Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

THz optical beat-note detection with a fast superconducting hot electron bolometer operating up to 31†GHz.

We study the performance of a hot-electron bolometer (HEB) operating at THz frequencies based on superconducting niobium nitride films. We report on the voltage response of the detector over a large electrical detection bandwidth carried out with different THz sources. We show that the impulse response of the fully packaged HEB at 7.5 K has a 3 dB cutoff around 2 GHz. Remarkably, detection capability is still observed above 30 GHz in an heterodyne beating experiment using a THz quantum cascade laser frequency comb. Additionally, the HEB sensitivity has been evaluated and an optical noise equivalent power NEP of 0.8 pW/√H z has been measured at 1 MHz.

Waveguide integrated hot electron bolometer for classical and quantum photonics.

The development of performant integrated detectors, which are sensitive to quantum fluctuations of coherent light, are strongly desired to realize a scalable and determinist photonic quantum processor based on continuous variables states of light. Here, we investigate the performance of hot electron bolometers (HEBs) fabricated on top of a silicon-on-insulator (SOI) photonic circuit showing responsivities up to 8600 V/W and a record noise equivalent temperature of 1.1 dB above the quantum limit. Thanks to a detailed analysis of the noise sources of the waveguide integrated HEB, we estimate 14.8 dBV clearance between the shot noise and electrical noise with just 1.1µW of local oscillator power. The full technology compatibility with superconducting nanowire single photon detectors (SNSPDs) opens the possibility of nonclassical state engineering and state tomography performed within the same platform, enabling a new class of optical quantum processors.

Single photon detection with superconducting nanowires on crystalline silicon carbide.

Silicon carbide (SiC) is among the most promising optical materials for the realization of classical and quantum photonics, due to the simultaneous presence of quantum emitters and a non-centrosymmetric crystal structure. In recent years, progress have been made in the development of SiC integrated optical components making this a mature platform for the implementation of quantum experiments on chip. Toward this scope, the fabrication of a single photon detector that can be implemented on top of a photonic circuit is essential to achieve a monolithic integration of all the fundamental building blocks required for photonic quantum technologies. Here we demonstrate for the first time single photon detection with superconducting nanowires on top of a bare 3C SiC layer using a novel approach for the fiber-to-detector coupling that allows the optical characterization of multiple detectors without the use of neither cryogenic positioners nor the micromachining of the substrate.

Footprints of BK and JC polyomaviruses in specimens from females affected by spontaneous abortion.

STUDY QUESTION: Are JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) infections associated with spontaneous abortion (SA)? SUMMARY ANSWER: There is no association of JCPyV or BKPyV with SA. WHAT IS KNOWN ALREADY: A large number of risk factors have been associated with SA. The role of polyomaviruses, including JCPyV and BKPyV, in SA remains to be clarified. STUDY DESIGN, SIZE, DURATION: This is a case-control study including women affected by spontaneous abortion (SA, n = 100, the cases) and women who underwent voluntary interruption of pregnancy (VI, n = 100, the controls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Viral DNAs were investigated by qualitative PCR and quantitative droplet-digital PCR (ddPCR) in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from SA (n = 100) and VI (n = 100). Indirect ELISAs with mimotopes/synthetic peptides corresponding to JCPyV and BKPyV viral capsid protein 1 epitopes were then employed to investigate specific IgG antibodies against JCPyV and BKPyV in human sera from SA (n = 80) and VI (n = 80) cohorts. MAIN RESULTS AND THE ROLE OF CHANCE: JCPyV DNA was detected in 51% and 61% of SA and VI samples, respectively, with a mean viral DNA load of 7.92 copy/104 cells in SA and 5.91 copy/104 cells in VI (P > 0.05); BKPyV DNA was detected in 11% and 12% of SA and VI specimens, respectively, with a mean viral DNA load of 2.7 copy/104 cells in SA and 3.08 copy/104 cells in VI (P > 0.05). JCPyV was more prevalent than BKPyV in both SA and VI specimens (P < 0.0001). In PBMCs from the SA and VI cohorts, JCPyV DNA was detected with a prevalence of 8% and 12%, respectively, with a mean viral DNA load of 2.29 copy/104 cells in SA and 1.88 copy/104 cells in VI (P > 0.05). The overall prevalence of serum IgG antibodies against JCPyV detected by indirect ELISAs was 52.5% and 48.7% in SA and VI groups, respectively, whereas BKPyV-positive sera were found in 80% SA and 78.7% VI samples. LIMITATIONS, REASONS FOR CAUTION: This study did not investigate the presence of viral mRNA and/or proteins, which are indicative of an active viral infection, and these might be taken into consideration in future studies. WIDER IMPLICATIONS OF THE FINDINGS: JCPyV and BKPyV DNA sequences were detected and quantitatively analyzed for the first time by PCR/ddPCR in chorionic villi tissues and PBMCs from SA and VI specimens. Moreover specific immunological approaches detected serum IgG against JCPyV/BKPyV. Statistical analyses, however, do not indicate an association between these polyomaviruses and SA. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University of Ferrara, FAR research grants and the University Hospital of Ferrara/University of Ferrara joint grant. No potential conflicts of interest were disclosed.

