Corrigendum to "Activation of Melanocortin Receptors MC1 and MC5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy".

[This corrects the article DOI: 10.1155/2016/7368389.].

Assessment of nutritional status and therapy in emergency Medicine settings.

Hospital malnutrition is becoming a clinical concern. Our aim was to determine the prevalence of hospital malnutrition through Nutritional Risk Screening 2002 (NRS) and to evaluate nutritional risk through a prospective study. Nutritional status was assessed collecting anthropometric parameters together with the data relating to the diseases in the medical records of patients admitted to the Department of Emergency Medicine of the "Sant'Eugenio" Hospital. One hundred and sixty patients were retrospectively enrolled during a 3-month observational period. The risk of malnutrition was detected in 52% of patients (of whom 38% at risk and 62% at serious risk). The NRS score was positively correlated with patient age, days between hospital admission and nutritional assessment, disease severity, length of hospital stay and catabolism (p less than 0.05); Basal Energy Expenditure (BEE) and mean arm circumference (MUAC) were negatively correlated with positive outcome (p less than 0.05). No correlations were found in the NRS score, gender, height, weight, Body Mass Index (BMI) and Total Energetic Expenditure (TEE) (p=n.s). A high prevalence of the risk of malnutrition may be detected in the emergency medicine setting, particularly in the geriatric population. The NRS score is not strictly related to BMI, but rather is an excellent tool for disease prognosis, as well as nutritional screening.

Activation of Melanocortin Receptors MC 1 and MC 5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy.

We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12-16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 µL) of the selective MC1 small molecule agonist BMS-470539 (33 µmol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1ß, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment.

Assembly of a photosynthetic reaction center with ABA tri-block polymersomes: highlights on protein localization.

The reconstitution of the integral membrane protein photosynthetic reaction center (RC) in polymersomes, i.e. artificial closed vesicles, was achieved by the micelle-to-vesicle transition technique, a very mild protocol based on size exclusion chromatography often used to drive the incorporation of proteins contemporarily to liposome formation. An optimized protocol was used to successfully reconstitute the protein in a fully active state in polymersomes formed by the tri-block copolymers PMOXA22-PDMS61-PMOXA22. The RC is very sensitive to its solubilizing environment and was used to probe the positioning of the protein in the vesicles. According to charge-recombination experiments and to the enzymatic activity assay, the RC is found to accommodate in the PMOXA22 region of the polymersome, facing the water bulk solution, rather than in the PDMS61 transmembrane-like region. Furthermore, polymersomes were found to preserve protein integrity efficiently as the biomimetic lipid bilayers but show a much longer temporal stability than lipid based vesicles.

Protection from endotoxic uveitis by intravitreal Resolvin D1: involvement of lymphocytes, miRNAs, ubiquitin-proteasome, and M1/M2 macrophages.

This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 µL volume containing 10-100-1000 ng/kg RvD1 1 h post-LPS injection (200 µg, Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-α and NF-κB were reduced.

Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats.

Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10-100-1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 µg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2, N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.

Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry.

BACKGROUND AND AIMS: In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry. METHODS AND RESULTS: From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m(2), n = 22,015), and metabolic control (HbA(1c) ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA1c, diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21-26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27-40% of all discontinuations, after excluding lost to follow-up. HbA1c decreased on average by 0.9-1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0-1.5% with DPP-4 inhibitors. CONCLUSIONS: In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

Inhibition of ocular aldose reductase by a new benzofuroxane derivative ameliorates rat endotoxic uveitis.

The study investigated the effects of the aldose reductase (AR) inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy) benzofuroxane (herein referred to as BF-5m) on the biochemical and tissue alterations induced by endotoxic uveitis in rats. BF-5m has been administered directly into the vitreous, in order to assess the expression and levels of (i) inflammatory markers such as the ocular ubiquitin-proteasome system, NF-κB, TNF-α, and MCP-1; (ii) prooxidant and antioxidant markers such as nitrotyrosine, manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX); (iii) apoptotic/antiapoptotic factors caspases and Bcl-xl; (iv) markers of endothelial progenitor cells (EPCs) recruitment such as CD34 and CD117. 5 µL of BF-5m (0.01; 0.05; and 0.1 µM) into the right eye decreased in a dose-dependent manner the LPS-induced inflammation of the eye, reporting a clinical score 1. It reduced the ocular levels of ubiquitin, 20S and 26S proteasome subunits, NF-κB subunits, TNF-α, MCP-1, and nitrotyrosine. BF-5m ameliorated LPS-induced decrease in levels of MnSOD and GPX. Antiapoptotic effects were seen from BF-5m by monitoring the expression of Bcl-xl, an antiapoptotic protein. Similarly, BF-5m increased recruitment of the EPCs within the eye, as evidenced by CD34 and CD117 antibodies.

