Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection: prospective cohort study.

Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann-Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/µL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of -2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08-0.92), p = 0.037; OR 0.30 (0.10-0.88), p = 0.029 and OR 0.19 (0.05-0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS "Advanced grant 5 × 1000, 2021" and by the Italian Ministry of Health "Ricerca Corrente Linea 2".

Risk Awareness as a Key Determinant of Early Vaccine Uptake in the Mpox Vaccination Campaign in an Italian Region: A Cross-Sectional Analysis.

BACKGROUND: we aim to investigate attitudes toward vaccination by analyzing empirical factors associated with vaccine acceptance in the Lazio region mpox vaccination (MpoxVax) campaign in Italy. METHODS: all subjects who accessed MpoxVax and signed the informed consent were prospectively enrolled in the MPOX-VAC Study and were asked to fill out an anonymous survey. Two endpoints were selected: 'delayed acceptance' and 'early acceptance', defined as access for vaccination >60 and ≤30 days from the vaccination campaign starting (VCS), respectively. RESULTS: over the study period, 1717 individuals underwent vaccination: 129 (7%) > 60 [1588 (92.5%) ≤ 60] and 676 (60%) ≤ 30 days from VCS. A bisexual orientation, a lower education level and a worse perceived physical and mental health were associated with delayed access to vaccination. Being pre-exposure prophylaxis (PrEP) users and, marginally, HIV positive; having a high perceived risk for mpox infection; and reporting high-risk behaviors like the use of recreational drugs/chems, sex under the influence of drugs and/or alcohol and having a higher number of principal sexual partners, were associated with early access to vaccination. CONCLUSIONS: according to our data, risk awareness was a major determinant of early MpoxVax acceptance. Conversely, worse perceived health status and a low educational level were critical factors associated with delayed vaccination.

Graphene Photonics I/Q Modulator for Advanced Modulation Formats.

Starting from its classical domain of long distance links, optical communication is conquering new application areas down to chip-to-chip interconnections in response to the ever-increasing demand for higher bandwidth. The use of coherent modulation formats, typically employed in long-haul systems, is now debated to be extended to short links to increase the bandwidth density. Next-generation transceivers are targeting high bandwidth, high energy efficiency, compact footprint, and low cost. Integrated photonics is the only technology to reach this goal, and silicon photonics is expected to play the leading actor. However, silicon modulators have some limits, in terms of bandwidth and footprint. Graphene is an ideal material to be integrated with silicon photonics to meet the requirements of next generation transceivers. This material provides optimal properties: high mobility, fast carrier dynamics and ultrabroadband optical properties. Graphene photonics for direct detection systems based on binary modulation formats have been demonstrated so far, including electro-absorption modulators, phase modulators, and photodetectors. However, coherent modulation for increased data-rates has not yet been reported for graphene photonics yet. In this work, we present the first graphene photonics I/Q modulator based on four graphene on silicon electro-absorption modulators for advanced modulation formats and demonstrate quadrature phase shift keying (QPSK) modulation up to 40 Gb/s.

Autopsies Revealed Pathological Features of COVID-19 in Unvaccinated vs. Vaccinated Patients.

Background: In Italy, by the end of 2021, a new pandemic wave led to increased hospitalizations and death, even in some vaccinated people. We aimed to investigate the death of COVID-19-vaccinated patients who acquired infection and developed severe disease, and to assess differences with fatal COVID-19 in unvaccinated subjects by studying the pathological events triggered by SARS-CoV-2. Methods: Detailed autoptic examination was performed on five fully vaccinated compared to five unvaccinated patients. Histopathological analysis focused on the lung and heart, the two major affected organs. Results: COVID-19 caused, or contributed to death, in all the unvaccinated cases. By contrast, in vaccinated group, pre-existing pathologies played a major role, and death was not COVID-19-related in four out of five patients. These patients did not show the histological features of SARS-CoV-2 lung damage. Diffuse inflammatory macrophages infiltration recently emerged as the main feature of COVID-19 cardiac injury. Interestingly, the most striking difference between the two groups was the absence of increased macrophage infiltration in the heart of vaccinated patients. Conclusions: Results of this study confirm the efficacy of anti-SARS-CoV-2 vaccination in protecting organs from injury and support the need to maintain an adequate immune response by booster dose administration.

