistance to any of the 13 antibiotics tested; however, four isolates of Enterobacter cloacae and three of Klebsiella oxytoca were found to carry the bla IMP-70 , bla VIM-35 , bla NDM-5 and bla OXA-1 genes. Our results confirm the importance of monitoring antimicrobial resistance among migratory animals capable of long-distance bacteria spread.

Feline leishmaniosis is a worldwide infection caused by the parasite of the genus Leishmania transmitted by sandflies. Based on the complexity of epidemiology and diagnosis of this infection, the role of cats in the epidemiology and clinical impact of disease is still under debate. By using serological and molecular methods, this study aimed to update the epidemiology of the infection in different feline populations from various areas of Italy and to study factors associated with the infection. Of 1490 cats tested, 124 (8.3%, 95% CI 6.9-9.9) were infected, 96 had only specific L. infantum IgG, 18 were only positive for parasite DNA and 10 were both IFAT and qPCR positive. Risk factors for infection were sampling in the winter season (OR = 3.2, 95% CI 2.2-4.8), originating from the Sicily region (OR = 2.0, 95% CI 1.3-3.0), male gender (OR = 1.8, 95% CI 1.1-3.2), outdoor lifestyle (OR = 2.3, 95% CI 0.9-5.6) and seropositivity for FIV antibodies (OR = 2.2, 95% CI 1.2-4.2), while sampling in the spring (OR = 0.5, 95% CI 0.3-0.7) and summer (OR = 0.3, 95% CI 0.1-0.7), and originating from the Lazio region (OR = 0.1, 95% CI 0.05-0.4) were protective factors for infection. In endemic areas, Leishmania infection should be investigated by using both serological and molecular methods and cats should be protected from sandfly bites, particularly if they are FIV infected.

The in vitro cultivation of Leishmania and Trypanosoma parasites plays an important role in the diagnosis and treatment of parasitic diseases. Although Evans's modified Tobie and Novy-MacNeal-Nicolle media, for Leishmania spp. and Trypanosoma cruzi , respectively, are the two commonly used media for both isolation and maintenance of strains in vitro, their preparation is expensive and laborious and requires fresh rabbit blood from housed animals. The purpose of this study was to evaluate the in vitro growth of both parasites with an alternative monophasic, blood-free, easy, and affordable medium called RPMI-PY, which was previously demonstrated suitable for the in vitro growth of Leishmania infantum . The potential growth of different Leishmania species and Trypanosoma cruzi was evaluated in traditional culture media versus RPMI-PY medium, and we recorded the protozoa parasites' morphology via orange acridine-ethidium bromide staining. The results of our study show that RPMI-PY medium can be used for Trypanosoma cruzi , Leishmania amazonensis , Leishmania major , and Leishmania tropica species since in all the species except Leishmania braziliensis , the exponential growth of the parasite was observed, in many cases higher than conventional media. The staining confirmed not only their growth during the 72 h investigation but also the optimal morphology and viability of the protozoa in the RPMI-PY medium.

Leishmaniasis is an important vector-borne disease that represents a serious public health problem, including in Sicily (Italy), which is considered an endemic area. We collected canine, feline and human data from 2013 to 2021 in Sicily, while entomological surveys were conducted only in 2013 and 2021. Overall, 23,794/74,349 (34.4%) of dogs and 274/4774 (11.8%) of cats were positive in one or more diagnostic tests. A total of 467 cases of human Leishmaniasis were reported, with 71% showing cutaneous and 29% visceral involvement. The provinces with the largest number of patients were Agrigento (45.4%) and Palermo (37%). In 2013, Phlebotomus perfiliewi was the dominant sandfly species in Sicily (68.7%), followed by Phlebotomus perniciosus (17.2%) and Sergentomya minuta (14%). In 2021, Phlebotomus perfiliewi was confirmed as the most common species (61.6%), followed by Phlebotomus perniciosus (33.1%) and Sergentomya minuta (4.7%). Of particular interest was the identification of Phlebotomus papatasi (0.41%) in Agrigento. Our retrospective study can inform health authorities for the development of appropriate screening, treatment and control strategies to reduce Leishmania incidence rate. This study examined the present state of Leishmaniasis control, surveillance, and prevention in Sicily, but also highlighted deficiencies that could be addressed through the application of One-Health principles.