Osteogenic response and osteoprotective effects in vivo of a nanostructured titanium surface with antibacterial properties.

In implantology, as an alternative approach to the use of antibiotics, direct surface modifications of the implant addressed to inhibit bacterial adhesion and to limit bacterial proliferation are a promising tactic. The present study evaluates in an in vivo normal model the osteogenic response and the osteointegration of an anodic spark deposition nanostructured titanium surface doped with gallium (ASD + Ga) in comparison with two other surface treatments of titanium: an anodic spark deposition treatment without gallium (ASD) and an acid etching treatment (CTR). Moreover the study assesses the osteoprotective potential and the antibacterial effect of the previously mentioned surface treatments in an experimentally-induced peri-implantitis model. The obtained data points out a more rapid primary fixation in ASD and ASD + Ga implants, compared with CTR surface. Regarding the antibacterial properties, the ASD + Ga surface shows osteoprotective action on bone peri-implant tissue in vivo as well as an antibacterial effect within the first considered time point.

Serum antibodies from epileptic patients react, at high prevalence, with simian virus 40 mimotopes.

BACKGROUND AND PURPOSE: It has been demonstrated that inflammation may contribute to epileptogenesis and cause neuronal injury in epilepsy. In this study, the prevalence of antibodies to simian virus 40 (SV40), a kidney and neurotropic polyomavirus, was investigated in serum samples from 88 epileptic children/adolescents/young adults. METHODS: Serum antibodies reacting to specific SV40 peptides were analysed by indirect enzyme-linked immunosorbent assay. Synthetic peptides corresponding to the epitopes of viral capsid proteins 1-3 were used as SV40 antigens. RESULTS: A significantly higher prevalence of antibodies against SV40 was detected in sera from epileptic patients compared to controls (41% vs. 19%). Specifically, the highest significant difference was revealed in the cohort of patients from 1.1 to 10 years old (54% vs. 21%), with a peak in the sub-cohort of 3.1-6 years old (65% vs. 18%). CONCLUSION: Our immunological data suggest a strong association between epilepsy and the SV40 infection.

Modulation of polyfunctional HIV-specific CD8 T cells in patients responding differently to antiretroviral therapy.

Antiretroviral therapy allows a restoration of immune cell homeostasis associated with a normal immune competence. Our goal was to analyze the modulation of polyfunctional HIV-specific CD8+ T-cell responses during antiretroviral therapy. HIV-infected individuals were divided into four groups according to CD4+ cell count and viral load at the moment of recruitment. Whole blood was stimulated with a pool of CD8-specific HIV-antigens to assess cytokine/chemokine production and cytotoxicity activity by using flow cytometry. The groups show different modulation in HIV-specific CD8+ T-cell responses. In particular, immunological failure showed different distributions of polyfunctional HIVspecific CD8+ responses, mainly due to an increase of cells producing CD107alpha/IFNgamma/IL-2/MIP-1beta. Our results indicate that this particular 4+ functional subset is a possible correlate of immunological failure. Considering the complexity of interactions among HAART, immune system and HIV, work is in progress to find correlates of therapy efficacy.

HIV impairs CD34+-derived monocytic precursor differentiation into functional dendritic cells.

