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The article presents an interview with Laurence Monnais, a professor of public health history at the University of Lausanne and the Centre Hospitalier Universitaire Vaudois. Topics include her transition from colonial studies to health history, her fieldwork experience in Southeast Asia and its impact on her research, and her evolving approach to postcolonial and decolonial research frameworks in public health.

Background: An array of evidence shows how the presence of implicit bias in clinical encounters can negatively impact provider-patient communication, quality of care and ultimately contribute to health inequities. Reflexive practice has been explored as an approach to identify and address implicit bias in healthcare providers, including medical students. At the Lausanne School of Medicine, a clinically integrated module was introduced in 2019 to raise students' awareness of gender bias in medical practice using a reflexivity and positionality approach. The purpose of this study is to describe the gender bias that were identified by medical students, analysing their types, places and modes of emergence during a clinical encounter. It further explores how positionality supported students' reflection on the way in which social position modulates their relationship to patients. Methods: As part of the teaching activity, medical students individually reflected on gender bias in a specific clinical encounter by answering questions in their electronic portfolio. The questionnaire included a section on positionality. We qualitatively analysed the students' assignments (n=76), applying a thematic analysis framework. Results: Medical students identified and described gender biases occurring at different moments of the clinical encounter (anamnesis (i.e. patient history), physical exam, differential diagnosis, final management). They causally associated these biases with wider social phenomena such as the gendered division of labour or stereotypes around sexuality and gender. Analysing students' reflections on how their position influenced their relationship with patients, we found that the suggested exercise revealed a major contradiction in the process of medical enculturation: the injunction to be neutral and objective erases the social and cultural context of patients and impedes an understanding of gender bias. Conclusion: Gender biases are present in the different steps of a clinical consultation and are rooted in broader gendered social representations. We further conclude that the tension between a quest for objectivity and the reality of social encounters should be made explicit to students, because it is constitutive of medical practice. [ABSTRACT FROM AUTHOR]

Monkeypox virus (MPXV) is a zoonotic disease endemic in the rainforest countries of Central and West Africa. Understanding the immune response in zoonosis is fundamental to prevent and contrast viral spreading. MPXV is a close relative of Variola (smallpox) virus and vaccination with vaccinia virus gives approximatively 85% of protection against MPXV. With the emergence of the recent MPXV outbreak, JYNNEOS vaccine has been proposed to individuals at high‐risk of exposure. Comparative data on MPXV immune response in vaccinated or infected subjects are still limited. Here we set‐up an immunofluorescence method for the evaluation of humoral response elicited by natural infection and healthy vaccinated subjects, including historically smallpox‐vaccinated individuals and newly vaccinated subjects. Neutralization assay was also included, and in vaccinated subjects, cell‐mediated response was evaluated. We observed that the natural infection produces a strong immune response that can control the disease. In naïve subjects, a second dose boosts the serological response to levels similar to those of the MPXV patients. Last, smallpox‐vaccinated controls retain a degree of protection, even after years from vaccination, most visible in the t‐cellular response. [ABSTRACT FROM AUTHOR]