Pregnancy effect on disease activity in women with multiple sclerosis treated with cladribine.

INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.

Induced first abortion rates before and after HIV diagnosis: results of an Italian self-administered questionnaire survey carried out in 585 women living with HIV.

OBJECTIVES: The aim of the study was to investigate whether HIV diagnosis affected reproductive planning over time and to assess independent predictors of abortion overall and following HIV diagnosis. METHODS: Donne con Infezione da HIV (DIDI) is an Italian multicentre study based on a questionnaire survey carried out in 585 HIV-positive women between November 2010 and February 2011. The incidence and predictors of abortion were measured by person-years analysis and Poisson regression. RESULTS: The crude incidence rate of abortion was 18.8 [95% confidence interval (CI) 16.5-21.4] per 1000 person-years of follow-up (PYFU). Compared with women who terminated their pregnancy before HIV diagnosis, women who terminated their pregnancy after HIV diagnosis but before 1990 showed a 2.56-fold (95% CI 1.41-4.65) higher risk. During 1990-1999 and 2000-2010, HIV diagnosis was not significantly associated with outcome [adjusted rate ratio (ARR) 0.93 (95% CI 0.55-1.59) and ARR 0.69 (95% CI 0.32-1.48), respectively]. Age [ARR 0.96 (95% CI 0.94-0.99) per 1 year older] and injecting drug use [ARR 1.38 (95% CI 0.98-1.94)] were found to be predictors of abortion overall. After HIV diagnosis, being on combination antiretroviral therapy [ARR 0.54 (95% CI 0.28-1.02)], monthly income < €800 [ARR 1.76 (95% CI 0.99-3.12)], younger age [ARR 0.95 (95% CI 0.91-1.00) per 1 year older] and fear of vertical transmission [ARR 1.95 (95% CI 1.04-3.67)] were found to be independently associated with abortion. CONCLUSIONS: We observed a higher incidence of abortion compared with data available for the general Italian population. Awareness of HIV diagnosis was predictive of abortion only in the 1980s. Women with HIV infection are still worried about vertical HIV transmission. Interventions promoting HIV screening among women who plan to have an abortion and informative counselling on motherhood planning in the setting of HIV care are needed.

No enhancement of fusion probability by the neutron halo of 6He.

Quantum tunnelling through a potential barrier (such as occurs in nuclear fusion) is very sensitive to the detailed structure of the system and its intrinsic degrees of freedom. A strong increase of the fusion probability has been observed for heavy deformed nuclei. In light exotic nuclei such as 6He, 11Li and 11Be (termed 'halo' nuclei), the neutron matter extends much further than the usual nuclear interaction scale. However, understanding the effect of the neutron halo on fusion has been controversial--it could induce a large enhancement of fusion, but alternatively the weak binding energy of the nuclei could inhibit the process. Other reaction channels known as direct processes (usually negligible for ordinary nuclei) are also important: for example, a fragment of the halo nucleus could transfer to the target nucleus through a diminished potential barrier. Here we study the reactions of the halo nucleus 6He with a 238U target, at energies near the fusion barrier. Most of these reactions lead to fission of the system, which we use as an experimental signature to identify the contribution of the fusion and transfer channels to the total cross-section. At energies below the fusion barrier, we find no evidence for a substantial enhancement of fusion. Rather, the (large) fission yield is due to a two-neutron transfer reaction, with other direct processes possibly also involved.

Electrospray technique for solid lipid-based particle production.

