Weathering increases the acute toxicity of plastic pellets leachates to sea-urchin larvae-a case study with environmental samples.

Microplastics, particles under 5 mm, pervade aquatic environments, notably in Tarragona's coastal region (NE Iberian Peninsula), hosting a major plastic production complex. To investigate weathering and yellowness impact on plastic pellets toxicity, sea-urchin embryo tests were conducted with pellets from three locations-near the source and at increasing distances. Strikingly, distant samples showed toxicity to invertebrate early stages, contrasting with innocuous results near the production site. Follow-up experiments highlighted the significance of weathering and yellowing in elevated pellet toxicity, with more weathered and colored pellets exhibiting toxicity. This research underscores the overlooked realm of plastic leachate impact on marine organisms while proposes that prolonged exposure of plastic pellets in the environment may lead to toxicity. Despite shedding light on potential chemical sorption as a toxicity source, further investigations are imperative to comprehend weathering, yellowing, and chemical accumulation in plastic particles.

Long-Term Survival Analysis of Pleural Mesothelioma Patients Undergoing Surgery: Brief Report From a Tertiary Referral Centre.

OBJECTIVES: to date, no consensus has been reached on the surgical gold-standard in pleural mesothelioma (PM). We retrospectively reviewed our experience as a tertiary referral centre, to compare short- and long-term survival of PM patients undergoing different types of surgery. METHODS: in retrospective, observational, single-centre study, we analysed all the patients histologically diagnosed with PM undergoing surgical procedures with palliative or curative intent at IRCCS Istituto Nazionale dei Tumori of Milan, Italy, from January 2003 to December 2020. The primary study endpoint was 10-year overall survival (OS) in three different types of resections: extra-pleural-pneumonectomy (EPP), pleurectomy/decortication (P/D), partial-pleurectomy/pleural-biopsy (PP/B). Secondary endpoints were postoperative hospital stay and postoperative 30-day and 90-day mortality rates. The survival function was estimated using Kaplan-Meier, and the Log-rank test was used for testing differences. Univariable and Multivariable Cox regression models were implemented to estimate Hazard Ratio (HR) for all variables of interest. RESULTS: 243 consecutive patients were enrolled, EPP was performed in 49 (20.2%), P/D in 58 (23.8%), PP/B in 136 (56.0%) patients. The median follow-up time was 19.8 months. 10-year OS was significantly better for P/D group (16%, Log-Rank test p<0.0001) compared to PP/B (1.8%) and EPP (0%). No statistically significant differences were found among the 3 surgical groups in 30- and 90-day mortality rates. At multivariable analysis, gender (male, HR=1.58), type of resection (P/D, HR=0.55) and surgery date (recent years, HR=0.61) were found to be independent prognostic factors for OS. CONCLUSIONS: in PM, lung-sparing curative approach (e.g. P/D) should be preferred in highly selected patients and in highly experienced centres, whenever appropriate. Anyway, when P/D is not indicated, adopting palliative/conservative management (e.g. PP/B) could ensure comparable results as extremely aggressive surgeries (e.g. EPP). The aim of surgery in PM should not be reaching complete resection, but rather accomplishing significant resection allowing to complete the multimodality treatment in highly selected patients in experienced centers.

Short-term exposition to acute cadmium toxicity induces the loss of root gravitropic stimuli perception through PIN2-mediated auxin redistribution in Arabidopsis thaliana (L.) Heynh.

Cadmium (Cd), one of the most widespread and water-soluble polluting heavy metals, has been widely studied on plants, even if the mechanisms underlying its phytotoxicity remain elusive. Indeed, most experiments are performed using extensive exposure time to the toxicants, not observing the primary targets affected. The present work studied Cd effects on Arabidopsis thaliana (L.) Heynh's root apical meristem (RAM) exposed for short periods (24 h and 48 h) to acute phytotoxic concentrations (100 and 150 µM). The effects were studied through integrated morpho-histological, molecular, pharmacological and metabolomic analyses, highlighting that Cd inhibited primary root elongation by affecting the meristem zone via altering cell expansion. Moreover, Cd altered Auxin accumulation in RAM and affected PINs polar transporters, particularly PIN2. In addition, we observed that high Cd concentration induced accumulation of reactive oxygen species (ROS) in roots, which resulted in an altered organization of cortical microtubules and the starch and sucrose metabolism, altering the statolith formation and, consequently, the gravitropic root response. Our results demonstrated that short Cd exposition (24 h) affected cell expansion preferentially, altering auxin distribution and inducing ROS accumulation, which resulted in an alteration of gravitropic response and microtubules orientation pattern.

