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Children are an important target group for influenza vaccination, but few studies have prospectively evaluated influenza vaccine efficacy (VE) in children under 3 years of age. This was a randomized Phase III trial to assess the efficacy, immunogenicity, and safety of an inactivated quadrivalent influenza vaccine (QIV) in young children (EudraCT: 2016-004904-74).Influenza-naïve children aged 6-35 months were randomized during three influenza seasons to receive vaccination with QIV or a non-influenza control vaccine. One group of participants was revaccinated with QIV in the subsequent influenza season. The primary efficacy endpoint was the absolute VE of QIV against influenza caused by any circulating strain. Key secondary efficacy endpoints included the absolute VE of QIV against influenza due to antigenically matching strains and immunogenicity. Safety and reactogenicity were also evaluated.In total, 1005 children received QIV and 995 received control vaccine. Influenza A/B infection due to any circulating influenza strain occurred less frequently in children who received QIV versus children receiving a control vaccine. The absolute VE of QIV against any circulating influenza strain was 54% (95% confidence interval [CI]: 37%, 66%). The absolute VE of QIV against antigenically matching influenza strains was 68% (95% CI: 45%, 81%). Mean hemagglutination inhibition titers for all influenza strains in the QIV group increased post-vaccination, whereas increases were minimal in the control vaccine group; results from virus neutralization and neuraminidase-inhibition assays were generally consistent with the hemagglutination inhibition assay findings. Approximately 12 months after primary vaccination with QIV, antibody titers remained higher than pre-vaccination titers for most strains. In participants who were revaccinated, QIV elicited strong antibody responses. The overall safety profile and reactogenicity of QIV was comparable with control vaccine.Primary vaccination with QIV was well tolerated and effective in protecting children aged 6-35 months against influenza.

Active Noise Control (ANC) methods have been successfully applied to the cancellation of stationary noise. Classical ANC systems use adaptive filtering techniques to produce a waveform that is opposite, or counter-phase, to the signal noise we would like to cancel. However, when the noise is of short duration, adaptive filtering cannot be used since convergence is not achieved. In this paper, a novel active control technique for non-stationary noise is presented. The method uses wave field synthesis (WFS) for the construction of the canceling waveform. The system is tailored for an outdoor environment. The noise acoustic field is acquired by microphones and processed by a WFS engine to pilot a linear array of secondary sources. Experimental results, obtained from both simulations and true tests, demonstrate that the proposed method is able to diminish the overall noise perceived in the area covered by the system.

It is shown that 4-methyl-7-(4-hydroxyphenyl)-[1,2,4]-triazolo[3,2-c][1,2,4]triazole exhibits a rich photoinduced protolytic behavior: Forster cycle shows that the protonated nitrogen of the triazolo-triazole ring is a weak photoacid, with Δ pKa ≈ − 3 ; furthermore, at moderately basic pH its deprotonated monoanion exhibits a long distance water mediated phototautomerism, in which the hydroxyl group releases a proton to solvent and a basic nitrogen of the triazolo-triazole fused ring, different from that protonated in the neutral species, is protonated by the solvent.

Background Enteric parasite infections are underestimated due to the limited sensitivity and specificity of microscopy, which remains the diagnostic gold standard in routine clinical practice. This could be a major problem in high-income countries, where the burden of parasitic diseases is low. In recent years, Multiplex Real-Time polymerase chain reaction (RT-PCR) based methods have been implemented. Therefore, the aim of this study was to evaluate the prevalence of four enteric protozoan species detected by RT-PCR in non-native children in Italy, and to describe their clinical characteristics. Methods Adopted and immigrant children, evaluated for migration health assessment between 2017 and 2020 in a tertiary care children's hospital in Italy, were enrolled. Molecular analysis for Giardia lamblia, Dientamoeba fragilis, Blastocystis hominis, and Entamoeba histolytica, was conducted by in-house RT-PCR. Results Overall, 209 children were enrolled and 70% of them resulted positive by RT-PCR for at least one enteric parasite. B. hominis (47.8%) was the most commonly identified protozoa, followed by D. fragilis (44.5%). Co-infections with multiple pathogens were detected in 35.4% of the samples. Almost 80% of parasite-positive children were asymptomatic and the most common symptom was flatulence (60.7% of symptomatic children). Eosinophils were significantly increased in RT-PCR positive children compared to the negative ones and children with D. fragilis presented the highest eosinophils count. Conclusions The In-house Multiplex RT-PCR assay provides a valid molecular detection system for selected enteric parasites. This novel and accurate diagnostic method can help in increasing the detection rate of parasite infection, especially in high-risk population.