The response to allopurinol treatment and survival time of a case of feline leishmaniosis in a FIV co-infected cat is herein reported. In May 2019, a 13-year-old neutered European Shorthair male was referred due to weight loss and exfoliative dermatitis. Lymphadenomegaly and splenomegaly were detected upon clinical inspection, while the presence of several Leishmania infantum amastigotes were detected on splenic and lymphonodal fine needle aspiration (FNA). Allopurinol (10 mg/kg PO q 12 h) was administered. After two months, the cat's clinical symptoms disappeared, and the owners decided to interrupt the therapy. In February, two reddish nodular fleshy neoformations appeared in both eyes, and amastigotes of Leishmania were detected by cytology on conjunctival swabs. Allopurinol treatment was re-started at the same rate; the ocular lesions regressed in two weeks, and the owner again decided to interrupt the therapy. In July, the patient had a new relapse, but the owner, tired of continuous relapses, refused further treatment of the disease. The cat's health condition continued to worsen: in October 2021, the ocular lesions appeared again, and in November the patient died. This case underlines the effectiveness of allopurinol and highlights how interruption of treatment frequently leads to relapse, impairing the animal's health condition and prognosis.

The aim of this preliminary study was to investigate the presence of Mycoplasma agalactiae ( Ma ) or other Contagious Agalactia (CA) causative organisms, in hard ticks infesting milking sheep and goats in endemic areas for CA in Sicily (South-Italy). Although there is accumulating evidence to support the role of ticks in the transmission of blood-borne haemoplasmas, information regarding their role in the transmission of CA, remains scarce. Ticks ( n = 152) were collected from 25 lactating sheep and goats from three farms with previous outbreaks of CA. Microbiological and biomolecular, as well as serological analysis were performed on milk, tick, and serum samples, respectively. Rhipicephalus bursa species predominated, comprising 84.8% of the sampled ticks. Mycoplasma-like colonies were isolated from 5/56 (8.9%) tick pools and were identified as Ma by specific PCR and 16S rRNA gene sequencing. Unexpectedly, the organism was isolated from R. bursa ticks recovered only from animals whose milk tested negative for the pathogen. This preliminary demonstration suggests the potential role for ticks to act as a reservoir for the organisms, with potential involvement in the spread and maintenance of CA. Further work is required to determine the location of the organisms within the body of the ticks and to assess transmission potential.

Background: West Nile Disease (WND) is a zoonotic mosquito-borne infection involving viral pathogens, human and animal hosts, vectors and environment. Cooperation among medical, veterinary and entomological fields has been promoted by the Italian Public Health Authorities, and an integrated West Nile Virus (WNV) Surveillance Plan has been in force in Italy since 2016 to prevent the transmission risk of WND to humans through an early detection of viral circulation by animal and entomological surveillance. This managing model is unique in Europe., Objectives: This survey aimed at presenting the 'One Health' approach applied in 2016 to the first autochthonous human case of West Nile Neuroinvasive Disease (WNND) in Sicily (Southern Italy)., Methods: Serological (anti-WNV IgM and IgG ELISA, anti-WNV neutralizing antibodies) and molecular tests were conducted on blood, liquor and urine of a 38-year-old man with encephalitis and meningitis. Overall, 2704 adult culicides from 160 mosquito catches were morphologically identified. Female mosquitoes were analysed in pools for WNV RNA detection. Serological (anti-WNV IgM and IgG ELISA) and molecular analyses for WNV were carried out in 11 horses, 271 chickens and two dogs sampled in farms around the man's residence., Results and Conclusions: WNND was confirmed by serological analysis on patient's liquor and serum. Collected mosquito species included Culex pipiens (93.56%, CI 95% 92.64%-94.49%), Aedes albopictus (5.25%, CI 95% 4.41%-6.09%), Culex hortensis (0.59%, CI 95% 0.30%-0.88%), Culiseta longiareolata (0.55%, CI 95% 0.27%-0.83%) and Anopheles maculipennis s.l. (0.04%, CI 95% -0.04% to 0.11%). Mosquito pools were negative for WNV RNA. Two dogs (100%) and two horses (18.18%, CI 95% -4.61 to 40.97%) resulted positive for anti-WNV specific antibodies. The 'One Health' approach allowed to report the first human neuroinvasive WND in Sicily and to confirm the local circulation of WNV in animals of the same area where the clinical case occurred, defining the autochthonous origin of the infection., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The airways are constantly exposed to a multitude of inhaled particles and, as such, require a finely tuned discrimination between harmful or potentially threatening stimuli, and discrete responses to maintain homeostasis. Both the immune and nervous systems have the ability to sense environmental (and internal) signals, to integrate the obtained information and to initiate a protective reaction. Lung immunity and innervation are known to be individually involved in these processes, but it is becoming clear that they can also influence one another via a multitude of complex mechanisms. Here, we specifically describe how sensory innervation affects airways immunity with a focus on pathological conditions such as asthma or infections, describing cellular and molecular mechanisms, and highlighting potentially novel therapeutic targets., (Copyright © 2021. Published by Elsevier B.V.)