Psychological and behavioral characterization of suicide ideators and suicide attempters in adolescence.

Suicide is a global cause of death, a chronic disability, and a significant public health problem. Recent works emphasize the importance of differentiating people with suicide ideation (SI) and people with suicidal attempts (SA), so we conducted a clinical cross-sectional study to better characterize the features most associated with SA. We enrolled 88 adolescents (77 females) from 12 to 18 years of age (M = 15.21, SD = 1.63) admitted to Northern Italian Child Neurology and Psychiatry Service who presented SI and/or SA. We conducted an assessment using the Columbia-Suicide Severity Rating Scale, and divided participants into two groups: adolescents with SA, and adolescents with thoughts about killing themselves which may include a plan but no suicidal attempts (SI). We found that the SA group showed greater severity of SI [t (86) = -3.485, p < 0.001], higher levels of subjective depression [t (70) = -2.65, p = 0.01)], and a higher prevalence of personality disorders [ χ ( 3 ) 2 = 8.775, p = 0.032] than the SI group. Both groups presented a prevalence of internalizing problems compared to the externalizing ones in the Youth Self-Report (YSR). Higher scores on YSR internalizing problems correlate positively with the "Repulsion by Life" subscale of the Multi-Attitude Suicide Tendency (MAST) Scale in both SA and SI groups (p = 0.41 and p = 0.67, respectively), while low levels of the MAST "Attraction to Life" subscale appear more often in the SA one (p = -0.71). In conclusion, results showed that some features (e.g., prevalence of personality disorders, SI intensity, and subjective depression) might help clinicians distinguish between patients with SI and those with SA and support the importance of carefully pursuing this distinction in research.

Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV.

In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-γ production in 216 PLWH on ART with advanced disease (CD4 count <200 cell/mm3 and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm3 (20-122), 93% HIV-RNA < 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (>2 log2 difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.

SARS-CoV-2 Omicron Variant Neutralization after Third Dose Vaccination in PLWH.

The aim was to measure neutralizing antibody levels against the SARS-CoV-2 Omicron (BA.1) variant in serum samples obtained from vaccinated PLWH and healthcare workers (HCW) and compare them with those against the Wuhan-D614G (W-D614G) strain, before and after the third dose of a mRNA vaccine. We included 106 PLWH and 28 HCWs, for a total of 134 participants. Before the third dose, the proportion of participants with undetectable nAbsT against BA.1 was 88% in the PLWH low CD4 nadir group, 80% in the high nadir group and 100% in the HCW. Before the third dose, the proportion of participants with detectable nAbsT against BA.1 was 12% in the PLWH low nadir group, 20% in the high nadir group and 0% in HCW, respectively. After 2 weeks from the third dose, 89% of the PLWH in the low nadir group, 100% in the high nadir group and 96% of HCW elicited detectable nAbsT against BA.1. After the third dose, the mean log2 nAbsT against BA.1 in the HCW and PLWH with a high nadir group was lower than that seen against W-D614G (6.1 log2 (±1.8) vs. 7.9 (±1.1) and 6.4 (±1.3) vs. 8.6 (±0.8)), respectively. We found no evidence of a different level of nAbsT neutralization by BA.1 vs. W-D614G between PLWH with a high CD4 nadir and HCW (0.40 (−1.64, 2.43); p = 0.703). Interestingly, in PLWH with a low CD4 nadir, the mean log2 difference between nAbsT against BA.1 and W-D614G was smaller in those with current CD4 counts 201−500 vs. those with CD4 counts < 200 cells/mm3 (−0.80 (−1.52, −0.08); p = 0.029), suggesting that in this target population with a low CD4 nadir, current CD4 count might play a role in diversifying the level of SARS-CoV-2 neutralization.