A newly identified coronavirus, named SARS-CoV-2, emerged in December 2019 in Hubei Province, China, and quickly spread throughout the world; so far, it has caused more than 49.7 million cases of disease and 1,2 million deaths. The diagnosis of SARS-CoV-2 infection is currently based on the detection of viral RNA in nasopharyngeal swabs by means of molecular-based assays, such as real-time RT-PCR. Furthermore, serological assays detecting different classes of antibodies constitute an excellent surveillance strategy for gathering information on the humoral immune response to infection and the spread of the virus through the population. In addition, it can contribute to evaluate the immunogenicity of novel future vaccines and medicines for the treatment and prevention of COVID-19 disease. The aim of this study was to determine SARS-CoV-2-specific antibodies in human serum samples by means of different commercial and in-house ELISA kits, in order to evaluate and compare their results first with one another and then with those yielded by functional assays using wild-type virus. It is important to identify the level of SARS-CoV-2-specific IgM, IgG and IgA antibodies in order to predict human population immunity, possible cross-reactivity with other coronaviruses and to identify potentially infectious subjects. In addition, in a small sub-group of samples, a subtyping IgG ELISA has been performed. Our findings showed a notable statistical correlation between the neutralization titers and the IgG, IgM and IgA ELISA responses against the receptor-binding domain of the spike protein. Thus confirming that antibodies against this portion of the virus spike protein are highly neutralizing and that the ELISA Receptor-Binding Domain-based assay can be used as a valid surrogate for the neutralization assay in laboratories that do not have biosecurity level-3 facilities.

Background In recent years, new-onset hypothyroidism was extensively reported in patients receiving sunitinib for malignancy. Effects of sunitinib on serum lipids are not described, however a hyperlipidemic state is commonly observed in hypothyroid patients. Here we report about the incidence and severity of hypercholesterolemia and hypertriglyceridemia in a cohort of patients receiving sunitinib for metastatic renal cell carcinoma. Patients and Methods Thyroid function tests, serum triglycerides, and cholesterol were prospectively evaluated in 39 consecutive metastatic renal cell carcinoma patients, who were receiving sunitinib as a first-line treatment. Incidence of hyperlipidemia, thyroid function impairment, and their possible relationship were investigated. Results Thyroid function tests, serum cholesterol, and triglycerides were assessed at baseline and before the beginning of each sunitinib cycle. During treatment, median triglyceride levels increased up to 271.3 mg/dL, and median cholesterol increased up to 234.7 mg/dL (+113% and +22%, respectively). A hyperlipidemic state developed in 27 patients (69.2%) within a mean time of 1.8 six-week cycles (range, 1-5 cycles) and persisted during treatment. Hypothyroidism was observed in 20 patients (51.2%) and usually developed within 2.3 cycles. Because hypothyroidism and hyperlipidemia developed at different time points of treatment and among different patients, our results failed to demonstrate a correlation between these adverse events. Conclusion New-onset hyperlipidemia was observed in an increased percentage of patients taking sunitinib. The mechanism of this side effect is still unclear. We recommend careful monitoring of serum lipid levels during sunitinib administration to recognize possible consequences, especially on cardiovascular health.