Camels represent an important resource for inhabitants of the most arid regions of the world and their survival is mainly related to environment conditions including the risk of parasitic diseases, which may represent a significant cause of losses in livestock production of these areas. Camels may be parasitized by several hematophagous arthropods, which can be vectors of several diseases including zoonosis. This study aimed to investigate in dromedary camels and their ticks the importance of tick-borne hemoparasites that might be responsible for a recent and obscure morbidity of camels in Al Dhafra region of Abu Dhabi, UAE. Blood samples and ticks from 93 naturally infected camels belonging to 36 herds, affected by variable acute clinical syndromes lasting from 3 to 5 days, were analyzed through molecular techniques for specific DNA presence of different blood pathogens: Anaplasma marginale / Anaplasma ovis , Anaplasma phagocytophilum , Coxiella burnetii, Babesia spp., and Theileria spp. DNA. All the 72 ticks collected belonged to the Hyalomma dromedarii species and were negative for blood pathogens. n = 15 camels (16.1%) were found positive to the following tick-borne hemoparasites: A. phagocytophilum 11 (11.8%), Coxiella burnetii 3 (3.2%), and Babesia/Theileria spp. 2 (2.1%). One singular camel showed coinfection of C. burnetii and A. phagocytophiulm . Genetic profile of C. burnetii showed a high phylogenetic relatedness to European, Asian and African C. burnetii strains. This is the first laboratory investigation on tick-borne pathogens in camels in UAE, and the first report of A. phagocytophilum and C. burnetii . Moreover, since the detected pathogens are recognized pathogens for humans, this study highlights the zoonotic risk for humans working in camel husbandry.

Tropical theileriosis is a tick-borne disease caused by hemoprotozoan parasites with considerable veterinary and economic impact worldwide. Ticks transmitting the disease belong to the Haemaphysalis , Rhipicephalus , and Hyalomma genera. The Hyalomma genus is very common in Sicily (Italy) and represents the main Theileria annulata vector in the island. Data concerning the molecular epidemiology of this pathogen are missing in the region. In 2018-2019, blood and serum samples were collected from 480 cows in seven Sicilian farms from four different provinces. Seroprevalence in the farms ranged from 22% to 71%. Three farms were selected for molecular analysis consisting of real-time PCR targeting the almost complete 18S ribosomal RNA (rRNA). Four amplicons per farm were sequenced and phylogenetic analyses were carried out. The four sequences were identical within each farm and showed 92-99% identity with the other farms and with sequences from Genbank. According to the phylogenetic analysis, these three sequences and an additional one from a laboratory-cultured Theileria annulata strain obtained in 1999 belonged to a single T. annulata clade with good bootstrap support with other sequences from Italy, India, and Iran, indicating limited geographical and temporal genetic variability of the parasite. This study represents the first phylogenetic analysis of T. annulata in Sicily, which will be useful to improve the strategies for theileriosis control and prevention.