Humoral and Cellular Immune Response Elicited by mRNA Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in People Living With Human Immunodeficiency Virus Receiving Antiretroviral Therapy Based on Current CD4 T-Lymphocyte Count.

BACKGROUND: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. METHODS: PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: <200/mm3; intermediate CD4 recovery, ICDR: 200-500/mm3; high CD4 recovery, HCDR: >500/mm3). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. FINDINGS: Among 166 PLWH, after 1 month from the booster dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2%, and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell <200/mm3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ response. As compared with HCWs, PCDR elicited a consistently reduced immunogenicity for all parameters, ICDR only a reduced RBD-binding antibody response, whereas HCDR elicited a comparable immune response for all parameters. CONCLUSION: Humoral and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH, albeit significantly poorer in those with CD4 T-cell <200/mm3 versus those with >500 cell/mm3 and HIV-negative controls. A lower RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm3 was comparable to HIV-negative population.

Impact of Prior Influenza and Pneumoccocal Vaccines on Humoral and Cellular Response to SARS-CoV-2 BNT162b2 Vaccination.

Vaccination against SARS-CoV-2 is considered the most effective method of prevention to contain the pandemic. While highly effective SARS-CoV-2 vaccines are being applied on a large-scale, whether and to what extent the strength of the vaccine-induced immune response could be further potentiated is still an object of debate. Several reports studied the effect of different vaccines on the susceptibility and mortality of COVID-19, with conflicting results. We aimed to evaluate whether previous influenza and/or pneumococcal vaccination had an impact on the specific immune response to the SARS-CoV-2 BNT162b2 mRNA vaccine. The study population consists of 710 workers from our Institute who completed the BNT162b2 schedule and have been tested at least once after the second dose, from 27 December 2020 up to 15 April 2021. Of these, 152 (21.4%) had received an influenza and 215 (30.3%) a concomitant influenza and pneumococcal vaccination, a median of 102 days before the second dose of BNT162b2. Overall, 100% of workers were tested for anti-Spike receptor-binding domain (anti-S/RBD) antibodies, 224 workers for neutralization titer (Micro-neutralization assay, MNA), and 155 workers for a spike-specific T cell interferon-γ response (IFN-γ). The levels of anti-S/RBD, MNA and IFN-γ were evaluated and compared according to sex, age, involvement in direct care of COVID-19 patients, and previous influenza/pneumococcal vaccination. At the univariate analysis, no statistically significant association was observed with regard to a previous influenza and pneumococcal vaccination. A significant lower anti-S/RBD response was observed according to an older age and male sex, while MNA titers were significantly associated to sex but not to age. At the multivariable analysis, workers receiving a concomitant influenza and pneumococcal vaccination or only influenza showed a 58% (p 0.01) and 42% (p 0.07) increase in MNA titers, respectively, compared to those who did not receive an influenza/pneumococcal vaccination. Female workers showed an 81% MNA and a 44% anti-S/RBD increase compared to male workers (p < 0.001). Compared to workers aged 21 to 49 years, those aged 50 or older were associated with a reduction in the anti-S/RBD (16%; p 0.005), MNA (31%; p 0.019), and IFN.g (32%) immune response. Maintaining the influenza and pneumococcal immunization program for the coming season, in which COVID-19 could still be spreading, remains strongly recommended to protect those who are more vulnerable and to limit the potential burden of these infections on the healthcare system.

Ultraviolet C lamps for disinfection of surfaces potentially contaminated with SARS-CoV-2 in critical hospital settings: examples of their use and some practical advice.