The role and durability of the immunogenicity of the BNT162b2 mRNA vaccine against severe acute respiratory virus 2 (SARS-CoV-2), in cancer patients one year after receiving the third dose have to be elucidated. We have prospectively evaluated the long-term immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in 55 patients undergoing active treatment. Neutralizing antibody (NT Ab) titers against Omicron variants and total anti-trimeric S IgG levels were measured one year after the third dose. Heparinized whole-blood samples were used for the assessment of the SARS-CoV-2 interferon-γ release assay (IGRA). Thirty-seven patients (67.3%) showed positive total anti-trimeric S IgG one year after the third dose. Looking at the T-cell response against the spike protein, the frequency of responder patients did not decrease significantly between six and twelve months after the third dose. Finally, less than 20% of cancer patients showed an undetectable NT Ab titer against BA.1 and BA.5 variants of concern (VOCs). Underlying therapies seem to not affect the magnitude or frequency of the immune response. Our work underlines the persistence of humoral and cellular immune responses against BNT162b2 in a cohort of cancer patients one year after receiving the third dose, regardless of the type of underlying therapy. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) infection represents a major complication for solid organ transplant recipients. The aim of this study was to verify if the measurement of HCMV‐specific T‐cells could help to identify patients protected against HCMV disease cytokine flow cytometry using infected dendritic cells as stimulus (CFC‐iDC, which discriminates between CD4+ and CD8+ T cells), and ELISPOT, using infected cell lysate (ELISPOT‐iCL) or pp65 (ELISPOT‐pp65) as stimulus, were adopted. Among the 47 kidney transplant recipients (KTR) enrolled, 29 had a self‐resolving HCMV infection (Controllers) and 18 required antiviral treatment (Non‐Controllers). HCMV‐specific T‐cell frequency at the peak of HCMV infection identified Controllers and Non‐Controllers, although the diagnostic performance of CD8+ CFC‐iDC (area under the curve [AUC] of the receiver‐operator characteristic curve: 0.65) was lower than that of CD4+ CFC‐iDC (AUC: 0.83), ELISPOT‐iCL (AUC: 0.83) and ELISPOT‐pp65 (AUC: 0.80). CFC‐iDC detected a protective immune reconstitution significantly earlier (median time: 38 days) than ELISPOT‐iCL and ELISPOT‐pp65 (median time: 126 and 133 days, respectively). Time to protective immune reconstitution in Non‐Controllers was significantly longer than in Controllers with the ELISPOT and the CD4+ CFC‐iDC assays, but not with CD8+ CFC‐iDC. The majority of patients did not require antiviral treatment after protective immune reconstitution, with the exception of five patients according to CFC‐iDC assay, one patient according to ELISPOT‐iCL assay and three patients according to ELISPOT‐pp65 assay. Monitoring the HCMV‐specific immunological reconstitution with is effective in discriminating KTR at risk of or protected from HCMV disease and the ELISPOT assays are suitable for implementation in the clinical setting. [ABSTRACT FROM AUTHOR]

We reported the long-term kinetics of immune response after vaccination and evaluated the immunogenicity after a third dose of mRNA vaccine in 86 healthcare workers. Humoral response was analyzed by measuring anti-spike IgG and SARS-CoV-2 NTAbs titer; cell-mediated response was measured as frequency of IFN-γ producing T-cells and cell proliferation. Memory B cells secreting SARS-CoV-2 RBD-IgG were measured by B-spot assay. At three weeks after the third dose (T4), the frequency of subjects showing NT-Abs titer at the upper detection limit (≥640) was significantly higher than that observed at three weeks after the second dose (26/77; 33.7% vs. 9/77; 11.6%; p = 0.0018). Additionally, at T4, all the subjects reached positive levels of T-cell mediated response (median 110 SFU/106 PBMC, IQR 73-231). While the number of IFNγ-producing T-cells decreased between second and third dose administration, the T-cell proliferative response did not decrease but was sustained during the follow-up. Among T-cell subsets, a higher proliferative response was observed in CD4+ than in CD8+ population. Moreover, even if a decline in antibody response was observed between the second and third dose, a sustained persistence of memory B cells was observed. Subsequently, the third dose did not affect the frequency of memory B cells, while it restored or increased the peak antibody levels detected after the second dose. [ABSTRACT FROM AUTHOR]