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens.

Rickettsia species are an important cause of emerging infectious diseases in people and animals, and rickettsiosis is one of the oldest known vector-borne diseases. Laboratory diagnosis of Rickettsia is complex and time-consuming. This study was aimed at developing two quantitative real-time PCRs targeting ompB and ompA genes for the detection, respectively, of Rickettsia spp. and R. conorii DNA. Primers were designed following an analysis of Rickettsia gene sequences. The assays were optimized using SYBR Green and TaqMan methods and tested for sensitivity and specificity. This study allowed the development of powerful diagnostic methods, able to detect and quantify Rickettsia spp. DNA and differentiate R. conorii species.

Abstract: Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies, and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type-specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3 1/2 months after the initial injury. This raises the question of whether the commonly used categorisation of pain into "inflammatory" and "neuropathic" is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq data sets on neurons, macrophages, and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data mining of peripheral neuroimmune interactions. http://rna-seq-browser.herokuapp.com/., (Copyright © 2020 International Association for the Study of Pain.)

Increasing evidence suggests that nerve fibers responding to noxious stimuli (nociceptors) modulate immunity in a variety of tissues, including the skin. Yet, the role of nociceptors in regulating sterile cutaneous inflammation remains unexplored. To address this question, we have developed a detailed description of the sterile inflammation caused by overexposure to UVB irradiation (i.e., sunburn) in the mouse plantar skin. Using this model, we observed that chemical depletion of nociceptor terminals did not alter the early phase of the inflammatory response to UVB, but it caused a significant increase in the number of dendritic cells and αβ + T cells as well as enhanced extravasation during the later stages of inflammation. Finally, we showed that such regulation was driven by the nociceptive neuropeptide calcitonin gene-related peptide. In conclusion, we propose that nociceptors not only play a crucial role in inflammation through avoidance reflexes and behaviors, but can also regulate sterile cutaneous immunity in vivo., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Oral metronomic therapy (OMV) is particularly suitable for palliative care, and schedules adapted for unfit patients are advisable. This study investigated the effects of oral vinorelbine given every other day without interruption and its pharmacokinetic profile in patients with advanced lung cancer. Materials and Methods Ninety-two patients received OMV at doses of 20, 30 or 50 mg. Toxic events, clinical benefit and overall survival were analysed. Blood pharmacokinetics were evaluated in 82 patients. Results Median treatment duration and overall survival were 15 (range 1.3-144) and 32.3 weeks, respectively; fourty-eight (60%) patients experienced clinical benefit. Outcomes were unrelated to previous therapies, age, histology or comorbidities. Toxicity was associated with higher blood concentrations of the drug. Pharmacokinetics were stable for up to two years, and were not influenced by treatment line or age. Conclusions OMV produced non-negligible survival in patients and also showed stable long-term blood concentrations. The schedule of 20-30 mg every other day without interruption gave good tolerability and clinical benefit.