BACKGROUND: Different preparation methods for the production of lipid micro- and nanoparticles as controlled release formulations have been widely developed. Novel techniques are attracting increasing attention for their preparation. METHOD: The objective of the present investigation was to produce solid lipid-based micro-nanospheres using the electrohydrodynamic atomization (electrospraying) and to evaluate whether it is a suitable method to prepare drug-loaded particles. RESULTS: Narrowly dispersed spherical particles lower than 1 mum, easily internalized in cells, were obtained using stearic acid and ethylcellulose in a 4.5:0.5 (w/w) ratio. Tamoxifen, as model drug, was encapsulated with good entrapment efficiency. The in vitro release, after an initial burst effect, showed a prolonged drug release. CONCLUSION: The electrospraying method might be proposed to prepare in a single-step monodisperse lipid-based micro- and nanoparticles in powder form for drug delivery.

Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options. OBJECTIVES: The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease. SOURCES: Two databases (PubMed and ClinicalTrial.gov) were reviewed. CONTENT: Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort. IMPLICATIONS: Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the 'off label' use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study.

Effect of suppressing HIV viremia on the HIV progression of patients undergoing a genotype resistance test after treatment failure.

BACKGROUND: Treatment guidelines for multi-experienced HIV patients have recently evolved from aiming to preserve immunity to achieving virological success, largely due to the availability of new antiretroviral drugs and drug classes. To assess the role of viral suppression on clinical progression following a genotypic resistance test (GRT), we have examined a database on patients failing to respond to combined antiretroviral therapy (cART). METHODS: Patients undergoing a GRT after failure to respond to cART between January 1999 and May 2006 were followed up to December 2006. Time-to-death or a new AIDS event/death were considered to be analysis end-points. Viral suppression (< 50 copies/ml [c/ml]) after GRT, a time-dependent covariate, was tested as predictor of disease progression. RESULTS: Overall, 1,389 patients were included in this observational study. After the GRT, patients were followed up to 72 months (median 28 months, IQ range 13-51 months). During the follow-up, 124 patients (9%) died, and 86 (6%) experienced a new AIDS event. 774 patients (56%) achieved < 50 c/ml HIV-RNA. The results of an adjusted Cox model showed that undetectable HIV-RNA after the GRT was significantly associated with a lower risk of death (hazard ration [HR] 0.46, 95% confidence interval [CI] 0.27-0.76) and AIDS/death (HR 0.43, 95% CI 0.28-0.65). The adjusted hazard ratios suggested a twofold risk reduction. A threefold risk reduction of death related to achieved undetectable viral load was found in patients with resistance to more than one drug class and with CDC-C diagnosis; a fourfold reduction was found in patients with < 200 CD4+/mm(3). CONCLUSIONS: Maximal viral suppression has a large impact on HIV progression, particularly in heavily pre-treated individuals. Our findings support the latest treatment guidelines, which have rapidly evolved from an initial lack of indication to suggestions, and finally to strong recommendations for achieving the goal of suppressing viremia.

Soluble proteome investigation of cobalt effect on the carotenoidless mutant of Rhodobacter sphaeroides.

AIMS: To investigate the surviving capability of Rhodobacter sphaeroides under phototrophic conditions in the presence of high cobalt concentration and its influence on the photosynthetic apparatus biosynthesis. METHODS AND RESULTS: Cells from R. sphaeroides strain R26.1 were grown anaerobically in a medium containing 5.0 mmol l(-1) cobalt ions and in a control medium. Metal toxicity was investigated comparing the soluble proteome of Co(2+)-exposed cells and cells grown in control medium by two-dimensional gel electrophoretic analysis. Significant changes in the expression level were detected for 43 proteins, the majority (35) being up-regulated. The enzyme porphobilinogen deaminase (PBGD) was found down-regulated and its activity was investigated. CONCLUSIONS: The up-regulated enzymes mainly belong to the general category of proteins and DNA degradation enzymes, suggesting that part of the catabolic reaction products can rescue bacterial growth in photosynthetically impaired cells. Furthermore, the down-regulation of PBGD strongly indicates that this key enzyme of the tetrapyrrole and bacteriochlorophyll synthesis is directly involved in the metabolic response. SIGNIFICANCE AND IMPACT OF THE STUDY: Data and experiments show that the cobalt detrimental effect on the photosynthetic growth of R. sphaeroides is associated with an impaired expression and functioning of PBGD.

Detection of erythrocyte binding IgM and IgG by flow cytometry in sick dogs with Babesia canis canis or Babesia canis vogeli infection.

The aim of this study was to examine by means of flow cytometry immunophenotyping (FCI) if sick dogs infected with Babesia canis canis (B. c. canis) or Babesia canis vogeli (B. c. vogeli) had anti-erythrocyte membrane binding IgG and/or IgM at the time of diagnosis. Diagnosis of Babesia infection was assessed by blood smear and by PCR-restriction fragment length polymorphism analysis in 30 sick dogs. Signalment, clinical history, physical examination and laboratory tests of B. c. canis (n=24) and of B. c. vogeli (n=6) infected dogs were studied. The majority of B. c. canis infected dogs showed anemia (92%) predominantly non-regenerative (94%), while the B. c. vogeli infected dogs had a regenerative anemia (67%). Eccentrocytosis was present in 33% of the B. c. canis infections. Four of six B. c. vogeli infected dogs had erythrocytes membrane antibodies. One dog resulted uncertain and one resulted negative to FCI. In contrast, all the B. c. canis infected dogs were negative for erythrocytes membrane binding immunoglobulins detection. In addition, the mean percentages of erythrocytes binding IgG and IgM were statistically much lower in B. c. canis than in B. c. vogeli infected dogs. At the time of the diagnosis, the formation of erythrocyte membrane binding IgG and IgM by immune mechanisms appears not to be involved in B. c. canis infections while it is present in the majority of B. c. vogeli infections.

Influence of male human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection on the reproductive outcomes in serodiscordant couples: a case-control study.

BACKGROUND: Nowadays, serodiscordant couples (SDCs) with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)-infected men have the chance to conceive safely, giving birth with a minimum risk of cross-infection. OBJECTIVE: To assess the impact of male HIV and HCV infection on the assisted reproductive technologies (ART) outcomes in SDCs, with HIV or HCV seropositive men and negative partners. MATERIALS AND METHODS: Of 153 couples: 24 in Group 1 (HIV-seropositive men), 60 in Group 2 (HCV-seropositive men) and 69 in Group 3 (controls). Sperm-washing procedure was performed using a three-step system. Fresh ICSI cycles were carried out in HIV SDCs, HCV SDCs and controls. Seminal parameters, fertilization rate (FR), cleavage rate (CR), pregnancy rate per cycle (PR/C), miscarriage rate, implantation rate (IR) and live birth rate were evaluated. RESULTS: All the seropositive men have undetectable viral loads at the time of insemination, and both partners were free from co-morbid infections. The median number of embryos transferred was 2.0 (IQR 1.0-3.0), with no differences among groups. FR was significantly reduced in HIV and HCV SDCs compared to the controls (66%, 61% and 75%, respectively; p < 0.01). CR was similar between groups (p = 0.3). IR was 12.1%, 11.1% and 14.1%, respectively, in the three groups (p = 0.30). PR/C was 21.7%, 17.6% and 20.2% in HIV, HCV and controls, respectively. Live birth rate per cycle was 17.4%, 15.7% and 15.9%, respectively. There were no significant differences in clinical pregnancies per cycle, as well as miscarriages and live births (p = 0.30; 0.30; 0.60, respectively). CONCLUSIONS: The sperm-washing technique with ICSI may generate a promising way to improve pregnancy outcomes and to reduce the risk of viral transmission in these couples. In this setting, we can correctly counsel HIV- and HCV-infected men of SDCs with regard to the likelihood of father their own biological child.

Babesia canis canis and Babesia canis vogeli clinicopathological findings and DNA detection by means of PCR-RFLP in blood from Italian dogs suspected of tick-borne disease.

The aims of this study were to determine the presence of Babesia spp. in blood samples from Italian dogs with clinical signs compatible with tick-borne diseases by means of PCR-restriction fragment length polymorphism (RFLP) and describe the clinicopathological findings of dogs with Babesia infection. We evaluated the majority of canine babesiosis cases by means of clinical history, physical examination, hematological, biochemical, serum electrophoresis, urinalysis and hemostatic tests. Forty-five out of 164 canine blood samples studied were positive to Babesia PCR-RFLP with the following results: Babesia canis canis (n=34) and Babesia canis vogeli (n=11). The majority of B. c. canis infections were detected in Northern Italy (29.1%; 30/103). B. c. vogeli cases were detected mainly in Central and Southern Italy (16.3%; 10/61). Only one B. c. vogeli was detected in Northern Italy (0.9%; 1/103). Three positive samples to B. c. canis and four positive samples to B. c. vogeli were selected for sequencing of a fragment of the 18S rRNA gene (410bp) for further molecular characterization. The sequence obtained from all seven dogs was 99/100% homologous to sequences from B. c. canis and B. c. vogeli, respectively, present in GenBank. Sixty-two percent of dogs infected with B. c. canis had recently travelled on a hunting trip to East European countries. The main acute clinical signs were dehydration, apathy, anorexia and fever. The majority of dogs infected with B. c. canis presented at initial clinical examination mild to severe thrombocytopenia, hyperfibrinogenemia, mild to moderate normocytic-normochromic non-regenerative anemia, hemolysis and neutropenia. The urinalysis showed hemoglobinuria in 13/19 dogs suggesting intravascular hemolysis. Dogs with B. c. canis infection had high levels of C-reactive protein. Hypoalbuminemia was present in 17/26 dogs. The 11 cases of B. c. vogeli infection did not present a homogenous clinicopathological pattern. B. c. vogeli infections were observed in young dogs causing hemolytic anemia and in adult/old does that frequently presented predisposing factors such as splenectomy or immunocompromised conditions. In conclusion, this study demonstrates the presence of B. c. canis and B. c. vogeli in Italian sick dogs and differences in clinicopathological pattern in these two species of B. canis.

Disseminated Scedosporium apiospermum infection in renal transplant recipient: long-term successful treatment with voriconazole: a case report.

Scedosporium apiospermum, the asexual form of Pseudallescheria boydii, is a ubiquitous fungus that represents an unfrequent complication of immune suppression. It accounts for 20% of all non-Aspergillus mold infections in organ transplant recipients. The infection can be localized or disseminated in multiple organs, including lungs, brain, joints, tendons, and skin, and is difficult to treat, due to resistance of S apiospermum to amphotericin B and other antifungal agents. The mortality rate is about 50%. To our knowledge, there are no prospective studies or registries of transplant recipients to guide diagnosis and there are no evidence-based recommendations for the optimal management of this infection. We report a case of S apiospermum infection in a woman with renal transplantation. The first occurrence of infection was a solitary nodule on the forearm, which was surgically excised. Two following relapses were disseminated to the knee, the Achilles tendon, and the skin of the left leg. The infection was successfully treated with voriconazole, but due to the severe iatrogenic immune suppression, a strong reduction in immunosuppressant drugs was needed.

Transcriptomic analysis of nickel exposure in Sphingobium sp. ba1 cells using RNA-seq.

Nickel acts as cofactor for a number of enzymes of many bacteria species. Its homeostasis is ensured by proteins working as ion efflux or accumulation systems. These mechanisms are also generally adopted to counteract life-threatening high extra-cellular Ni2+ concentrations. Little is known regarding nickel tolerance in the genus Sphingobium. We studied the response of the novel Sphingobium sp. ba1 strain, able to adapt to high Ni2+ concentrations. Differential gene expression in cells cultured in 10 mM Ni2+, investigated by RNA-seq analysis, identified 118 differentially expressed genes. Among the 90 up-regulated genes, a cluster including genes coding for nickel and other metal ion efflux systems (similar to either cnrCBA, nccCBA or cznABC) and for a NreB-like permease was found. Comparative analyses among thirty genomes of Sphingobium species show that this cluster is conserved only in two cases, while in the other genomes it is partially present or even absent. The differential expression of genes encoding proteins which could also work as Ni2+-accumulators (HupE/UreJ-like protein, NreA and components of TonB-associated transport and copper-homeostasis systems) was also detected. The identification of Sphingobium sp. ba1 strain adaptive mechanisms to nickel ions, can foster its possible use for biodegradation of poly-aromatic compounds in metal-rich environments.