Purpose: This work aims to investigate the supramolecular binding interactions that occur between iodinated X‐ray contrast agents (CAs) and macrocyclic gadolinium (Gd)–based MRI contrast agents (GBCAs). This study provides some new insights in the renal excretion pathways of the two types of imaging probes. Methods: The water‐proton relaxivities (r1) of clinically approved macrocyclic and linear GBCAs have been measured in the presence of different iodinated X‐ray contrast agents at different magnetic field strengths in buffer and in serum. The in vivo MRI and X‐ray CT of mice injected with either Gd‐HPDO3A or a Gd‐HPDO3A + iodixanol mixture were then acquired to assess the biodistribution of the two probes. Results: A significant increase in r1 (up to approximately 200%) was observed for macrocyclic GBCAs when measured in the presence of an excess of iodinated X‐ray CAs (1:100 mol:mol) in serum. The co‐administration of Gd‐HPDO3A and iodixanol in vivo resulted in a marked increase in the signal intensity of the kidney regions in T1‐weighted MR images. Moreover, the co‐presence of the two agents resulted in the extended persistence of the MRI signal enhancement, suggesting that the Gd‐HPDO3A/iodixanol adduct was eliminated more slowly than the typical washing out of Gd‐HPDO3A. Conclusions: The reported results show that it is possible to detect the co‐presence of iodinated agents and macrocyclic GBCAs in contrast‐enhanced MR images. The new information may be useful in the design of novel experiments toward improved diagnostic outcomes. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely impacted on public health, mainly on immunosuppressed patients, including solid organ transplant recipients. Vaccination represents a valuable tool for the prevention of severe SARS-CoV-2 infection, and the immunogenicity of mRNA vaccines has been evaluated in transplanted patients. In this study, we investigated the role of a third dose of the BNT162b2 vaccine in a cohort of kidney transplant recipients, analyzing both humoral and cell-mediated responses. We observed an increased immune response after the third dose of the vaccine, especially in terms of Spike-specific T cell response. The level of seroconversion remained lower than 50% even after the administration of the third dose. Mycophenolate treatment, steroid administration and age seemed to be associated with a poor immune response. In our cohort, 11/45 patients experienced a SARS-CoV-2 infection after the third vaccine dose. HLA antibodies appearance was recorded in 7 out 45 (15.5%) patients, but none of the patients developed acute renal rejection. Further studies for the evaluation of long-term immune responses are still ongoing, and the impact of a fourth dose of the vaccine will be evaluated. [ABSTRACT FROM AUTHOR]

Since the identification of the new severe acute respiratory syndrome virus 2 (SARS-CoV-2), a huge effort in terms of diagnostic strategies has been deployed. To date, serological assays represent a valuable tool for the identification of recovered COVID-19 patients and for the monitoring of immune response elicited by vaccination. However, the role of T-cell response should be better clarified and simple and easy to perform assays should be routinely introduced. The main aim of this study was to compare a home-made assay for whole blood stimulation with a standardized ELISpot assay design in our laboratory for the assessment of spike-specific T-cell response in vaccinated subjects. Even if a good correlation between the assays was reported, a higher percentage of responder subjects was reported for immunocompromised subjects with ELISpot assay (56%) than home-made whole blood stimulation assay (33%). Additionally, three commercial assays were compared with our home-made assay, reporting a good agreement in terms of both positive and negative results. [ABSTRACT FROM AUTHOR]

D‐Glucose and 3‐O‐Methyl‐D‐glucose (3OMG) have been shown to provide contrast in magnetic resonance imaging‐chemical exchange saturation transfer (MRI‐CEST) images. However, a systematic comparison between these two molecules has yet to be performed. The current study deals with the assessment of the effect of pH, saturation power level (B1) and magnetic field strength (B0) on the MRI‐CEST contrast with the aim of comparing the in vivo CEST contrast detectability of these two agents in the glucoCEST procedure. Phosphate‐buffered solutions of D‐Glucose or 3OMG (20 mM) were prepared at different pH values and Z‐spectra were acquired at several B1 levels at 37°C. In vivo glucoCEST images were obtained at 3 and 7 T over a period of 30 min after injection of D‐Glucose or 3OMG (at doses of 1.5 or 3 g/kg) in a murine melanoma tumor model (n = 3–5 mice for each molecule, dose and B0 field). A markedly different pH dependence of CEST response was observed in vitro for D‐Glucose and 3OMG. The glucoCEST contrast enhancement in the tumor region following intravenous administration (at the 3 g/kg dose) was comparable for both molecules: 1%–2% at 3 T and 2%–3% at 7 T. The percentage change in saturation transfer that resulted was almost constant for 3OMG over the 30‐min period, whereas a significant increase was detected for D‐Glucose. Our results show similar CEST contrast efficiency but different temporal kinetics for the metabolizable and the nonmetabolizable glucose derivatives in a tumor murine model when administered at the same doses. [ABSTRACT FROM AUTHOR]