Object Abdominal aortic aneurysm (AAA) pathogenesis remains poorly understood. This study investigated the gene expression profile of peripheral blood from patients with AAA using microarray technology. Methods and results We determined gene expression profiles in pooled RNA from 10 AAA patients and 10 matched controls with arrays representing 14,000 transcripts. Microarray data for selected genes were confirmed by real-time PCR in two different AAA ( n =36) and control ( n =36) populations and integrated with biochemical data. We identified 91 genes which were differentially expressed in AAA patients. Gene Ontology analysis indicated a significant alteration of oxygen transport (increased hemoglobin gene expression) and lipid metabolism [including monoglyceride lipase and low density lipoprotein receptor-related protein 5 ( LRP5 ) gene]. LRP5 expression was associated inversely with serum lipoprotein(a) [Lp(a)] concentration. Conclusions Increased expression of hemoglobin chain genes as well as of genes involved in erythrocyte mechanical stability were observed in the AAA RNA pools. The association between low levels of LRP5 gene expression and increased levels of Lp(a) in AAA patients suggests a potential role of LRP5 in Lp(a) catabolism. Our data underline the power of microarrays in identifying further molecular perturbations associated with AAA.

To compare surgical, pathological, short-term functional data, and complications of endoscopic robotic-assisted simple enucleation (ERASE) and open simple enucleation (OSE).We undertook matched-pair analysis (age, tumor size, and preoperative aspects and dimensions used for an anatomical [PADUA] score) of 392 patients treated with simple enucleation (SE) for T1a-T1b renal tumors in our department, including 160 patients in the OSE group and 80 in the ERASE group. Perioperative outcomes were compared with univariate analysis. Variables associated with warm ischemia time (WIT)25 minutes, complications, and postoperative acute kidney dysfunction (AKD) were assessed with multivariate analysis.The groups were comparable in body mass index (BMI), comorbidity, and preoperative renal function. In the ERASE vs the OSE group, no significant differences resulted regarding WIT (18.5 vs 16.4 minutes, P = .5), complications, transfusion rate, reoperation rate for Clavien grade ≥ 3 complications, and positive surgical margin rate (2.9% vs 2.1%, P = .63). In elective patients, no significant difference resulted in variation of estimated glomerular filtration rate from baseline (8.5 vs 13.9 mL/min, P = .17) and AKD. In the ERASE group, the clamping of renal pedicle was used with a lower frequency (P.0001), with lower estimated blood loss (EBL), longer operative time, and a 1-day shorter hospitalization (P = .001). On the multivariate analysis, the surgical approach was not independently associated with WIT25 minutes, postoperative complications, and AKD.The ERASE is a feasible technique with a positive surgical margin rate comparable to OSE; it showed WIT and complication rates similar to the open approach, along with the advantages of mini-invasivity.

In this paper, the problem of despeckling SAR images when the input data is either an intensity or an amplitude signal is revisited. State-of-the-art despeckling methods based on Bayesian estimators in the wavelet domain, recently proposed in the literature, are taken into consideration. First, how these methods proposed for one format (e.g., intensity) can be adapted to the other format (e.g., amplitude) is investigated. Second, the performance of such algorithms in both cases is analyzed. Experimental results carried out on simulated speckled images and on true SAR data are presented and discussed in order to assess the best strategy. From these results, it can be observed that filtering in the amplitude domain yields better performances in terms of objective quality indexes, such as preservation of structural details, as well as in terms of visual inspection of the filtered SAR data.

Kaposi's sarcoma (KS) is an aggressive, multifocal oncologic disease, which frequently involves skin and internal organs, predominantly affecting homosexual men with AIDS. Hepatic KS is rarely reported in living patients, while autopsies show liver involvement in 35% of patients with KS. Ultrasound (US) of the liver in AIDS patients shows hyperechoic nodules with periportal bands; CT shows a hypodense lesion before and after contrast administration, but in the late phase after iodinated contrast agent injection the nodules are enhanced. Those findings are considered indicative of hepatic KS [1-3].Il sarcoma di Kaposi (KS) è una patologia oncologica multicentrica e aggressiva che coinvolge frequentemente cute e organi interni, prevalentemente in soggetti di sesso maschile e omosessuali affetti da AIDS. Il KS epatico è raramente identificato in pazienti viventi, mentre le autopsie mostrano un coinvolgimento epatico nel 35% dei casi. L’ecografia epatica (US) in pazienti con AIDS mostra noduli iperecogeni con bande periportali, e la scansione TC mostra una lesione ipodensa prima e dopo contrasto, mentre nelle fasi tardive i noduli presentano enhancement. Questi dati sono considerati come indicatori di KS epatico [1–3].