Trastuzumab is a key therapy for patients with human epidermal growth factor receptor 2 positive breast cancer (BC). However, it may cause left ventricular dysfunction, resulting in withdrawal of therapy. Left atrium (LA) enlargement has proven to cue subclinical ventricular dysfunction in various clinical setting. Aim of the study was to investigate the association between LA volume index (LAVI) change over time and the development of Cancer Therapeutics Related Cardiac Dysfunction (CTRCD). Consecutive human epidermal growth factor receptor 2 positive BC patients were retrospectively included. Transthoracic echocardiography was performed before starting Trastuzumab and at every 3 up to 12 months. LA volume was measured using the modified Simpson's rule and indexed for body surface area. Ninety patients formed the study population. All patients had a complete 12 months follow-up. Mean baseline LAVI was 27 ± 8 ml/m 2 and it was dilated (≥34 ml/m 2 ) in 10 patients (11%). During follow-up, CTRCD occurred in 19 (21%) patients and there was modest LAVI enlargement, with a mean increase of 3 ± 2 ml/m 2 (p = 0.0002 vs. baseline). LAVI dilation was significantly higher in patients with CTRCD (average increase at the time of CTRCD vs. baseline: 7 ± 6 ml/m 2 , p = 0.008), versus patients without CTRCD (average increase at 12 months of follow-up 2±1, p = 0.02), p for comparison = 0.004. LAVI dilatation over time predicted CTRCD independently from baseline LAVI values and the presence of systemic arterial hypertension (OR for 5 ml/m 2 dilation was 1.56 [95%CI 1.09 to 2.37], p = 0.01). Trastuzumab related CTRCD is associated with significant LAVI morphological remodeling in BC patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Insecticide resistance is an increasing problem worldwide that limits the efficacy of control methods against several pests of health interest. Among them, Aedes albopictus mosquitoes are efficient vectors of relevant pathogens causing animal and human diseases worldwide, including yellow fever, chikungunya, dengue, and Zika. Different mechanisms are associated in conferring resistance to chemical insecticides. One of the most widespread and analysed mechanisms is the knockdown resistance ( kdr ) causing resistance to DDT and pyrethroids. The mechanism is associated with mutations in the voltage sensitive sodium channel, which is involved in beginning and propagation of action potentials in nervous cells. The mechanism was originally discovered in the housefly and then it was found in a large number of arthropods. In 2011, a kdr associated mutation was evidenced for the first time in A. albopictus and afterward several evidences were reported in the different areas of the world, including China, USA, Brazil, India, and Mediterranean Countries. This review aims to update and summarize current evidences on kdr in A. albopictus , in order to stimulate further researches to analyse in depth A. albopictus resistance status across the world, especially in countries where the presence of this vector is still an emerging issue. Such information is currently needed given the well-known vector role of A. albopictus in the transmission of severe infectious diseases. Furthermore, the widespread use of chemical insecticides for control strategies against A. albopictus progressively lead to pressure selection inducing the rise of insecticide resistance-related mutations in the species. Such event is especially evident in some countries as China, often related to a history of uncontrolled use of chemical insecticides. Thus, a careful picture on the diffusion of kdr mutations worldwide represents a milestone for the implementation of control plans and the triggering of novel research on alternative strategies for mosquito-borne infections.

Down Syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and results in a spectrum of phenotypes including learning and memory deficits, and motor dysfunction. It has been hypothesized that an additional copy of a few Hsa21 dosage-sensitive genes causes these phenotypes, but this has been challenged by observations that aneuploidy can cause phenotypes by the mass action of large numbers of genes, with undetectable contributions from individual sequences. The motor abnormalities in DS are relatively understudied-the identity of causative dosage-sensitive genes and the mechanism underpinning the phenotypes are unknown. Using a panel of mouse strains with duplications of regions of mouse chromosomes orthologous to Hsa21 we show that increased dosage of small numbers of genes causes locomotor dysfunction and, moreover, that the Dyrk1a gene is required in three copies to cause the phenotype. Furthermore, we show for the first time a new DS phenotype: loss of motor neurons both in mouse models and, importantly, in humans with DS, that may contribute to locomotor dysfunction., Competing Interests: The authors have declared that no competing interests exist.

Greater emphasis on the study of intact cellular networks in their physiological environment has led to rapid advances in intravital imaging of the central nervous system (CNS), while the peripheral system remains largely unexplored. To assess large networks of sensory neurons, we selectively label primary afferents with GCaMP6s in male and female C57bl/6 mice and visualize their functional responses to peripheral stimulation in vivo . We show that we are able to monitor the activity of hundreds of sensory neurons simultaneously, with sufficient sensitivity to detect, in most cases, single action potentials with a typical rise time of around 200 ms, and an exponential decay with a time constant of approximately 700 ms. With this technique we are able to characterize the responses of large populations of sensory neurons to innocuous and noxious mechanical and thermal stimuli under normal and inflammatory conditions. We demonstrate that the majority of primary afferents are polymodal with between 50-80% of thermally sensitive DRG neurons responding also to noxious mechanical stimulation. We also specifically assess the small population of peripheral cold neurons and demonstrate significant sensitization to cooling after a model of sterile and persistent inflammation, with significantly increased sensitivity already at decreases of 5°C when compared to uninflamed responses. This not only reveals interesting new insights into the (patho)physiology of the peripheral nervous system but also demonstrates the sensitivity of this imaging technique to physiological changes in primary afferents.