A novel, highly biocompatible, well soluble melanin-based probe obtained from the conjugation of melanin macromolecule to bovine serum albumin (BSA) was tested as a contrast agent for photoacoustic tumor imaging. Five soluble conjugates (PheoBSA A-E) were synthesized by oxidation of dopamine (DA) in the presence of variable amounts of BSA. All systems showed the similar size and absorbance spectra, being PheoBSA D (DA:BSA ratio 1:2) the one showing the highest photoacoustic efficiency. This system was then selected for the investigations as it showed a marked enhancement of the photoacoustic (PA) contrast in the tumor region upon iv injection. Biodistribution studies confirmed the accumulation of PheoBSA D within the tumor region and showed fast renal elimination, lack of cell toxicity, and good hemocompatibility. A higher PA contrast enhancement was observed in the case of PC3 prostate tumor xenograft when compared to the TS/A breast one, likely reflecting different vascularization/extravasation properties between the two tumor murine models. The improved PA properties shown by PheoBSA D allowed to set up a 3D dynamic contrast-enhanced (DCE) approach that demonstrated a persistent increase of the PA signal in the tumor region for a long period. Overall, the herein reported results demonstrate that PheoBSA D is a promising blood pool contrast agent for in vivo PA imaging, particularly useful for the set-up of 3D DCE-PA approaches to monitor tumor vascular properties. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PCa), the most widespread male cancer in western countries, is generally eradicated by surgery, especially if localized. However, during surgical procedures, it is not always possible to identify malignant tissues by visual inspection. Among the possible consequences, there is the formation of positive surgical margins, often associated with recurrence. In this work, the gastrin-releasing peptide receptor (GRPR), overexpressed in the prostatic carcinoma and not in healthy tissues or in benign hyperplasia (BPH), is proposed as target molecule to design a novel near-infrared fluorescent (NIRF) probe for image-guided prostatectomy.Procedures: The NIRF dye Sulfo-Cy5.5 was conjugated to a Bombesin-like peptide (BBN), targeting GRPR. The final product, called BBN-Cy5.5, was characterized and tested in vitro on PC-3, DU145, and LnCAP cell lines, using unconjugated Sulfo-Cy5.5 as control. In vivo biodistribution studies were performed by optical imaging in PC-3 tumor-bearing and healthy mice. Finally, simulation of the surgical protocol was carried out.Results: BBN-Cy5.5 showed high water solubility and a good relative quantum yield. The ability of the probe to recognize the GRPR, highly expressed in PC-3 cells, was tested both in vitro and in vivo, where a significant tumor accumulation was achieved 24 h post-injection. Furthermore, a distinguishable fluorescent signal was visible in mice bearing PCa, when the surgery was simulated. By contrast, low signal was found in healthy or BPH-affected mice.Conclusions: This work proposes a new NIRF probe ideal to target GRPR, biomarker of PCa. The promising data obtained suggest that the dye could allow the real-time intraoperative visualization of prostate cancer. [ABSTRACT FROM AUTHOR]

Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic products, resulting in enhanced acidification of the extracellular pH (pHe ~ 6.5), which is a salient feature of the tumor microenvironment. Despite the importance of pH and tumor acidosis, there is currently no established clinical tool available to image the spatial distribution of tumor pHe. The purpose of this review is to describe various imaging modalities for measuring intracellular and extracellular tumor pH. For each technique, we will discuss main advantages and limitations, pH accuracy and sensitivity of the applied pH-responsive probes and potential translatability to the clinic. Particular attention is devoted to methods that can provide pH measurements at high spatial resolution useful to address the task of tumor heterogeneity and to studies that explored tumor pH imaging for assessing treatment response to anticancer therapies. [ABSTRACT FROM AUTHOR]