One of the most powerful tools to investigate the structural dynamics of electronically excited molecular systems is visible-pump/mid-infrared-probe spectroscopy. When performing this kind of experiments one must be aware of the artifacts deriving from the non-linear response of the solvent and of the sample cell itself. Cross-phase modulation (XPM) is observed when a strong visible-pump pulse modulates the refraction index seen by the mid-infrared-probe. The effect is enhanced when the probe pulse is chirped and causes the distortion of the transient signal in both the frequency and the time domains. We undertook a detailed simulation of XPM in the mid-infrared region where a visible pulse modulates the MIR pulse by XPM and in close conditions to the experimental ones. Our simulation takes into account the different group velocities of the pump and probe pulses and includes the influence of the linear chirp of the mid-infrared pulse and its asymmetry. The results of our numerical calculations fit very well the experimental signals measured in a 2 mm thick CaF2 window.

Objective Tumor enucleation has been shown to be oncologically safe for elective treatment of renal cell carcinoma (RCC); yet, evidence on long-term oncologic outcomes after robotic tumor enucleation is lacking. In this study we provide a detailed histopathological analysis of tumor–parenchyma interface and the long-term oncologic outcomes after robotic tumor enucleation for sporadic RCC in a high-volume referral center. Materials and Methods We selected consecutive patients undergoing robotic tumor enucleation for sporadic RCC by experienced surgeons with at least 4 years of follow-up. Pattern of pseudocapsule (PC) invasion, thickness of healthy renal margin removed with the tumor, margin status and recurrence rate were the main study endpoints. Multivariable models evaluated independent predictors of PC invasion. Results Overall, 140 patients were eligible for the study. Of these, 127 (91%) had complete data available for analysis. Median thickness of healthy renal margin was 0.57 mm (interquartile range [IQR] 0.24–103). A distinct peritumoral PC was present in 121/127 (95%) tumors with a median thickness of 0.28 mm (IQR 0.14–0.45). In 24/121 (19.8%) cases, RCC showed complete PC invasion. At multivariable analysis, increasing tumor diameter, endophytic rate > 50% and papillary histology were significantly associated with complete PC invasion. Positive surgical margins were reported in 3/127 (2.4%) cases. At a median follow-up of 61 months (range 48–76), one patient died due to metastatic RCC. Among patients alive at follow-up, no cases of recurrence at the enucleation site were recorded, while three cases (2.4%) of renal recurrence (elsewhere in the ipsilateral kidney) and three cases (2.4%) of systemic recurrence were found. Conclusions Distinct RCC-related features were associated with complete PC invasion. By providing a microscopic layer of healthy renal margin in almost all cases, robotic tumor enucleation achieved negative surgical margins in the vast majority of patients, even in case of complete PC invasion. At long-term follow-up, no recurrences were found at the enucleation site. Although our findings need to be confirmed by larger studies with longer follow-up, robotic tumor enucleation appears oncologically safe in experienced hands for the treatment of sporadic RCC.

The Fibrillin-1 gene (FBN1; chromosome 15q21.1) encodes a major glycoprotein component of the extracellular matrix. Mutations in FBN1, TGFBR1, TGFBR2 are known to cause Marfan syndrome (MIM 154700), a pleiotropic disorder. In the present study, we describe five novel missense FBN1 mutations in five Marfan patients that have the peculiarity to activate two contemporary mutational mechanisms: a missense mutation and exon skipping.

Objectives To review the treatment, toxicity, and outcomes in patients with Stage II seminoma after orchidectomy. Materials and methods A retrospective chart review of all patients with Stage II seminoma referred for initial treatment, from 1965 to 2005, was performed. Treatment approaches, toxicity, and outcomes were analyzed. Results A total of 106 patients (83 with Stage IIA, 19 with Stage IIB, and 4 with Stage IIC) were seen between 1965 and 2005. Median age at diagnosis was 36 years (range: 19–71). Median follow-up was 21 years (range: 1.2–42). Eighty-nine patients were treated with adjuvant radiotherapy alone; 13 patients received a combined treatment modality with chemotherapy and radiotherapy after orchidectomy, 4 patients were treated with chemotherapy alone. Generally the treatment was well tolerated, with the main toxicity occurring in patients treated with extended-field radiotherapy. The 5-year disease-specific survival was 96% for the entire group. The 5-year relapse-free survivals for Stages IIA, IIB, and IIC disease were 94%, 72.5%, and 75%, respectively. Fifteen patients developed a relapse and were managed by chemotherapy; 5 of them achieved complete remission and remain free from further recurrence at last follow-up, while 10 died of the disease. Second malignancies were diagnosed in 4 (3.7%) patients during the follow-up. Conclusions In Stage IIA seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Radiotherapy or chemotherapy should be offered as an alternative to Stage IIB patients. Chemotherapy remains the treatment of choice for Stage IIC seminoma.