Dendritic cells (DCs) perform a basic role in the immune system by allowing the initiation of the primary T-cell-dependent immune response. Given previous indirect evidence that DC maturation and function are impaired by HIV, we have developed an in vitro culture system in order to verify the effect of HIV infection on DC function during the development from hematopoietic progenitors. Considering that monocytic (Mo) differentiating cells efficiently replicate monocytotropic HIV, we examined whether HIV-infected monocytic precursors (MoP) were able to generate functional DCs. CD34+ hematopoietic progenitor cells (HPCs) were induced along Mo differentiative pathway in liquid cultures and at an early stage of culture, MoP were infected with M-tropic BaL HIV strain, and after 2 days they were switched to DC differentiation with GM-CSF and IL-4. Derived DCs were actively infected, as detected by HIV-p24 production. HIV did not significantly affect cell viability, but induced a reduction in cell proliferation and an inefficient functional activity in terms of uptake capability and stimulation of allogenic T cells. These results indicate that HIV-infected MoP lost the capacity to generate functional DCs, and this may represent one of the many mechanisms of immunosuppression exploited by HIV.

Acute abdominal aortic thrombosis caused by paroxysmal atrial fibrillation.

Acute abdominal aortic thrombosis is a rare and potential fatal event, which occurs in adult subjects. We present the case of a 72-year-old-man, who referred to the emergency Department of our hospital because of persistent severe abdominal and perineal pain. Doppler ultrasounds and computerized tomography angiography revealed the acute thrombosis of the abdominal aorta. Immediate revascularization through aortic thrombo-endoarterectomy resolved the disease.

The addition of GnRH antagonists in intrauterine insemination cycles: a pilot study.

AIM: This prospective study was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS) in intrauterine insemination (IUI) treatments. PATIENTS AND METHODS: Eighty patients were divided into two groups: GnRH antagonist group (Group A, n=40) and control group (Group B, n=40). Patients in Group B underwent COS with recombinant Follicle Stimulating Hormone (r-FSH, 50-75 IU/d) only, while patients in Group A were administered r-FSH (50-75 IU/d) plus cetrorelix (0.25 mg/d, starting when ≥ 2 follicles ≥ 14 mm were detected on ultrasound scan). In both groups a single insemination was performed 36 hours after human Chorionic Gonadotropin (hCG, 250 mcg) administration. The primary outcome was clinical Pregnancy Rate (PR). Secondary outcomes were ongoing PR, incidence of Premature Luteinization (PL), number of follicles with mean diameter ≥ 16 mm and between 11 and 15 mm on the day of hCG administration, miscarriage rate, cycle cancellation rate, total amount of r-FSH used and duration of treatment. Student's t test and Chi-square test were used (p < .05 statistically significant). RESULTS: A total of 146 cycles were performed (Group A: n=72; Group B: n=74). A trend towards higher PR in Group A was detected, although it was not statistically significant (Clinical PR: 18.05% vs 10.81%). The number of follicles ≥ 16 mm was significantly increased in Group A. The incidence of both premature LH surge and premature luteinization (PL) was significantly higher in Group B. No significant differences were found in the duration of the stimulation protocol, and in the total amount of r-FSH administered. CONCLUSIONS: The addition of GnRH antagonist in COS/IUI protocol significantly increases the number of mature follicles. However, this multifollicular recruitment is not linked to a significantly higher PR.

Cyclosporine induced generalized hyperkeratosis in a dog.

INTRODUCTION: Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are associated with this medication, however most of them rarely occur. A 5-year-old, female intact French bulldog was presented with multiple, multifocally distributed, severe hyperkeratotic and papillomatous/verrucous plaques. The dog was on long-term immunosuppressive treatment with cyclosporine for meningoencephalitis of unknown origin (MUO). It had an history of atopic dermatitis and calcinosis cutis. A papillomavirus infection was excluded by polymerase chain reaction (PCR), and histopathologic analysis revealed a chronic lymphoplasmacytic non-specific dermatitis, perifolliculitis and periadnexitis and focal folliculitis with papillomatous epidermal hyperplasia and orthokeratotic hyperkeratosis. The diagnosis of "cyclosporine-induced epidermal hyperplasia with secondary pyoderma" was made. Cyclosporine was discontinued and as an alternative mycophenolate mofetil was started to control the MUO. An antimicrobial treatment was prescribed for three weeks. After four months, the skin lesions had healed completely. To date after 2 years, the dog is still in remission. The occurrence of hyperplastic lesions associated with cyclosporine therapy have already been described in previous reports. Most of them resemble those of psoriasiform lichenoid dermatitis, although papilloma virus may be detected in some instances. The dog of the present case showed some peculiarities in the histopathological findings, and a papillomavirus involvement was ruled out with PCR. Like observed in a previous report, there was no correlation between cyclosporine blood level and the severity of dermatological changes. A discontinuation of cyclosporine resulted in complete healing in 4 months. This case highlights the importance of regular monitoring and follow-ups in patients on immunosuppressive therapy. Even rare side effects should always be considered in these cases.