Super Liquid-repellent Surfaces and 3D Spheroids Growth.

Substrates composition and surface features of materials rule adhesion control of cells to surfaces. As a result, most of the aspects of cell functions, such as spreading, migration, proliferation, and differentiation, can be significantly influenced in biomedical applications. Cell cultures make possible to understand cell biology, tissue morphology, mechanisms of diseases, drug action, and tissue engineering development, among others. Recent techniques related to culturing 3D cell aggregates in the presence of very low wettable surfaces represent an innovative field for in vitro experimentation aimed at more reliable conditions to investigate both tumor and non-tumor cell lines. Matching in particular cell biology to innovative materials, this work reviews the recent literature available on promoting cell aggregates formation strongly influenced by the high surface hydrophobicity. In particular, for spheroid formation, the highest water repellent coatings seem to be required for the significant effectiveness of the process. In this way, 3D cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions.

Lung response to prone positioning in mechanically-ventilated patients with COVID-19.

BACKGROUND: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population. METHODS: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity. RESULTS: By the time of the study, PEEP was 12 (10-14) cmH2O and the PaO2:FiO2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001). CONCLUSIONS: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.

Mammalian Cell Spheroids on Mixed Organic-Inorganic Superhydrophobic Coating.

Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface hydrophobicity strongly influences the promotion of cell aggregate formation. In particular, for spheroid formation, highly water-repellent coatings seem to be required for the significant effects of the process. In this work, surfaces at different wettability have been compared to observe their influence on the growth and promotion of aggregates of representative mammalian cell lines, both tumoral and non-tumoral (3T3, HaCat and MCF-7 cell lines). The effect of increased hydrophobicity from TCPS to agarose hydrogel to mixed organic-inorganic superhydrophobic (SH) coating has been investigated by optical and fluorescence microscopy, and by 3D confocal profilometry, in a time scale of 24 h. The results show the role of less wettable substrates in inducing the formation of spheroid-like cell aggregates at a higher degree of sphericity for the studied cell lines.

Management of intrathoracic phosphaturic mesenchymal tumor by nonintubated uniportal video-assisted thoracic surgery in a fragile patient.

BACKGROUND: Phosphaturic mesenchymal tumors are rare neoplasms, frequently presenting with osteomalacia. These neoplasms usually grow at a slow rate and are associated with unspecific symptoms. CASE: In this study, we present the case of a 70-year-old woman who had been suffering from musculoskeletal pain, hypophosphatemia, and spontaneous fractures. Positron emission tomography with Gallium showed increase uptake in a subpleural lesion. CONCLUSION: The patient underwent surgical excision of the subpleural lesion with a non-intubated uniportal video-assisted thoracoscopic surgery approach.

The role of sonographic patterns during endobronchial ultrasound-transbronchial needle aspiration for lung cancer staging: a narrative review.

In lung cancer accurate assessment of the mediastinal lymph node status is of paramount importance for the stage assignment as well as crucial for the therapeutic plan. TAC and positron emission tomography (PET) are valuable tools to achieve a preliminary picture of the mediastinal staging but Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is considered the first choice for investigating mediastinal lymph nodes as recommended by updated guide-lines. Despite the EBUS-TBNA sensitivity is satisfactory, it is not high enough to exclude mediastinal lymph node metastases; therefore devices and technologies were implemented to increase its sensitivity. The purpose of this narrative review is to describe the tools aimed at correctly interpreting sonographic patterns during EBUS and maximizing the diagnostic accuracy of TBNA. The bibliographic research identified 354 articles potentially related to the purpose of the current review and after accurate reading we selected 21 articles. Eight articles focused on the sonographic features of lymph nodes found during EBUS, 2 papers considered the Doppler patterns and, finally, 18 studies analyzed the advantages of ultrasound elastography. Sonographic features, vascular patterns and ultrasound elastography have proved to be helpful in directing the operator to biopsy the most suspect lymph node, especially in patients with CT-negative and/or PET-negative mediastinum.

3D profilometry and cell viability studies for drug response screening.