Background: The oncologic safety of blunt tumor enucleation (TE) of renal cell carcinoma (RCC) depends on the presence of a continuous pseudocapsule (PS) around the tumor and on the possibility of obtaining negative surgical margins (SMs). Objective: To investigate the PS and SMs after TE to define the real need to take a rim of healthy parenchyma around the tumor to avoid the risk of positive SMs. The risk of PS invasion related to other clinical and pathologic variables was also evaluated. Design, setting, and participants: Between September 2006 and December 2007, data were gathered prospectively from 187 consecutive patients who had kidney surgery. Overall, 90 consecutive patients who had TE for RCC were eligible for the study. All specimens were evaluated using an image analyzer by a dedicated uropathologist. Intervention: TE was done by blunt dissection using the natural cleavage plane between the tumor and the normal parenchyma. Measurements: PS,SM, and routinely availableclinical andpathologic variableswere recorded.

Marfan syndrome, a human disease involving cardiovascular and skeletal apparatuses and ocular and central nervous systems, is associated to mutations in FBN1 gene; heterozygous mutations in TGFBR2 and TGFBR1 genes were found associated to MFS type 2, characterized by the presence of skeletal and cardiovascular major criteria and absence of eye major criterion. We screened the TGFBR1 gene in 46 Marfan patients in whom mutations in FBN1 and TGFBR2 genes were excluded and the analysis of Ex1 was extended to additional 114 Marfan patients and 237 controls. We detected two potentially pathological sequence variants: the TGFBR1 6Ala allele whose frequency was higher in the group of Marfan patients (0.13) than in the controls (0.08) (p=0.013; OR=1.69) and an insertion of 20 nucleotides in the 5'UTR that turned out to be a familial silent rare polymorphism. We hypothesize that TGFBR1 sequence variants may act not only as major, but also as low penetrance alleles of the clinical phenotype in Marfan syndrome.

Background In Marfan syndrome, the mitral valve prolapse, ranging from nonclassic to classic form on the basis of the leaflet thickness, is a common condition characterized by a highly variable structural abnormality. We investigated the role of angiotensinogen ( AGT ) M235T, angiotensin converting enzyme ( ACE ) I/D and angiotensin II type 1 receptor ( AT1R ) A1166C polymorphisms in influencing the susceptibility to classic or non-classic mitral valve prolapse in Marfan patients. Methods We studied 135 Marfan patients with mitral valve prolapse, diagnosed by echocardiography. AGT , ACE , and AT1R polymorphisms were identified by polymerase chain reaction-based restriction analysis. Results The frequency of the ACE D, but not AGT 235T and AT1R 1166C allele, was significantly higher in patients with classic mitral valve prolapse in comparison to that observed in the non-classic one ( p =0.03). The percentage of subjects with the contemporaneous presence of ACE D and AGT 235T alleles was significantly higher in the classic mitral valve prolapse group in comparison to the non-classic one (79% vs. 55%, respectively; p =0.008). The concomitant presence of these two alleles was associated with increased susceptibility to the classic mitral valve prolapse ( OR 3.02, p =0.016). Conclusions Our findings show a possible role of ACE and AGT genes as predisposing factors to classic mitral valve prolapse in Marfan patients, thus suggesting a role of renin angiotensin system genes in modulating mitral valve abnormality, and the need for an interventional study with angiotensin II type 1 receptor antagonists, which considers the leaflet thickness progression in Marfan patients with MVP.