INTRODUCTION: La cyclosporine est un puissant agent immunosuppresseur utilisé en médecine vétérinaire pour traiter une variété de conditions inflammatoires ou à médiation immunitaire. De nombreux effets indésirables sont associés à ce médicament, mais la plupart d'entre eux se produisent rarement. Un bouledogue français intact, âgé de 5 ans, a été présenté avec de multiples plaques hyperkératosiques et papillomateuses/verruqueuses sévères, réparties de manière multifocale. Le chien suivait un traitement immunosuppresseur à long terme à base de cyclosporine pour une méningo-encéphalite d'origine inconnue (MUO). Il avait des antécédents de dermatite atopique et de calcinosis cutis. Une infection à papillomavirus a été exclue par réaction en chaîne par polymérase (PCR) et l'analyse histopathologique a révélé une dermatite chronique lymphoplasmocytaire non spécifique, une périfolliculite et une périannexite ainsi qu'une folliculite focale avec hyperplasie épidermique papillomateuse et hyperkératose orthokératosique. Le diagnostic d'¼hyperplasie épidermique induite par la cyclosporine avec pyodermie secondaire¼ a été posé. La cyclosporine a été stoppée et on a commencé à administrer du mycophénolate mofétil comme alternative pour contrôler l'OMU. Un traitement antimicrobien a été prescrit pendant trois semaines. Après quatre mois, les lésions cutanées étaient complètement guéries. À ce jour, après deux ans, le chien est toujours en rémission. L'apparition de lésions hyperplasiques associées au traitement par la cyclosporine a déjà été décrite dans des rapports précédents. La plupart d'entre elles ressemblent à celles de la dermatite lichénoïde psoriasiforme, bien que le virus du papillome puisse être détecté dans certains cas. Le chien du cas présent présentait quelques particularités dans les résultats histopathologiques et une implication du papillomavirus a été exclue par PCR. Comme observé dans un rapport précédent, il n'y avait pas de corrélation entre le taux sanguin de cyclosporine et la sévérité des altérations dermatologiques. L'arrêt de la cyclosporine a permis une guérison complète en 4 mois. Ce cas souligne l'importance d'une surveillance et d'un suivi réguliers des patients sous traitement immunosuppresseur. Les effets secondaires, même rares, doivent toujours être pris en compte dans ces cas.

Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples of infertile couples correlates with recurrent spontaneous abortion.

STUDY QUESTION: Is the methylation status of the methylenetetrahydrofolate reductase (MTHFR) promoter region in semen samples associated with 'recurrent spontaneous abortion' (RSA)? SUMMARY ANSWER: MTHFR promoter hypermethylation is more frequent in semen samples from RSA couples than in semen samples from infertile couples with no history of RSA (NRSA) and affects the whole sperm population significantly more often. WHAT IS KNOWN ALREADY: Modifications to the MTHFR gene such as polymorphisms and promoter methylations are associated with male infertility. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between 2011 and 2012. MATERIALS, SETTING AND METHODS: DNA from the semen samples of RSA, NRSA and fertile men were analyzed by methylation-specific PCR amplification using primers which anneal to the methylated or unmethylated cytosine-phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR. The specificity of the PCR products was assessed by DNA sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: The methylated MTHFR epigenotype (including samples where it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in the whole sperm population in semen samples from 55% of RSA men compared with 8% in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis was fully concordant with the PCR results and revealed that when MTHFR methylation occurred, CpG islands within the promoter region were 100% methylated (hypermethylation of MTHFR promoter). LIMITATIONS, REASONS FOR CAUTION: The relatively small sample size of RSA infertile couples. WIDER IMPLICATIONS OF THE FINDINGS: The hypermethylation of the MTHFR gene promoter should be taken into consideration as a novel putative risk factor in RSA etiology. STUDY FUNDING/COMPETING INTEREST(S): Our institution has received an FAR research grant from the University of Ferrara, Ferrara, Italy. No competing interests declared.