Purpose: The discussed topic about gadolinium-based contrast agents (GBCA) safety has recently been revived due to the evidence of hyperintensities observed in the dentate nucleus (DN) and globus pallidus (GP) in the brain of patients with normal kidney function. Several preclinical studies have been conducted to understanding how the use of GBCAs can promote the gadolinium deposition in the brain. Here, we evaluate the impact of chronic cerebral hypoperfusion on gadolinium presence.Methods: T1 hyperintensities and BBB integrity were evaluated by MRI in chronically hypoperfused and healthy rats injected with either gadodiamide or hypertonic saline. Additionally, the assessment of glucose metabolism by PET imaging and the gadolinium content by ICP-MS was performed after the last MR scan.Results: Chronically hypoperfused rats displayed a greater MRI T1w signal in the DCN and hippocampus compared to Sham-operated animals, suggesting gadolinium accumulation. Dynamic contrast-enhanced (DCE) MRI assessment of BBB permeability revealed loss of integrity (high Ktrans) after rat injury in the dentate nuclei and hippocampus. Ex vivo tissue analysis showed greater gadolinium retention in the cerebellum and subcortical regions, supporting the imaging finding. FDG-PET imaging of the cerebellum did not reveal abnormal uptake in the DCN after chronic cerebral hypoperfusion.Conclusion: Higher signal intensity followed by higher Gd concentration observed in DCN and hippocampus of animals subjected to cerebral injury can be associated with an increase in BBB permeability due to the applied vascular dementia animal model. Nonetheless, no glucose metabolism abnormalities were detected in chronically hypoperfused cerebellum. [ABSTRACT FROM AUTHOR]

The first one-step synthesis of dumbbell-like gold–iron oxide nanoparticles has been reported here. Surface functionalization with a biocompatible chitosan matrix allowed us to obtain a novel targetable diagnostic and therapeutic tool. [ABSTRACT FROM AUTHOR]

Peptide materials based on the aggregation of polyphenylalanine conjugates containing gadolinium complexes and acting as potential contrast agents (CAs) in magnetic resonance imaging (MRI) are described. Monomers contain two (F2) or four (F4) phenylalanine residues for self-assembly, a chelating agent, 1,4,7,10-tetraazacyclododecane-N,N,N,N-tetraacetic acid (DOTA) or diethylenetriaminepentaacetic acid (DTPA), for achieving gadolinium coordination, and ethoxylic linkers at two (L2) or six (L6) poly(ethylene glycol) (PEG) units between the chelating group and the peptide region. Both DOTA and DTPA tetraphenylalanine derivatives, and their gadolinium complexes DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4, are able to self-aggregate at very low concentration. Structural characterization, obtained by circular dichroism and infrared measurements, confirms the amyloid type fibril formation in which an antiparallel peptide alignment is preferred. Amyloid type fibril formation is also observed, in solid state, by transmission electron microscopy images and X-ray diffraction patterns. The relaxivity values of DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4 and their ability to enhance the MRI cellular response on the J774A.1 mouse macrophages cell line indicate that these peptide materials are promising candidate as a new class of supramolecular gadolinium based MRI contrast agents. [ABSTRACT FROM AUTHOR]

The purpose of the work was to set-up a simple method to evaluate the contribution of Mn2+ ions in the intra- and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by 'silencing' the relaxation enhancement arising from Mn2+ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10-tetraazacyclododecane-1,7-diacetic acid) towards Mn2+ ions, as the addition of Ca-DO2A to a solution of MnCl2 causes a drop of relaxivity upon the formation of the highly stable and low-relaxivity Mn-DO2A. It has been proved that the sequestering ability of DO2A towards Mn2+ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn-DO2A does not enter cell membranes, nor does the presence of Ca-DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T1-weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca-DO2A. By applying the method to B16F10 tumor bearing mice, T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP-MS measurements. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chlorotoxin-targeted polymeric nanoparticles containing entrapped gold nanorods as potential therapeutic agent for glioblastoma multiforme have been developed and evaluated. In first proof of concept experiments, in vitro specific uptake in cancer cells and selective laser-induced cell death have been shown. In vivo studies with optical imaging showed increased retention of targeted NPs in the tumor. [ABSTRACT FROM AUTHOR]