BACKGROUND: UltraViolet-C (UV-C) lamps may be used to supplement current hospital cleaning and disinfection of surfaces contaminated by SARS-CoV-2. Our aim is to provide some practical indications for the correct use of UV-C lamps. METHODS: We studied three UV-C lamps, measuring their spatial irradiance and emission over time. We quantify the error that is committed by calculating the irradiation time based exclusively on the technical data of the lamps or by making direct irradiance measurements. Finally, we tested specific dosimeters for UV-C. RESULTS: Our results show that the spatial emission of UV-C lamps is strongly dependent on the power of the lamps and on the design of their reflectors. Only by optimizing the positioning and calculating the exposure time correctly, is it possible to dispense the dose necessary to obtain SARS-CoV-2 inactivation. In the absence of suitable equipment for measuring irradiance, the calculated irradiation time can be underestimated. We therefore consider it precautionary to increase the calculated times by at least 20%. CONCLUSION: To use UV-C lamps effectively, it is necessary to follow a few simple precepts when choosing, positioning and verifying the lamps. In the absence of instruments dedicated to direct verification of irradiance, photochromic UV-C dosimeters may represent a useful tool for easily verifying that a proper UV-C dose has been delivered.

UV-C irradiation is highly effective in inactivating SARS-CoV-2 replication.

The potential virucidal effects of UV-C irradiation on SARS-CoV-2 were experimentally evaluated for different illumination doses and virus concentrations (1000, 5, 0.05 MOI). At a virus density comparable to that observed in SARS-CoV-2 infection, an UV-C dose of just 3.7 mJ/cm2 was sufficient to achieve a more than 3-log inactivation without any sign of viral replication. Moreover, a complete inactivation at all viral concentrations was observed with 16.9 mJ/cm2. These results could explain the epidemiological trends of COVID-19 and are important for the development of novel sterilizing methods to contain SARS-CoV-2 infection.

High-speed double layer graphene electro-absorption modulator on SOI waveguide.

We report on a C-band double layer graphene electro-absorption modulator on a passive SOI platform showing 29GHz 3dB-bandwith and NRZ eye-diagrams extinction ratios ranging from 1.7 dB at 10 Gb/s to 1.3 dB at 50 Gb/s. Such high modulation speed is achieved thanks to the quality of the CVD pre-patterned single crystal growth and transfer on wafer method that permitted the integration of high-quality scalable graphene and low contact resistance. By demonstrating this high-speed CVD graphene EAM modulator integrated on Si photonics and the scalable approach, we are confident that graphene can satisfy the main requirements to be a competitive technology for photonics.

Fingolimod for the treatment of multiple sclerosis in French West Indies, a real-world study in patients from African ancestry.

Affecting 2.5 million people worldwide, multiple sclerosis (MS) is one of the main causes of acquired disability among young adults. In French West Indies (FWI), where MS has arisen from the end of the 80's, a low therapeutic response to interferons beta1 (IFN beta1) in patients of African descent, restrains the therapeutic options. Fingolimod is a Sphingosine-1-Phosphate receptor modulator whose efficacy in the treatment of MS has recently been shown in three phase III studies. Nevertheless, data are currently lacking concerning the use of Fingolimod among populations of African descent, particularly in a real-world setting. Efficacy and safety information collected during the first two years of follow-up have been analysed retrospectively for all patients in whom Fingolimod treatment was introduced in FWI between its marketing date and December 2015. Fifty-two consecutive patients with a relapsing remitting MS started Fingolimod therapy in the FWI, according to the European guidelines. After 24 months, 40 patients were still receiving the treatment. The average Annualized Relapse Rate (ARR) dropped by 81%, and 72.5% of patients remained free from disability progression during the 24 months on Fingolimod. MS remained controlled (according NEDA 3 criteria) for 41% of patients who were still on therapy at 24 months. Nine participants presented with a moderate or major side effect. Unlike IFN beta1 therapy, Fingolimod appears to be effective in Afro-Caribbean patients in a real-world setting with a similar benefit to what has been observed in phase III studies in more selected populations.

Idiopathic Mediastinal Fibrosis: a Systemic Immune-Mediated Disorder. A Case Series and a Review of the Literature.