A novel 8-color flow cytometry panel to study activation, maturation and senescence of CD4 and CD8 T lymphocytes in HIV-infected individuals at different stages of disease.

Multicolor flow cytometry allows to study the markers differentially expressed during maturation, activation, function and senescence on immune cells. Despite the availability of reagents and technology, scarce agreement has been gained regarding phenotypic markers of HIV disease progression other than CD4 T-cell count. In this work, we present a novel high-throughput global analysis of CD4 and CD8 T-lymphocyte profiles by standardized 8-color combinations of antibodies aimed at analyzing HIV disease course progression. For this purpose, two tubes with lyophilized reagent cocktails (CD4- and CD8-specific tubes) were designed to compare the immunological characteristics of HIV-infected persons (37 "high CD4" HAART-treated and 32 "low CD4" naïve or failed-treatment patients) with healthy donors (HD). In particular, T-cell activation (CD25, CD38, CD69), differentiation (CD45RA, CCR7), apoptosis (CD95) and immune suppression profiles (CD25(high)CD127-) in HIV+ patients were compared with HD. Statistical analysis was performed by identifying the parameters associated with disease progression, namely markers that were found to be significantly different between groups with high CD4 counts (including HD) and low CD4 counts (restricted to HIV patients) but not between the HD and the "high CD4" group. This set of markers, including those identifying different maturation and senescence subtypes of CD4 and CD8 T cells, was found to be associated with therapy failure, and it is in fact evaluated in an ongoing study aimed to verify its prognostic value. This robust assay was found feasible on a semi-routine scale for HIV-infected persons, and allows for broader clinical studies aimed at defining markers associated with treatment outcome, possibly having a high impact on the clinical management of HIV disease.

Impact of statins on the coagulation status of type 2 diabetes patients evaluated by a novel thrombin-generation assay.

PURPOSE: Dyslipidemia is common in type 2 diabetes (T2D) and contributes to cardiovascular disease (CVD) by exacerbating atherosclerosis and hypercoagulability. Statins can stabilize atherosclerotic plaque and reduce prothrombotic status. In the present study we aimed to evaluate the coagulation activity and the effect of statins on procoagulant state of T2D patients using a novel activated protein C (APC)-dependent thrombin-generation assay. METHODS: Procoagulant status (by HemosIL ThromboPath (ThP) assay) and in vivo platelet activation (by plasma soluble (s)CD40L levels) were analyzed in a retrospective, cross-sectional study of 198 patients with long-standing T2D and 198 controls. RESULTS: Procoagulant status of T2D patients was enhanced when compared to control subjects (p < 0.0001). Similarly, sCD40L levels were increased in T2D (p < 0.0001). When testing ThP as the dependent variable in a multivariate regression model, sCD40L (p < 0.0001) and statin treatment (p = 0.019) were independent predictors of the procoagulant state of T2D patients. Subgroup analysis showed a significant improvement of coagulability in T2D patients on statins (p = 0.012). CONCLUSIONS: The use of a standardized, easy-to-run, and commercially available APC-dependent thrombin-generation assay detected the presence of a procoagulant status in a large series of patients with long-standing T2D and demonstrated a significant impact of statins in the coagulation status of patients with T2D.

ADMA, SDMA, L-Arginine and nitric oxide in allergic pediatric bronchial asthma.

Published data regarding asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine (L-ARG) and nitric oxide fraction in exhaled air (FeNO) in pediatric bronchial asthma are limited. Many question remain open about plasma concentration of these substances. The aim of this study is to evaluate ADMA, SDMA, L-ARG and FeNO concentration in allergic pediatric mild asthmatic patients in respect to healthy subjects. In this case-control study 60 children (50 asthmatics and 10 healthy) underwent a complete clinical visit, baseline respiratory function, allergy tests and biochemical analyses. The statistical significance of the different concentrations between the two groups were studied using one-way analysis of variance (ANOVA). A p value less than 0.05 was considered statistically significant. The mean plasma ADMA (0.58 vs 0.68 micromol/L), SDMA (0.40 vs 0.45 micromol/L) and L-ARG (52.2 vs 74.13 micromol/L) concentration were significantly lower (p less than 0.001) in the asthmatic patients in respect to healthy subjects (control group). The concentration of FeNO was significantly higher in the asthmatic subjects in respect to the control group (9.18 vs 4.2 micromol/L; p less than 0.001). Low plasma concentrations of ADMA, SDMA, L-ARG and high concentration of FeNO are associated with bronchial asthma and indicate an important role in airway disease through NO metabolism.