A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) bearing an adamantyl group (Gd L1) able to form strong supramolecular adducts with specific hosts such as β-cyclodextrin (β-CD), poly-β-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd L1 were investigated in aqueous solution by measuring the H relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM s, a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5-3.0 T). The noncovalent interaction of Gd L1 with β-CD, poly-β-CD, and HSA and the relaxometric properties of the resulting host-guest adducts were investigated using H relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd L1-β-CD and Gd L1-poly-β-CD, respectively. Binding of Gd L1 to HSA ( K = 1.2 × 10 M) results in a remarkable relaxivity of 41.4 mM s for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd L1-β-CD to Gd L1-HSA. Finally, the applicability of Gd L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation. [ABSTRACT FROM AUTHOR]

Gadolinium complexes linked to an apolar fragment are known to be efficiently internalized into various cell types, including hepatocytes. Two lipid-functionalized gadolinium chelates have been investigated for the targeting of the human liver fatty acid binding protein (hL-FABP) as a means of increasing the sensitivity and specificity of intracellular-directed MRI probes. hL-FABP, the most abundant cytosolic lipid binding protein in hepatocytes, displays the ability to interact with multiple ligands involved in lipid signaling and is believed to be an obligate carrier to escort lipidic drugs across the cell. The interaction modes of a fatty acid and a bile acid based gadolinium complex with hL-FABP have been characterized by relaxometric and NMR experiments in solution with close-to-physiological protein concentrations. We have introduced the analysis of paramagnetic-induced protein NMR signal intensity changes as a quantitative tool for the determination of binding stoichiometry and of precise metal-ion-center positioning in protein-ligand supramolecular adducts. A few additional NMR-derived restraints were then sufficient to locate the ligand molecules in the protein binding sites by using a rapid data-driven docking method. Relaxometric and 13C NMR competition experiments with oleate and the gadolinium complexes revealed the formation of heterotypic adducts, which indicates that the amphiphilic compounds may co-exist in the protein cavity with physiological ligands. The differences in adduct formation between fatty acid and bile acid based complexes provide the basis for an improved molecular design of intracellular targeted probes. [ABSTRACT FROM AUTHOR]

Endocytosis is a common internalization pathway for cellular labeling with MRI contrast agents. However, the entrapment of the Gd(III) complexes into endosomes results in a 'quenching' of the attainable relaxivity when the number of Gd(III) complexes reaches the number of ca. 1 × 109/cell. Herein we show that the use of the newly developed photochemical internalization technique provides an efficient method for attaining the endosomal escape of GdHPDO3A molecules entrapped by pinocytosis into different kind of cells. Furthermore, it has been found that a new 'quenching' limit is observed when the number of Gd-HPDO3A complexes is ca. five times higher than the value observed for the endosome entrapped conditions. The observed behavior is explained in terms of the attainment of the conditions in which the difference in proton relaxation rates between the cytoplasmic and the extracellular compartment is higher than the exchange rate of water molecules across the cellular membrane. The experimental data points have been reproduced by using a properly designed theoretical compartment T1-relaxation model. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The immunogenicity of severe acute respiratory syndrome 2 virus (SARS-CoV-2) vaccines in immunocompromised patients remains to be further explored. Here, we evaluated the immunogenicity elicited by complete vaccination with BNT162b2 vaccine in solid organ transplant recipients (SOTRs). A cohort of 110 SOTRs from Northern Italy were vaccinated with two doses of BNT162b2 mRNA vaccine and prospectively monitored at baseline and after 42 days. Both SARS-CoV-2 naïve and recovered subjects were included. Humoral response elicited by vaccination, including SARS-CoV-2 neutralizing antibodies (SARS-CoV-2 NT Abs), was evaluated; additionally, ex-vivo ELISpot assay was performed for the quantification of Spike-specific T-cell response. Results were compared with those obtained in a cohort of healthy subjects. In a subset of patients, humoral and T-cell responses against delta variant were also evaluated. Less than 20% of transplanted subjects developed a positive humoral and cell-mediated response after complete vaccination schedule. Overall, median levels of immune response elicited by vaccination were significantly lower with respect to controls in SARS-CoV-2 naïve transplant, but not in SARS-CoV-2 recovered transplanted patients. Additionally, a significant impairment of both humoral and cell-mediated response was observed in mycophenolate-treated patients. Positive delta-SARS-CoV-2 NT Abs levels were detected in almost all the SARS-CoV-2 recovered subjects but not in previously uninfected patients. Our study supports previous observations of a low level of seroconversion after vaccination in transplanted patients. [ABSTRACT FROM AUTHOR]

Labeling of macrophages with perfluorocarbon (PFC)-based compounds allows the visualization of inflammatory processes by 19F-magnetic resonance imaging (19F-MRI), due to the absence of endogenous background. Even if PFC-labeling of monocytes/macrophages has been largely investigated and used, information is lacking about the impact of these agents over the polarization towards one of their cell subsets and on the best way to image them. In the present work, a PFC-based nanoemulsion was developed to monitor the course of inflammation in a model of spinal cord injury (SCI), a pathology in which the understanding of immunological events is of utmost importance to select the optimal therapeutic strategies. The effects of PFC over macrophage polarization were studied in vitro, on cultured macrophages, and in vivo, in a mouse SCI model, by testing and comparing various cell tracking protocols, including single and multiple administrations, the use of MRI or Point Resolved Spectroscopy (PRESS), and application of pre-saturation of Kupffer cells. The blood half-life of nanoemulsion was also investigated by 19F Magnetic Resonance Spectroscopy (MRS). In vitro and in vivo results indicate the occurrence of a switch towards the M2 (anti-inflammatory) phenotype, suggesting a possible theranostic function of these nanoparticles. The comparative work presented here allows the reader to select the most appropriate protocol according to the research objectives (quantitative data acquisition, visual monitoring of macrophage recruitment, theranostic purpose, rapid MRI acquisition, etc.). Finally, the method developed here to determine the blood half-life of the PFC nanoemulsion can be extended to other fluorinated compounds. [ABSTRACT FROM AUTHOR]

The transplantation of mesenchymal stem cells (MSCs) holds great promise for the treatment of a plethora of human diseases, but new noninvasive procedures are needed to monitor the cell fate in vivo. Already largely used in medical diagnostics, the fluorescent dye indocyanine green (ICG) is an established dye to track limited numbers of cells by optical imaging (OI), but it can also be visualized by photoacoustic imaging (PAI), which provides a higher spatial resolution than pure near infrared fluorescence imaging (NIRF). Because of its successful use in clinical and preclinical examinations, we chose ICG as PAI cell labeling agent. Optimal incubation conditions were defined for an efficient and clinically translatable MSC labeling protocol, such that no cytotoxicity or alterations of the phenotypic profile were observed, and a consistent intracellular uptake of the molecule was achieved. Suspensions of ICG‐labeled cells were both optically and optoacoustically detected in vitro, revealing a certain variability in the photoacoustic spectra acquired by varying the excitation wavelength from 680 to 970 nm. Intramuscular engraftments of ICG‐labeled MSCs were clearly visualized by both PAI and NIRF over few days after transplantation in the hindlimb of healthy mice, suggesting that the proposed technique retains a considerable potential in the field of transplantation‐focused research and therapy. Stem cells were labeled with the Food and Drug Administration (FDA)‐approved fluorescent dye ICG, and detected by both PAI and OI, enabling to monitor the cell fate safely, in dual modality, and with good sensitivity and improved spatial resolution. [ABSTRACT FROM AUTHOR]