Mediastinal fibrosis is a rare disease characterised by fibrous proliferation in the mediastinum. It can be idiopathic or secondary to several conditions such as infections and malignancies. Anecdotal reports have described idiopathic mediastinal fibrosis (IMF) in association with other fibro-inflammatory or autoimmune diseases. We report nine new IMF cases recently seen at our Fibro-Inflammatory Disease Clinic and reviewed the IMF cases reported in the English language literature throughout 2006-2016. The purposes of our literature search were to assess the frequency of the association between IMF and other immune-mediated disorders and to analyse which disorders most often coexist with IMF. Of our nine IMF cases, one was associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, one with large-vessel arteritis, three with idiopathic retroperitoneal fibrosis (one of which was IgG4-related), one with pancreatitis and one with IgG4-related seminal vesicle involvement. The remaining two cases, in which IMF was not associated with any other disease, were both classifiable as IgG4-related. The literature review showed that, of the 84 IMF cases identified, 27 (32 %) were associated with other idiopathic autoimmune or fibro-inflammatory disorders, particularly small-vessel vasculitis, Behçet disease, retroperitoneal fibrosis and other conditions belonging to the IgG4-related disease spectrum. Based on our own data and the literature review, we conclude that IMF is often associated with other autoimmune or fibro-inflammatory diseases; therefore, its clinical management requires an accurate screening of associated conditions. Immune-mediated mechanisms may be shared by these disorders.

Assessing executive function with the D-KEFS sorting test: normative data for a sample of the Italian adult population.

One of the major problems in clinical neuropsychology is to apply ecological, easily administrable and sensitive tests that can help in the diagnosis of executive functions. In the present paper we present normative values for the D-KEFS sorting test (ST), exploring the ability of reasoning, categorization abilities, problem solving, flexibility of thinking and abstraction. We collected normative data in a group of 181 normal Italian subjects aged between 20 and 69 years old, matched for educational level. Multiple regression analysis was performed to evaluate the potential effects of age, sex and education. Age and education had a significant effect on ST performance. Our study provided normative data for the D-KEFS ST for the adult Italian population, corrections of raw scores for relevant demographic factors, and percentile grids for both baseline data and on re-testing after 9 months of follow-up. These normative Italian values support the use of the D-KEFS ST as a valid instrument for initial neuropsychological evaluation and longitudinal analysis of executive functions in clinical practice and for research purposes.

p73 G4C14-to-A4T14 gene polymorphism and interaction with p53 exon 4 Arg72Pro on cancer susceptibility: a meta-analysis of the literature.

The p73 gene (1p36-33) is involved in cancer development through cell growth inhibition by inducing apoptosis in a p53-like manner. The p73 G4C14-to-A4T14 dinucleotide polymorphism, consisting of two single-nucleotide polymorphisms in the non-coding region of exon 2 that are in complete linkage disequilibrium, has been extensively studied in association with cancer risk. We performed a meta-analysis of published studies that examined the association between this p73 G4C14-to-A4T14 polymorphism and cancer by searching for relevant studies on Medline and Embase up to February 28, 2010. Pooling data from 19 case-control studies that included 6510 cancer cases and 5711 controls, we found that carriers of the p73 G4C14-to-A4T14 homozygous variant genotype (AT/AT) had an increased global risk of cancer [odds ratio (OR) = 1.30, 95% confidence interval (CI), 1.03-1.65]. There was no evidence of an effect modification of p73 AT/AT by age, gender, ethnicity or smoking status in subgroup analyses; however, a 1.35-fold statistically significant increased risk was found among individuals <55 years old. In case-only analysis, the homozygous p73 G4C14-to-A4T14 variant of p73 genotype was associated with the presence of the p53 exon 4 Arg72Pro allele (OR = 1.30, 95% CI, 1.02-1.64), which is suggestive of a biological interaction between the two genes in carcinogenesis. In conclusion, the p73 G4C14-to-A4T14 homozygous variant genotype might be a risk factor for cancer, especially in combination with the p53 exon 4 Arg72Pro polymorphism. Further studies looking at p73 G4C14-to-A4T14 and p53 exon 4 Arg72Pro interaction are required to support our findings.

Plasmon-enhanced structural coloration of metal films with isotropic Pinwheel nanoparticle arrays.

We experimentally demonstrate angle-insensitive (i.e., isotropic) coloration of nanostructured metal surfaces by engineered light scattering from homogenized Pinwheel aperiodic arrays of gold nanoparticles deposited on gold substrates. In sharp contrast to the colorimetric responses of periodically nanopatterned surfaces, which strongly depend on the observation angle, Pinwheel nanoparticle arrays give rise to intense and isotropic structural coloration enhanced by plasmonic resonance. Pinwheel nanoparticle arrays with isotropic Fourier space were fabricated on a gold thin film and investigated using dark-field scattering and angle-resolved reflectivity measurements. Isotropic green coloration of metal films was demonstrated on Pinwheel patterns, with greatly reduced angular sensitivity and enhanced spatial uniformity of coloration compared to both periodic and random arrays. These findings, which are supported by coupled-dipole numerical simulations of differential scattering cross sections and radiation diagrams, could advance plasmonic applications to display, optical tagging and colorimetric sensing technologies.

Bacterial species present in the lower male genital tract: a five-year retrospective study.

OBJECTIVES: To identify bacterial species present in the lower genital tract of males and to investigate the relationship with semen quality. METHODS: The microscopic analyses and cultures of 696 semen specimens, collected over five years from males investigated for subfertility, were retrospectively assessed. RESULTS: Semen cultures were sterile in 48%; they showed a polymicrobial flora (more than two bacterial species) in 30%, and were positive (>1 × 10(3) colony forming units/ml) in 22% of the cases. Gardnerella vaginalis was the most frequently isolated bacterium, followed by Escherichia coli and Enterococcus sp. Ureaplasma urealyticum was recovered from 13 of 147 samples (9%). Of patients with bacteriospermia 42% had leukospermia (>10(6) leukocytes/ml of semen). Bacteriospermia and leukospermia did not correlate with each other although a positive correlation was found between the presence of leukocytes and G. vaginalis isolation. Semen parameters were correlated with the bacterial species isolated most frequently. In comparison with controls, sperm concentration, motility and morphology were mostly deteriorated in the presence of G. vaginalis and U. urealyticum. CONCLUSIONS: Positive seminal fluid cultures must be interpreted with caution, taking into account both raised colony counts of single isolates and leukocyte concentration in the semen. Thus the common misdiagnosis of genital tract infection, based on the presence of seminal bacteria, and unnecessary treatment with antibiotics may be avoided.

A systematic review evaluating the methodological aspects of meta-analyses of genetic association studies in cancer research.

Meta-analyses and Individual Patient Data (IPD) meta-analyses of genetic association studies are a powerful tool to summarize the scientific evidences, however their application present considerable potential and several pitfalls. We reviewed systematically all published meta-analyses and IPD meta-analyses of genetic association studies in the field of cancer research, searching for relevant studies on the Medline, Embase, and HuGE Reviews Archive databases until January 2009. The association between selected predictors of methodological quality and the year of publication was also evaluated. 144 meta-analyses involving 299 gene-disease associations, and 25 IPD meta-analyses on 83 gene-disease were included. Overall quality of the reports showed a substantial improvement over time, as authors have become more inclusive of primary papers published in all languages since 2005 (P-value = 0.087), as well as statistical heterogeneity and publication bias were evaluated more systematically. Only 35.4% of the meta-analyses, however, adopted a comprehensive bibliographic search strategy to identify the primary reports, 63.9% did not specify the language of the included studies, 39.8% did not test for Hardy-Weinberg Equilibrium (HWE), while 62.2 and 75.9% of the meta-analyses and IPD meta-analyses, respectively, did not declare the scientific rationale for the genetic model chosen. Additionally, the HWE assessment showed a substantial decreasing trend over time (P-value = 0.031) while publication bias was more often evaluated when statistical heterogeneity was actually present (P-value = 0.007). Although we showed a general methodological improvement over time, guidelines on conducting and reporting meta-analyses of genetic association studies are needed to enhance their methodological quality.