Zoledronic acid enhances Vδ2 T-lymphocyte antitumor response to human glioma cell lines.

Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain tumor in humans, responds modestly to treatment: most patients survive less than one year after diagnosis, despite both classical and innovative treatment approaches. A recent paper focused on γδ T-cell response in GBM patients, suggesting the application of an immunomodulating strategy based on γδ T-cells which is already in clinical trials for other tumors. Human Vγ2 T-cells recognize changes in the mevalonate metabolic pathway of transformed cells by activating cytotoxic response, and by cytokine and chemokine release. Interestingly, this activation may also be induced in vivo by drugs, such as zoledronic acid, that induce the accumulation of Vγ2 T-cell ligand Isopentenyl-pyrophosphate by blocking the farnesyl pyrophosphate synthase enzyme. The aim of our work is to confirm whether bisphosphonate treatment would make glioma cell lines more susceptible to lysis by in vitro expanded γδ T-cells, improving their antitumor activity. We expanded in vitro human Vγ2 T-cells by phosphoantigen stimulation and tested their activity against glioma cell lines. Co-culture with glioma cells induced Vγ2 T-cell differentiation in effector/memory cells, killing glioma cells by the release of perforin. Interestingly, glioma cells were directly affected by zoledronic acid; moreover, treatment increased their activating ability on Vγ2 T-cells, inducing an effective antitumor cytotoxic response. Taken together, our results show that aminobisphosphonate drugs may play a dual role against GBM, by directly affecting tumor cells, and by enhancing the antitumor response of Vγ2 T-cells. Our results confirm the practicability of this approach as a new immunotherapeutic strategy for GBM treatment.

Recurrent atrial fibrillation in a patient with ulcerative colitis treated with azathioprine: case report and review of the literature.

We present a clinical case report regarding recurrent atrial fibrillation in a patient with ulcerative colitis treated with azathioprine. Atrial fibrillation represents the most common sustained cardiac arrhythmia, occurring in 1-2% of the general population and characterized by seemingly disorganized atrial depolarizations without effective atrial contraction. Several mechanisms determine this arrhythmia; in particular remodelling (structural, mechanical and electrical alteration related to atrial fibrillation). The pro-arrhythmic effect of azathioprine may be evaluated during immunosuppressive therapy to be aware of this serious but reversible adverse effect.

Lycopene and preclinical carotid atherosclerosis.

Evidence from epidemiological and clinical studies suggests a possible correlation between serum antioxidant levels and cardiovascular disease risk. High plasma concentrations of lycopene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of lycopene in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and twenty subjects underwent physical examination, ultrasonic measurement of common carotid artery intima-media thickness and serum profile analysis. Logistic regression methods and analysis of variance were used to determine whether differences existed between participants with or without evidence of carotid atherosclerosis. Of the 120 participants, 58 exhibited evidence of carotid atherosclerosis. Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly higher serum concentrations of total cholesterol, LDL-cholesterol and triglycerides. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene. These data suggest that higher serum levels of lycopene may play a protective role versus cardiovascular diseases, in particular carotid atherosclerosis.

Agricultural land use curbs exotic invasion but sustains native plant diversity at intermediate levels.

Unveiling the processes driving exotic plant invasion represent a central issue in taking decisions aimed at constraining the loss of biodiversity and related ecosystem services. The invasion success is often linked to anthropogenic land uses and warming due to climate change. We studied the responses of native versus casual and naturalised exotic species richness to land uses and climate at the landscape level, relying on a large floristic survey undertaken in North - Eastern Italy. Both climate and land use drove exotic species richness. Our results suggest that the success of plant invasion at this scale is mainly due to warm climatic conditions and the extent of urban and agricultural land, but with different effects on casual and naturalized exotic species. The occurrence of non-linear trends showed that a small percentage of extensive agricultural land in the landscape may concurrently reduce the number of exotic plant while sustaining native plant diversity. Plant invasion could be potentially limited by land management, mainly focusing on areas with extensive agricultural land use. A more consciousness land management is more and more commonly required by local administrations. According to our results, a shift of intensive to extensive agricultural land, by implementing green infrastructures, seems to be a win-win solution favouring native species while controlling the oversimplification of the flora due to plant invasion.