Background: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities., Hypothesis: Baseline LA volume enlargement might predict TZ-related LV dysfunction., Methods: HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population., Results: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m 2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m 2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values., Conclusions: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ., (© 2018 Wiley Periodicals, Inc.)

Ticks (Acari: Ixodidae) are bloodsucking arthropods involved in pathogen transmission in animals and humans. Tick activity depends on various ecological factors such as vegetation, hosts, and temperature. The aim of this study was to analyse the spatial/temporal distribution of ticks in six sites within a peri-urban area of Palermo (Natural Reserve of Monte Pellegrino) and correlate it with field data using Geographical Information System (GIS) data. A total of 3092 ticks were gathered via dragging method from June 2012 to May 2014. The species collected were: Ixodes ventalloi (46.09%), Hyalomma lusitanicum (19.99%), Rhipicephalus sanguineus (17.34%), Rhipicephalus pusillus (16.11%), Haemaphisalis sulcata (0.36%), Dermacentor marginatus (0.10%), and Rhipicephalus turanicus (0.03%). GIS analysis revealed environmental characteristics of each site, and abundance of each tick species was analysed in relation to time (monthly trend) and space (site-specific abundance). A relevant presence of I. ventalloi in site 2 and H. lusitanicum in site 5 was observed, suggesting the possible exposure of animals and humans to tick-borne pathogens. Our study shows the importance of surveillance of ticks in peri-urban areas and the useful implementation of GIS analysis in vector ecology; studies on temporal and spatial distribution of ticks correlated to GIS-based ecological analysis represent an integrated strategy for decision support in public health., Competing Interests: The authors declare no conflict of interest.

Background: Biting midges belonging to Culicoides imicola, Culicoides obsoletus complex and Culicoides pulicaris complex (Diptera: Ceratopogonidae) are increasingly implicated as vectors of bluetongue virus in Palaearctic regions. Culicoides obsoletus complex includes C. obsoletus (sensu stricto), C. scoticus, C. dewulfi and C. chiopterus. Culicoides pulicaris and C. lupicaris belong to the Culicoides pulicaris complex. The aim of this study was a geo-statistical analysis of the abundance and spatial distribution of Culicoides spp. involved in bluetongue virus transmission. As part of the national bluetongue surveillance plan 7081 catches were collected in 897 Sicilian farms from 2000 to 2013., Methods: Onderstepoort-type blacklight traps were used for sample collection and each catch was analysed for the presence of Culicoides spp. and for the presence and abundance of Culicoides vector species (C. imicola, C. pulicaris / C. obsoletus complexes). A geo-statistical analysis was carried out monthly via the interpolation of measured values based on the Inverse Distance Weighted method, using a GIS tool. Raster maps were reclassified into seven classes according to the presence and abundance of Culicoides, in order to obtain suitable maps for Map Algebra operations., Results: Sicilian provinces showing a very high abundance of Culicoides vector species were Messina (80% of the whole area), Palermo (20%) and Catania (12%). A total of 5654 farms fell within the very high risk area for bluetongue (21% of the 26,676 farms active in Sicily); of these, 3483 farms were in Messina, 1567 in Palermo and 604 in Catania. Culicoides imicola was prevalent in Palermo, C. pulicaris in Messina and C. obsoletus complex was very abundant over the whole island with the highest abundance value in Messina., Conclusions: Our study reports the results of a geo-statistical analysis concerning the abundance and spatial distribution of Culicoides spp. in Sicily throughout the fourteen year study. It provides useful decision support in the field of epidemiology, allowing the identification of areas to be monitored as bases for improved surveillance plans. Moreover, this knowledge can become a tool for the evaluation of virus transmission risks, especially if related to vector competence.