In vitro tests for assessing cell viability and drug response are widely employed for determining cytotoxicity of drugs, chemicals, or material substrates. These assays have some advantages, such as speed, reduced cost, and potential for automation. However, since these tests are often run with a huge amount of cells, the characteristic properties of a single cell can be masked leading to a lack of the diagnostic features of these assays. Vital processes as proliferation and cell death (either necrosis or apoptosis) are associated to drastic changes of volume and surface analysis techniques like 3D optical scanning profilometry allow noninvasive and nondestructive approach with fast detection and good resolution at nano-microscale. Here, we demonstrate how coupling noninvasive morphological surface analysis techniques with well assessed biochemical methods can help to establish the relationship between the modifications on cellular viability induced by precursors of proliferation and cell death and variations on cell volume induced by these treatments. The proposed approach has demonstrated improved efficiency on the assessment of inductive changes on tumoral cells in comparison to non-tumoral cells upon administration of proliferative nontoxic or cytotoxic substances like chemotherapeutics.

Mammalian cell viability on hydrophobic and superhydrophobic fabrics.

Surface properties like hydrophobicity and morphology of the substrate are essential for cell proliferation affecting its growth, survival and also for its communication with other cells on fabrics. The combination of low surface energy and a specific surface morphology (micro/nano-roughness) leads to significantly less wettable surfaces, known as superhydrophobic characterized by high contact angle above 150° and a very small hysteresis. Such high water repellent coatings feature small area available to be exploited in many applications where interactions with aqueous environment are strongly to be avoided. In this work, the authors have investigated the influence of coating polyester fabric at different degree of hydrophobicity by mixed organic-inorganic coating with moderated to highly water repellence. Depending on the coating composition and structure, the hydrophobicity of the fabric can be finely modulated by an easy-to-prepare method applicable to commercial, low cost fabric substrates providing advanced performance. In vitro experiments have been performed in order to establish the influence of surface modification on adhesion of representative model mammalian cell lines such as 3T3 fibroblasts, HaCaT keratinocytes and HeLa epithelial carcinoma cells. The obtained results suggested that, in addition to the chemistry and morphology of the coating, the characteristics of the substrate are important parameters on the final cell viabilities.

Impaired hypoxic pulmonary vasoconstriction in a mouse model of Leigh syndrome.

Hypoxic pulmonary vasoconstriction (HPV) is a physiological vasomotor response that maintains systemic oxygenation by matching perfusion to ventilation during alveolar hypoxia. Although mitochondria appear to play an essential role in HPV, the impact of mitochondrial dysfunction on HPV remains incompletely defined. Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4-/-) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children. Breathing normobaric 11% O2 prevents neurological disease and improves survival in Ndufs4-/- mice. In this study, we found that either genetic Ndufs4 deficiency or pharmacological inhibition of CI using piericidin A impaired the ability of left mainstem bronchus occlusion (LMBO) to induce HPV. In mice breathing air, the partial pressure of arterial oxygen during LMBO was lower in Ndufs4-/- and in piericidin A-treated Ndufs4+/+ mice than in respective controls. Impairment of HPV in Ndufs4-/- mice was not a result of nonspecific dysfunction of the pulmonary vascular contractile apparatus or pulmonary inflammation. In Ndufs4-deficient mice, 3 wk of breathing 11% O2 restored HPV in response to LMBO. When compared with Ndufs4-/- mice breathing air, chronic hypoxia improved systemic oxygenation during LMBO. The results of this study show that, when breathing air, mice with a congenital Ndufs4 deficiency or chemically inhibited CI function have impaired HPV. Our study raises the possibility that patients with inborn errors of mitochondrial function may also have defects in HPV.

Real-time urinary electrolyte monitoring after furosemide administration in surgical ICU patients with normal renal function.

BACKGROUND: Although the loop-diuretic furosemide is widely employed in critically ill patients with known long-term effects on plasma electrolytes, accurate data describing its acute effects on renal electrolyte handling and the generation of plasma electrolyte alterations are lacking. We hypothesized that the long-term effects of furosemide on plasma electrolytes and acid-base depend on its immediate effects on electrolyte excretion rate and patient clinical baseline characteristics. By monitoring urinary electrolytes quasi-continuously, we aimed to verify this hypothesis in a cohort of surgical ICU patients with normal renal function. METHODS: We retrospectively enrolled 39 consecutive patients admitted to a postoperative ICU after major surgery, and receiving single low-dose intravenous administration of furosemide. Urinary output, pH, sodium [Na(+)], potassium [K(+)], chloride [Cl(-)] and ammonium [NH4 (+)] concentrations were measured every 10 min for three to 8 h. Urinary anion gap (AG), electrolyte excretion rate, fractional excretion (Fe) and time constant of urinary [Na(+)] variation (τNa(+)) were calculated. RESULTS: Ten minutes after furosemide administration (12 ± 5 mg), urinary [Na(+)] and [Cl(-)], and their excretion rates, increased to similar levels (P < 0.001). After the first hour, urinary [Cl(-)] decreased less rapidly than [Na(+)], leading to a reduction in urinary AG and pH and an increment in urinary [NH4 (+)] (P < 0.001). Median urinary [Cl(-)] over the first 3-h period was higher than baseline urinary and plasmatic [Cl(-)] (P < 0.001). During the first 2 h, difference between FeCl(-) and FeNa(+) increased (P < 0.05). Baseline higher values of central venous pressure and FeNa(+) were associated with greater increases in FeNa(+) after furosemide (P = 0.03 and P = 0.007), whereas higher values of mean arterial and central venous pressures were associated with a longer τNa(+) (P < 0.05). In patients receiving multiple administrations (n = 11), arterial pH, base excess and strong ion difference increased, due to a decrease in plasmatic [Cl(-)]. CONCLUSIONS: Low-dose furosemide administration immediately modifies urinary electrolyte excretion rates, likely in relation to the ongoing proximal tubular activity, unveiled by its inhibitory action on Henle's loop. Such effects, when cumulative, found the bases for the long-term alterations observed. Real-time urinary electrolyte monitoring may help in tailoring patient diuretic and hemodynamic therapies.

Toxicity study in blood and tumor cells of laser produced medicines for application in fabrics.

Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions in water at 20mg/mL concentration to increase antibacterial activity of resulting mixtures. Compared to previous results obtained on bacteria, more research is needed about UV laser irradiated phenothiazines applications on cancer cell cultures to evidence possible anticancerous properties. Evaluation of the safety of the newly obtained photoproducts in view of use on humans is also needed. Due to expensive animal testing in toxicology and pressure from general public and governments to develop alternatives to in vivo testing, in vitro cell-based models are attractive for preliminary testing of new materials. Cytotoxicity screening reported here shows that laser irradiated (4h exposure time length) chlorpromazine and promazine are more efficient against some cell cultures. Interaction of laser irradiated phenothiazines with fabrics show that promethazine and chlorpromazine have improved wetting properties. Correlation of these two groups of properties shows that chlorpromazine appears to be more recommended for applications on tissues using fabrics as transport vectors. The reported results concern stability study of phenothiazines water solutions to know the time limits within which they are stable and may be used.

Carbon Soot-Ionic Surfactant Mixed Layers at Water/Air Interfaces.

An experimental study is here presented on the properties of aqueous dispersions containing carbon nanoparticles and different ionic surfactants which can modify the degree of hydrophobicity/philicity of particles favoring their transfer from the dispersion bulk to the interfacial layer. Aim of this work is to understand the particle-surfactant and particle-fluid interface interactions and their effect on those macroscopic surface properties of the mixed systems which are expected related to the stability and structure of the respective particle stabilized foams. To this purpose a systematic characterization of dispersions have been carried out, based on surface tension measurement against the surfactant concentration, using a drop Profile Analysis Tensiometer (PAT). These results have been crossed with the characterization of the bulk dispersion by Dynamic Light Scattering (DLS) and ζ-potential measurements to check the effects of surfactant on the particle aggregation and on the particle surface charge, respectively. The stability of the foams obtained with the same compositions has been also investigated and correlated to the other surface and bulk properties.

Melanoma primário de mama: relato de caso / Primary breast melanoma: case report

O melanoma primário de mama em sítio parenquimatoso é um tumor raro. Por sua baixa incidência, desconhece-se sua apresentação clínica usual, a evolução natural da doença, bem como resposta ao tratamento e seu prognóstico. É por esse motivo que se faz necessária uma boa investigação diagnóstica a fim de se obter precocemente o diagnóstico correto para se estabelecer a abordagem terapêutica adequada para cada paciente. Desse modo, relata-se o caso de paciente feminino, 61 anos, branca, encaminhada devido a nódulo palpável em mama direita e alteração mamográfica com BI-RADS 3, que teve diagnóstico de melanoma de parênquima mamário confirmado por exame anatomopatológico complementado por estudo imuno-histoquímico. Assim, com o objetivo desse trabalho de alcançar uma maior compreensão do assunto para que casos semelhantes a esse sejam futuramente abordados de maneira precoce e que garanta ao paciente o melhor cuidado, serão discutidos os aspectos relacionados à incidência do melanoma de mama, às dificuldades diagnósticas, ao prognóstico e às abordagens terapêuticas.

Primary melanoma in breast parenchyma is a rare tumor. Because of its low incidence, it is unknown its usual clinical presentation, the natural course of the disease and its response to treatment and prognosis. For this reason, a good diagnostic investigation is necessary in order to get the correct diagnosis as soon as possible to establish the appropriate therapeutic approach for each patient. Thus, we report a female patient case, 61 years-old, white, referred due to a palpable mass in the right breast and a mammographic alteration that shows BI-RADS 3, who had breast parenchyma melanoma diagnosed and confirmed by pathological examination complemented by immunohistochemical study. Under these circumstances, with the objective of this work to achieve a greater understanding of the subject so that such cases are identified as early as possible in the future and ensure the best patient care, aspects related to the incidence of breast melanoma, diagnostic difficulties, prognostic and therapeutic approaches will be discussed.

Human aldo-keto reductase AKR7A2 protects against the cytotoxicity and mutagenicity of reactive aldehydes and lowers intracellular reactive oxygen species in hamster V79-4 cells.

Aldo-keto reductase (AKR) enzymes are critical for the detoxication of endogenous and exogenous aldehydes. Previous studies have shown that the AKR7A2 enzyme is catalytically active toward aldehydes arising from lipid peroxidation, suggesting a potential role against the consequences of oxidative stress, and representing an important detoxication route in mammalian cells. The aim of this study was to determine the ability of AKR7A2 to protect cells against aldehyde cytotoxicity and genotoxicity and elucidate its potential role in providing resistance to oxidative stress. A transgenic mammalian cell model was developed in which AKR7A2 was overexpressed in V79-4 cells and used to evaluate the ability of AKR7A2 to provide resistance against toxic aldehydes. Results show that AKR7A2 provides increased resistance to the cytotoxicity of 4-hydroxynonenal (HNE) and modest resistance to the cytotoxicity of trans, trans-muconaldehyde (MUC) and methyglyoxal, but provided no protection against crotonaldehyde and acrolein. Cells expressing AKR7A2 were also found to be less susceptible to DNA damage, showing a decrease in mutation rate cause by 4-HNE compared to control cells. Furthermore, the role of the AKR7A2 enzyme on the cellular capability to cope with oxidative stress was assessed. V79 cells expressing AKR7A2 were more resistant to the redox-cycler menadione and were able to lower menadione-induced ROS levels in both a time and dose dependent manner. In addition, AKR7A2 was able to maintain intracellular GSH levels in the presence of menadione. Together these findings indicate that AKR7A2 is involved in cellular detoxication pathways and may play a defensive role against oxidative stress in vivo.

The role of ultrasound-guided aspiration biopsy of peripheral pulmonary nodules: our experience.

BACKGROUND: Peripheral lung lesions are difficult to diagnose with conventional methods: ultrasound-guided aspiration biopsy is an interesting prospect having been reported to have good sensitivity and specificity. PATIENTS AND METHODS: From January 1991 to August 2001 we investigated, in 268 patients, the role of ultrasound-guided transthoracic fine needle aspiration for cytological diagnosis of peripheral lung lesions. Nodule sizes ranged from 1 to 10 cm. RESULTS: From 268 patients, we obtained 174 positive specimens for malignancy, of which 155 were positive for primary lung tumors and 19 for metastasis; 76 negative; 9 inadequate; and 9 aspecific. One patient developed pneumothorax after needle aspiration and one patient emophtoe. The nodule size did not affect complication rate and diagnostic outcome. CONCLUSION: This diagnostic procedure appears to be effective, safe and feasible, even in bedridden patients. The cost is low (70Euro), the examination is fast (5-6 minutes) and well-tolerated and, if the specimen is inadequate or non-specific, it is possible to repeat the examination. Ultrasound-guided aspiration biopsy can replace the TC-guided biopsy in patients with peripheral lung nodules.