Lanthanides: Applications in Cancer Diagnosis and Therapy

Lanthanide complexes are of increasing importance in cancer diagnosis and therapy, owing to the versatile chemical and magnetic properties of the lanthanide-ion 4f electronic configuration. Following the first implementation of gadolinium(III)-based contrast agents in magnetic resonance imaging in the 1980s, lanthanide-based small molecules and nanomaterials have been investigated as cytotoxic agents and inhibitors, in photodynamic therapy, radiation therapy, drug/gene delivery, biosensing, and bioimaging. As the potential utility of lanthanides in these areas continues to increase, this timely review of current applications will be useful to medicinal chemists and other investigators interested in the latest developments and trends in this emerging field

SOD2 immunoexpression predicts lymph node metastasis in penile cancer

BACKGROUND: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown. METHODS: SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis. RESULTS: SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis. CONCLUSIONS: Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.Dr. Lara Termini (FAPESP 2005/57274-9); Dr. Luisa Lina Villa (FAPESP 2008/57889-1 and CNPq 573799/2008-3)

Identification of hydrodynamic changes in rivers by means of freshwater mussels' behavioural response: An experimental investigation

The present work concerns the interaction between hydraulic processes and biological communities in rivers. In particular, the aim of this study is to investigate the interactions between flow dynamics and the freshwater mussels (FMs) to verify if the mussels' behavioural response to the hydrodynamic stress could be used to monitor natural extreme events in rivers. Although the influence of mussels on the kinematic characteristics of flow at the water–sediment interface was investigated by a certain number of studies, their behavioural response to flow, both in static and dynamic conditions, remains understudied. Laboratory experiments were performed in an artificial flume exposing Unio elongatulus to different values of flow discharge, both in steady and in unsteady conditions either with or without sediment transport. Mussels' behavioural responses were detected by using Hall sensor technology to measure gaping frequency, amplitude and duration, both in static conditions and under the effect of hydrodynamic stresses. Five categories of behavioural response were identified: Normal Activity (NA), Resting (Re), Transition (Tr), Adaptation (Ad) and Avoidance (Av). During NA (standard feeding and moving), FMs presented valve gaping, while during Re valves were kept constantly opened for water filtration. After a variation of flow discharge (ΔQ), FMs promptly reacted showing a transition from their normal behaviour, with constant gaping frequency (below 0.01 Hz), to higher valve gaping frequencies. The mean valves' gaping frequency increased as a function of ΔQ, and the highest values were reached in the presence of sediment transport. The mean valve opening amplitude was less sensitive to ΔQ. Its range of variation was very narrow with the highest values corresponding to the protrusion/retraction of the animals' foot to move or anchor to the substrate. The percentage of mussels responding to the discharge variation (Transition behaviour) increases with ΔQ confirming that mussels' behavioural response represents a promising tool for monitoring the occurrence of hydrodynamic stressors in fluvial systems

MMP-9/RECK imbalance: a mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus (HPV) and Chlamydia trachomatis

"Manuscript"BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), numbers 2008/03232-1 (to L.L. Villa) and 2012/09746-2 (to M.G. Discacciati and S.S. Maria-Engler) and National Counsel of Technological and Scientific Development pharmaceutical innovation (CNPQ-INCT-if; to S.S. Maria-Engler)

Influence of Bed Roughness on Flow and Turbulence Structure Around a Partially-Buried, Isolated Freshwater Mussel

The present study uses eddy-resolving numerical simulations to investigate how bed roughness affects flow and turbulence structure around an isolated, partially-buried mussel (Unio elongatulus) aligned with the incoming flow. The rough-bed simulations resolve the flow past the exposed part of a gravel bed, whose surface is obtained from a laboratory experiment that also provides some additional data for validation of the numerical model. Results are also discussed for the limiting case of a horizontal smooth bed. Additionally, the effects of varying the level of burial of the mussel inside the substrate and the discharge through the two mussel siphons are investigated via a set of simulations in which the ratio between the median diameter of the (gravel) particles forming the rough bed, d50, and the height of the exposed part of the mussel, h, varies between 0.10 and 0.22. The increase of the bed roughness is associated with a strong amplification of the turbulence kinetic energy in the near-wake region. Increasing the bed roughness and/or reducing h intensifies the interactions of the eddies generated by the bed particles with the base and tip vortices induced by the active filtering and by the mussel shell, respectively, which, in turn, induces a more rapid dissipation of these vortices. Increasing the bed roughness also reduces the strength of the main downwelling flow region forming in the wake. The strong downwelling near the symmetry plane is the main reason why the symmetric wake shedding mode dominates in the smooth bed simulations with negligible active filtering. By contrast, the anti-symmetric wake shedding mode dominates in the simulations conduced with a high value of the bed roughness. The mean streamwise drag force coefficient for the emerged part of the shell and the dilution of the excurrent siphon jet increase with increasing bed roughness

Formation of wood obstructions at bridges: processes, related problems and prediction tools

The primary cause of many bridge collapses is related to hydraulic issues, and the Italian technical standards for constructions (NTC 2018) offer limited guidance on the design and verification criteria for bridges, especially concerning river processes. Recognizing this gap, a working group dedicated to 'Hydraulic Compatibility of Bridges' (sites.google.com/view/gii-ponti) was established in 2021. The group's objective is to develop proposals for good practices and guidelines that assess bridge hydraulic compatibility, providing a foundation for both bridge safety and flood risk analysis. Within this initiative, a working subgroup focused on 'floating debris' is striving to define a methodology for assessing the impacts of wood accumulation on bridges. While wood in rivers is environmentally beneficial, its transport and accumulation at bridges during high-stage events can lead to problematic consequences. Over the past two decades, the scientific community has actively studied wood transport dynamics, accumulation formation at bridges, and their effects on hydraulics and structural stability. Although some methodologies to assess wood-related risk have been incorporated into national legislation or practitioner reports, these implementations vary widely in defining the shape of accumulation, the wood volume assessment and the number of parameters considered. In many cases, qualitative evaluations are used for estimation due to the complexity and high site specificity inherent in wood transport dynamics. This work aims to propose a comprehensive approach, based on the latest research findings, (i) to define the wood accumulation probability at a bridge, (ii) to estimate the size and position of the accumulation, and (iii) to suggest a methodology for the estimation of bridge scour induced by wood accumulation

[Anti-Pseudomonas aeruginosa antibodies and lung disease in cystic fibrosis]

The aim of our study was to diagnose and to control three aspects of the evolution of lung disease in CF: the absence of infection, the intermittent colonization and chronic infection by Pseudomonas aeruginosa. Therefore a study of anti-pseudomonas antibodies (Ab) (anti-protease, anti-elastin and antihexo-toxin A) for diagnosis and follow-up of CF patients was considered. Moreover, we related the presence of Ab to the sputum culture, to FEV1, to patient age and to genotype. Tbe Ab were dosed in 121 patients by quantitative ELISA method. Values < 1: 500 were considered negative, values> 1: 500 and < 1:1250 borderline, and > 1:1250 positive. 16.5% of patients did not have Ab, 17% had borderline values and 69.5% had positive values. All the patients with negative Ab had negative sputum culture; 47% of patients with borderline values had at least one positive culture while 53% were negative. 87% of patients with positive values had chronic colonization, 13% intermittent colonization. The increase in the Ab rate is statistically related to a more severe lung disease (p < 0.013). The presence of a severe mutation (?F 508) is related to positive values of Ab. Evaluation of anti-Pseudomonas aeruginosa is an important tool for diagnosis and follow-up of CF lung diseas

Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE

: Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping