Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential.

Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of tumor cells to metastasize is dependent upon the characteristics of the tumor cells, and the conditioning of distant tissues that support colonization by metastatic cells. In this report, we investigated the systemic alterations in distant tissues caused by multiple human breast cancer cell lines and the impact of these alterations on the tumor cell phenotype. We observed that the niche within the lung, a common metastatic site, was significantly altered by MDA-MB-231, MCF7, and T47 tumors, and that the lung microenvironment stimulated, to differing extents, an epithelial-to-mesenchymal transition (EMT), reducing proliferation, increasing transendothelial migration and senescence, with no significant impact on cell death. We also investigated the ability of an implantable scaffold, which supports the formation of a distant tissue, to serve as a surrogate for the lung to identify systemic alterations. The scaffolds are conditioned by the primary tumor similarly to the lung for each tumor type, evidenced by promoting a pro-EMT profile. Collectively, we demonstrate that metastatic and non-metastatic breast cancers condition distant tissues, with distinct effects on tumor cell responses, and that a surrogate tissue can distinguish the metastatic potential of human breast cancer cell lines in an accessible site that avoids biopsy of a vital organ.

Glioblastoma multiforme influence on the elemental homeostasis of the distant organs: the results of inter-comparison study carried out with TXRF method.

Glioblastoma (GBM) is a fast-growing and aggressive brain tumor which invades the nearby brain tissue but generally does not spread to the distant organs. Nonetheless, if untreated, GBM can result in patient death in time even less than few months from the diagnosis. The influence of the tumor progress on organs other than brain is obvious but still not well described. Therefore, we examined the elemental abnormalities appearing in selected body organs (kidney, heart, spleen, lung) in two rat models of GBM. The animals used for the study were subjected to the implantation of human GBM cell lines (U87MG and T98G) characterized by different levels of invasiveness. The elemental analysis of digested organ samples was carried out using the total reflection X-ray fluorescence (TXRF) method, independently, in three European laboratories utilizing various commercially available TXRF spectrometers. The comparison of the data obtained for animals subjected to T98G and U87MG cells implantation showed a number of elemental anomalies in the examined organs. What is more, the abnormalities were found for rats even if neoplastic tumor did not develop in their brains. The most of alterations for both experimental groups were noted in the spleen and lungs, with the direction of the found element changes in these organs being the opposite. The observed disorders of element homeostasis may result from many processes occurring in the animal body as a result of implantation of cancer cells or the development of GBM, including inflammation, anemia of chronic disease or changes in iron metabolism. Tumor induced changes in organ elemental composition detected in cooperating laboratories were usually in a good agreement. In case of elements with higher atomic numbers (Fe, Cu, Zn and Se), 88% of the results were classified as fully compliant. Some discrepancies between the laboratories were found for lighter elements (P, S, K and Ca). However, also in this case, the obtained results fulfilled the requirements of full (the results from three laboratories were in agreement) or partial agreement (the results from two laboratories were in agreement).

Endovascular Embolization for Epistaxis: A Single Center Experience and Meta-Analysis.

The optimal treatment for intractable epistaxis is still controversial. Various studies have demonstrated high success rates and low complication rates for endovascular embolization. Herein, the authors report an institutional experience and meta-analysis in terms of efficacy and safety of endovascular embolization of intractable epistaxis. This was a retrospective observational study of 35 patients with epistaxis who underwent 40 embolization procedures between 2010 and 2023. The primary outcome was immediate success defined by immediate cessation of epistaxis at the end of the procedure. Immediate success was achieved in most of the procedures (39, 97.5%). During follow-up, three (7.5%) patients experienced a rebleed. Forty-one studies from 3595 articles were identified for inclusion in the meta-analysis and comprised 1632 patients. The mean pooled age was 57.5 years (95% CI: 57.2-57.8) and most patients were males (mean: 70.4, 95% CI: 69.8-71.0). Immediate success was achieved at a pooled mean of 90.9% (95% CI: 90.4-91.4) and rebleeding was observed at a pooled mean of 17% (95% CI: 16.5-17.5). In conclusion, endovascular embolization proved to be both safe and effective in treating intractable epistaxis carrying a low risk of post-operative stroke.

Gradual Changes of the Protective Effect of Phenols in Virgin Olive Oils Subjected to Storage and Controlled Stress by Mesh Cell Incubation.

The oxidation reactions that take place in virgin olive oil under moderate conditions involved the combined effect of antioxidant and prooxidant compounds. Given the complexity of oxidation processes of multicomponent matrices, there is still a need to develop new methods with a dynamic approach to study the persistence of the compounds with healthy properties. This work studied the joint evolution of them, including phenols and pheophytin a, modeling their tendency during a real storage. The regression equations performed with the total phenol concentration showed that around 2% of the concentration was lost every month. Simultaneously, the progress of oxidation was evaluated by mesh cell incubation and Fourier transform infrared analysis. This method pointed out that, in the presence of light, the prooxidant effect of pigments was able to mask the protective effect of phenols, until the pheophytin a concentration was lower than 1 mg/kg. The antioxidant effect of phenols was less remarkable when the concentration loss was 35% or more.

A synthetic metastatic niche reveals antitumor neutrophils drive breast cancer metastatic dormancy in the lungs.

Biomaterial scaffolds mimicking the environment in metastatic organs can deconstruct complex signals and facilitate the study of cancer progression and metastasis. Here we report that a subcutaneous scaffold implant in mouse models of metastatic breast cancer in female mice recruits lung-tropic circulating tumor cells yet suppresses their growth through potent in situ antitumor immunity. In contrast, the lung, the endogenous metastatic organ for these models, develops lethal metastases in aggressive breast cancer, with less aggressive tumor models developing dormant lungs suppressing tumor growth. Our study reveals multifaceted roles of neutrophils in regulating metastasis. Breast cancer-educated neutrophils infiltrate the scaffold implants and lungs, secreting the same signal to attract lung-tropic circulating tumor cells. Second, antitumor and pro-tumor neutrophils are selectively recruited to the dormant scaffolds and lungs, respectively, responding to distinct groups of chemoattractants to establish activated or suppressive immune environments that direct different fates of cancer cells.

The tomato calcium-permeable channel 4.1 (SlOSCA4.1) is a susceptibility factor for pepino mosaic virus.

The hyperosmolality-gated calcium permeable channel 4.1 (OSCA4.1) belongs to an evolutionarily conserved small family of mechano-sensitive channels. OSCA members may represent key players in plant resistance to drought and to pathogen infection but are scarcely studied. After screening for resistance to pepino mosaic virus (PepMV) a collection of 1000 mutagenized tomato families, we identified a mutant showing no symptoms and reduced virus accumulation. Resistance was mapped to chromosome 2 between positions 46 309 531 to 47 044 163, where a missense mutation caused the putative truncation of the OSCA4.1 protein. A CRISPR/Cas9 slosca4.1 mutant was resistant to PepMV, but not to tobacco mosaic virus or potato virus X. Inoculation of mutant and wild type tomato protoplasts showed that resistance was expressed in single cells, suggesting a role for SlOSCA4.1 in early viral function(s); congruently, SlOSCA4.1 re-localized to structures reminiscent of viral replication complexes. We propose that SlOSCA4.1 contributes to the correct regulation of the Ca2+ homeostasis necessary for optimal PepMV infection. PepMV is a pandemic virus that causes significant losses in tomato crops worldwide. In spite of its importance, no tomato-resistant varieties have been deployed yet; the mutant identified here has great potential to breed tomato varieties resistant to PepMV.

Effect of Flavorization on Virgin Olive Oil Oxidation and Volatile Profile.

The volatile compounds of virgin olive oil (VOO) have an important role from a sensory point of view as they are responsible for the aroma of the oil. Once the oil is obtained, auto-oxidation is the main process contributing to its deterioration, modifying the volatiles profile and aroma. The addition of aromatic herbs to VOO is a traditional technique to change the flavor and to preserve the oil. The aim of this study was to evaluate the effect on the volatile profile and sensory properties of flavoring VOO with rosemary and basil herbs and its impact on the evolution of the oxidative process during a six-month shelf-life study at 15.7 ± 3.6 °C and exposed to 500 ± 100 lx of light for 12 h each day. The determination of quality parameters, volatiles concentrations and VOO sensory properties and their comparison with the flavored VOO samples showed that the addition of basil or rosemary herbs, in addition to retarding the oxidation of the oil, allowed the discrimination of the flavored samples due to the migration of compounds from herbs to the oil. The aroma of basil olive oil (BOO) samples was mainly due to ß-pinene, ocimene and 1,8-cineol compounds while for rosemary olive oil (ROO) samples, their aroma was mainly due to the concentrations of camphene, ß-myrcene, α-terpinolene, limonene and 1,8-cineol. From the antioxidant standpoint, the effect of the herbs was more noticeable from the third month onwards.

Safety of Adenosine for the Treatment of Supraventricular Tachycardia in Hospitalized Patients with COVID-19 Pneumonia.

Coronavirus disease 2019 (COVID-19) is associated with pulmonary involvement and cardiac arrhythmias, including supraventricular tachycardia (SVT). Adenosine is commonly used to treat SVT and is generally safe, but is rarely associated with bronchospasm. There are no data regarding the safety of adenosine use in patients with COVID-19 pneumonia and physicians may hesitate to use it in such patients. We surveyed resident physicians and cardiology attendings regarding their level of comfort in administering adenosine to hospitalized COVID-19 patients. We compared a study group of 42 COVID-19 hospitalized patients who received adenosine for SVT to a matched (for age, sex, and co-morbidities) control group of 42 non-COVID-19 hospitalized patients during the same period, all of whom received IV adenosine for SVT. Escalation of care following intravenous adenosine administration was defined as increased/new pressor requirement, need for higher O2 flow rates, need for endotracheal intubation, new nebulizer therapy, or transfer to intensive care unit within 2 h of adenosine administration. Survey results showed that 82% (59/72) of residents and 62% (16/26) of cardiologists expressed hesitation/significant concerns regarding administering adenosine in hospitalized COVID-19 patients. Adenosine use was associated with escalation of care in 47.6% (20/42) COVID-19 as compared to 50% (21/42) non-COVID-19 patients (odds ratio 0.95, 95% CI 0.45-2.01, p = NS). Escalation of care was more likely in patients who were on higher FiO2, on prior nebulizer therapy, required supplemental oxygen, or were already on a ventilator. In conclusion, we identified significant hesitation among physicians regarding the use of adenosine for SVT in hospitalized COVID-19 patients. In this study, there was no evidence of increased harm from administering adenosine to patients with SVT and COVID-19. This finding needs to be confirmed in larger studies. Based on the current evidence, adenosine for treatment of SVT in this setting should not be avoided. Key Points: Question: Given the known bronchospastic effects of adenosine, is the use of adenosine safe for treatment of supraventricular tachycardia in hospitalized patients with COVID-19? Findings: A survey of residents and cardiology attending identified that a majority expressed some level of apprehension in using adenosine for SVT in COVID-19 patients. In our matched cohort study, we found adenosine use to be comparably safe in COVID-19 and non-COVID-19 hospitalized patients. Meaning: Based on current evidence, adenosine for treatment of SVT in this setting should not be avoided.

Method for the analysis of volatile compounds in virgin olive oil by SPME-GC-MS or SPME-GC-FID.

During the course of the EU H2020 OLEUM project, a harmonized method was developed to quantify volatile markers of the aroma of virgin olive oil with the aim to support the work of sensory panel test to assess the quality grade. A peer validation of this method has been carried out, with good results in terms of analytical quality parameters. The method allows the quantification of volatile compounds by SPME-GC with two possible detectors, flame ionization detector and mass spectrometry, depending on the technical facilities of the labs applying this method. The method was optimized for the quantification of 18 volatile compounds that were selected as being markers responsible for positive attributes (e.g. fruity) and sensory defects (e.g. rancid and winey-vinegary). The quantification is carried out with calibration curves corrected by the internal standards. Additionally, a protocol is provided to prepare the calibration samples. This procedure enhances reproducibility between labs since one of the main sources of errors is the application of different procedures in calibration.

Membrane-coated nanoparticles for direct recognition by T cells.

The direct modulation of T cell responses is an emerging therapeutic strategy with the potential to modulate undesired immune responses including, autoimmune disease, and allogeneic cells transplantation. We have previously demonstrated that poly(lactide-co-glycolide) particles were able to modulate T cell responses indirectly through antigen-presenting cells (APCs). In this report, we investigated the design of nanoparticles that can directly interact and modulate T cells by coating the membranes from APCs onto nanoparticles to form membrane-coated nanoparticles (MCNPs). Proteins within the membranes of the APCs, such as Major Histocompatibility Complex class II and co-stimulatory factors, were effectively transferred to the MCNP. Using alloreactive T cell models, MCNP derived from allogeneic dendritic cells were able to stimulate proliferation, which was not observed with membranes from syngeneic dendritic cells and influenced cytokine secretion. Furthermore, we investigated the engineering of the membranes either on the dendritic cells or postfabrication of MCNP. Engineered membranes could be to promote antigen-specific responses, to differentially activate T cells, or to directly induce apoptosis. Collectively, MCNPs represent a tunable platform that can directly interact with and modulate T cell responses.

Contribution of specific volatile markers to green and ripe fruity attributes in extra virgin olive oils studied with three analytical methods.

An objective sensory evaluation of extra virgin olive oil (EVOO), involving the chemical characterization of positive attributes, is of interest. These attributes are objectively divided, according to fruitiness, into "green" and "ripe" fruity. This work studied the differentiation in the volatile profile of EVOOs into these two classes, obtained by three analytical methods, including different extraction techniques and detectors and two data processing strategies, and their relation with sensory results. According to the results, each method allowed the characterization of the two classes, providing information on different volatile compounds, which increased in number through PARADISe software (14 more than the conventional processing). Moreover, some volatile compounds showed significant differences between the two classes, 16 highlighted by the variables with importance in projection (VIP) for green fruity (e.g. (Z)-3-hexen-1-ol, methyl ether) and 23 for ripe fruity EVOOs (e.g. (Z)-2-hexen-1-ol), which could be considered as useful markers to complement quality assessment.

Access Site Complications and Management of the Transradial Approach for Neurointerventions.

BACKGROUND: The transradial approach has increasingly been used for neurointerventions because of the improved safety profile compared with transfemoral. However, it is important to be aware of potential complications such as radial artery (RA) spasm, RA occlusion, pseudoaneurysm, extravasation, arteriovenous fistula, and wrist hematoma as well as their management. OBJECTIVE: To present our institution's experience with the prevention and management of local access site complications associated with the transradial approach for neuroendovascular interventions. METHODS: We conducted a retrospective analysis of a prospectively maintained database and identified 1524 consecutive neuroendovascular procedures performed using transradial access from April 2018 to February 2021. RESULTS: Among 1524 procedures, local transradial complications occurred in 1.7%. Major complications occurred at a rate of 1.2% including RA extravasation (0.3%), delayed RA occlusion (0.6%), pseudoaneurysm (0.1%), compartment syndrome (0.1%), infection (0.1%), and avulsion of the RA in 0.1% (1 of 1524) with no serious clinical consequence. Although RA occlusion is included in major complications, all cases were asymptomatic and did not require any intervention. Minor complications occurred at a rate of 0.5% including severe RA spasm (0.3%) and hematoma (0.3%). No patient in the cohort died or suffered from permanent disability from a complication related to the transradial approach. CONCLUSION: Transradial access for neurointervention has a low rate of local complications, particularly when taking appropriate prevention measures. Appropriate management of complications can prevent procedural failure and has low morbidity rates demonstrating the overall safety profile of transradial access even when complications occur.

Guselkumab effectiveness, and posology in patients with moderate to severe hidradenitis suppurativa: A retrospective bicentric experience.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recalcitrant skin disease of the terminal hair follicle. Therapeutic alternatives in HS are limited nowadays. Adalimumab, is the only approved biological treatment for patients with moderate to severe HS, and some patients do not reach an optimal response, or experience a progressive response loss, needing therapeutic alternatives. IL-23 pathway is also involved in HS pathogenesis, so its blockade could contribute to reach disease control. Guselkumab is a monoclonal antibody targeting the p19 subunit of extracellular IL-23, currently approved for psoriasis in adults, and recently some authors have reported its effectiveness in patients with moderate to severe HS refractory to other systemic treatments, becoming a hope for some patients. However adequate dosing and intervals have not been determined yet, so in most published series, doses approved for psoriasis are commonly used. On this topic a retrospective bicentric study including HS patients treated with guselkumab in the dermatologic departments of university hospitals Puerta de Hierro of Majadahonda (Madrid, Spain) and Doctor Peset of Valencia (Valencia, Spain) was conducted. We reported effectiveness, dosage and frequency of administration in the cohort, in order to establish the most effective dosage regimen and to clarify the potential role of guselkumab for this disease.

An International Survey on Olive Oils Quality and Traceability: Opinions from the Involved Actors.

A survey was launched to understand the current problems and sensitivities of the olive oil market through a series of questions clustered around topics related to quality, traceability, regulation, standard methods and other issues. The questions were selected after a series of interviews with different actors to identify those aspects where some disagreement or different points of view may exist. These questions were grouped in topics such as geographical traceability, consumer perception and quality management. The survey was addressed to eight different olive oil actors independently: producers, retailers, importers, exporters, analysts, workers at regulatory bodies, and consumers. Approximately half of the respondents (67.0% for consumers and 56.0% for the rest of olive oil actors) claimed to understand the importance of the protected designation of origin. In fact, the traceability objectives that were selected as the most relevant were those related with geographical traceability (19.3%) followed by the detection of adulteration (15.6%). Most of the respondents (80%) would agree to share data for a common database; however, some concerns exist about the use of these data and the issue of paying to have access to this database. The respondents mostly expressed an affirmative answer concerning the efficiency of panel test (74%) and a negative answer (90%) concerning the proposal of removing from regulation, although 42% agree with their revision for improvement. The opinions on "best before" date and their relationship with quality and the willingness to apply non-targeted methods were also surveyed.

Factors influencing height gain in children born small for gestational age treated with recombinant growth hormone: what extent is puberty involved?

Objective: The objective was to analyze the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) without catch-up growth treated before the onset of puberty, with follow-up until adult height. The influence of demographic and auxological factors on the final response evaluated as adult height and height gain was assessed. Patients and methods: A prospective longitudinal observational study performed in a tertiary hospital, involving SGA patients, who started treatment with rhGH between October 2003 and April 2015. Potential response predictors were evaluated by multiple regression analysis and receiver operating characteristic curves. Results: Of the initial 96 patients included, 61 patients (28 boys and 33 girls) reached adult height. Adult height gain in standard deviation (SDS) was 0.99 (0.8) and 1.49 (0.94), respectively (p < 0.05). An adult height greater than -2 SDS was reached in 75% of the girls but only in 53% of the boys. The pubertal height gain was 22.6 (5.8) cm in boys and 18.8 (4.5) cm in girls. The multiple regression model obtained for total height gain explained 42% of the variability in this variable including sex, height gain during the first year, and the difference from target height at the start of treatment. A first-year height gain of 0.69 SDS was the optimal point for assessing a final height gain greater than 1.5 SDS with a specificity of 70% and a sensitivity of 71%. Conclusion: Most SGA patients achieve normalization of height above -2 SD, the percentage being higher in girls. According to our predictive model, height gain in the first year is the most important variable for predicting good response to treatment. During puberty, there is a loss of height SDS, probably due to a lower total pubertal gain with respect to the reference population, which is more marked in boys.

Retreatment Strategies in Aneurysm Woven Endobridge Recurrences: A Case Series.

BACKGROUND: The treatment of wide-necked and bifurcation aneurysms has become a common indication for the Woven Endobridge (WEB) device. In many instances, WEB embolization fails and retreatment strategies for the recanalized aneurysms have not been established and may be challenging. OBJECTIVE: To report an experience with retreatment strategies after WEB failure in 7 cases involving various aneurysm shapes, sizes, and location using multiple strategies including endovascular modalities and microsurgical clip ligation. METHODS: Data were retrospectively collected from 1 high-volume cerebrovascular center for 7 patients treated with a WEB device for an aneurysm who subsequently required retreatment for that same aneurysm from 2015 through January 2021. RESULTS: We identified 7 patients with WEB recurrences over a period of 6 years. Four patients initially presented with incidental findings, whereas 3 patients presented with subarachnoid hemorrhage. One patient was lost to follow-up and presented with a rerupture, whereas the 6 other patients were diagnosed with routine follow-up. Two patients received clip ligation, 2 had simple coil embolization, 1 had stent-assisted coil embolization, 1 had a flow-diverting stent, and 1 patient required 2 retreatments; he received stent-assisted coil embolization for the first retreatment and a simple coil embolization for the second retreatment. All patients had excellent angiographic outcomes and no complications. CONCLUSION: The authors conclude that aneurysm recurrence after WEB is very diverse, and no single modality can properly address all recurrences. Rather, an individualized approach based on aneurysm features, neurointerventionalist expertise, and patient preference should be implemented.