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Background The incidence of skin cancer has shown an increasing trend in the world and in France over the last four decades. In this context, the delay to access a specialist opinion strongly impacts the patient outcomes. However, the medical demographics of dermatologists in France have been decreasing over the past years. Hence, a tele-expertise (TLE) experiment for skin tumors detection, which allows general practitioners to obtain feedback from a dermatologist within 7 days using a smartphone application, has been set up in the Hauts-de-France region since 2015. Thus, this study aims at understanding the advantages and drawbacks of TLE in the detection of skin tumors perceived by general practitioners. Methods Exploratory study carried out with 15 general practitioners participating in the experiment in the Hauts-de-France region. Semi-structured interviews were conducted between february and april 2021 and analyzed after transcription. Results The main advantages perceived by general practitioners are: (i) fast access to a specialized feedback; (ii) formalization of the request and commitment of the dermatologist; (iii) ease of regulating patients to a specialist; (iv) lower travel frequency and stress for patients; (v) ability to send medical information securely. The drawbacks are most related to the lack of functionalities and the graphical user interface of the application. Conclusions Tele-expertise is a well accepted technological innovation in dermatology among general practitioners, which enables the best use of the scarce medical resources available in the region and to address the needs of patients. The sustainability of TLE in dermatology and its extension to other territories is possible and desirable. Key messages Tele-expertise in dermatology has its place in enabling the early management of malignant skin tumors. The qualitative approach makes it possible to understand general practitioners visions after the introduction of a technological innovation into their practices.

Highlights •This study combined ALDH activity with cell surface marker expression to develop a multiparametric flow cytometry assay to assess proangiogenic progenitor and proinflammatory cell content in the peripheral blood of patients with T2D compared with age-matched control subjects. •Patients with T2D exhibited an increased frequency of proinflammatory ALDHhi cells with granulocyte side scatter properties and a decreased frequency of circulating monocytes with an M2 phenotype that is associated with proangiogenic and anti-inflammatory functions. •Patients with T2D exhibited significant depletion of circulating provascular ALDHhiCD34+ progenitor cells with primitive, migratory, endothelial, and pericyte phenotypes. •Subgroup analyses that stratified patients with T2D according to age, duration of T2D, insulin requirement, and glycosylated hemoglobin levels revealed that only the duration of T2D correlated with vascular progenitor cell depletion. •Flow cytometric assessment of circulating ALDHhi cell subsets represents a promising translational approach for identifying patients with T2D at increased risk for cardiovascular comorbidities.

Chronic cardiometabolic assaults during type 2 diabetes (T2D) and obesity induce a progenitor cell imbalance in the circulation characterized by overproduction and release of pro-inflammatory monocytes and granulocytes from the bone marrow alongside aberrant differentiation and mobilization of pro-vascular progenitor cells that generate downstream progeny for the coordination of blood vessel repair. This imbalance can be detected in the peripheral blood of individuals with established T2D and severe obesity using multiparametric flow cytometry analyses to discern pro-inflammatory vs. pro-angiogenic progenitor cell subsets identified by high aldehyde dehydrogenase activity, a conserved progenitor cell protective function, combined with lineage-restricted cell surface marker analyses. Recent evidence suggests that progenitor cell imbalance can be reversed by treatment with pharmacological agents or surgical interventions that reduce hyperglycaemia or excess adiposity. In this state-of-the-art review, we present current strategies to assess the progression of pro-vascular regenerative cell depletion in peripheral blood samples of individuals with T2D and obesity and we summarize novel clinical data that intervention using sodium-glucose co-transporter 2 inhibition or gastric bypass surgery can efficiently restore cell-mediated vascular repair mechanisms associated with profound cardiovascular benefits in recent outcome trials. Collectively, this thesis generates a compelling argument for early intervention using current pharmacological agents to prevent or restore imbalanced circulating progenitor content and maintain vascular regenerative cell trafficking to sites of ischaemic damage. This conceptual advancement may lead to the design of novel therapeutic approaches to prevent or reverse the devastating cardiovascular comorbidities currently associated with T2D and obesity.

Chronic metabolic dysfunction as a result of type 2 diabetes (T2D) increases susceptibility to the development of ischemic cardiovascular disease (CVD) (1). The search for therapies to improve cardiovascular health in individuals afflicted with T2D has led to the discovery and utilization of a novel class of glucose-lowering drugs called sodium–glucose cotransporter 2 inhibitors (SGLT2i). Located in the proximal tubule of the kidney, the SGLT2 receptor directs the reuptake of glucose and sodium into the circulation (2,3). Inhibition of this pathway results in glucosuria/natriuresis and represents a novel metabolic mechanism to reduce hyperglycemia during T2D. Several randomized clinical trials in people with and without diabetes have now established a critical role for SGLT2i in the reduction of cardiovascular and cardiorenal events (4,5). While direct myocardial and indirect metabolic effects have been proposed to explain these benefits, recent data suggest that SGLT2 inhibition stimulates vascular repair via increased trafficking of bone marrow–derived provascular progenitor cells essential for vessel regeneration (6–9). In this issue of Diabetes , Albiero et al. (10) definitively demonstrate that despite low levels of expression of SGLT2 on hematopoietic cells, SGLT2 inhibition with dapagliflozin improved endothelial repair through enhanced recruitment of hematopoietic stem/progenitor cell (HSPC) progeny from the bone marrow (BM) to the site of vessel injury. In concept, circulating HSPC represent critical intermediates in blood vessel homeostasis via the coordination of angiogenic, arteriogenic, and vasculogenic processes (11). Seminal contributions by the Fadini group and others have previously established a significant depletion in circulating provascular HSPC during T2D, which contributes to …

Summary The examination of circulating pro-vascular progenitor cell frequency and function is integral in understanding aberrant blood vessel homeostasis in individuals with cardiometabolic disease. Here, we outline the characterization of progenitor cell subsets from peripheral blood using high aldehyde dehydrogenase (ALDH) activity, an intracellular detoxification enzyme previously associated with pro-vascular progenitor cell status. Using this protocol, cells can be examined by flow cytometry for ALDH activity and lineage restricted cell surface markers simultaneously. For complete details on the use and execution of this protocol, please refer to Terenzi et al. (2019) and Hess et al. (2019, 2020)., Graphical Abstract, Highlights • Aldehyde dehydrogenase is superior in the isolation of progenitor cells • Flow cytometry is an effective method to characterize pro-vascular cells • Aggressive gating strategies allows for in-depth progenitor cell characterization • The use of fresh blood samples will yield most accurate cell prevalence, The examination of circulating pro-vascular progenitor cell frequency and function is integral in understanding aberrant blood vessel homeostasis in individuals with cardiometabolic disease. Here, we outline the characterization of progenitor cell subsets from peripheral blood using high aldehyde dehydrogenase (ALDH) activity, an intracellular detoxification enzyme previously associated with pro-vascular progenitor cell status. Using this protocol, cells can be examined by flow cytometry for ALDH activity and lineage restricted cell surface markers simultaneously.

Summary Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and “regenerative cell exhaustion” (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects with severe obesity, suggesting the restoration of a microenvironment to support vessel homeostasis. These data suggest that bariatric surgery may reverse deleterious events that predispose patients with morbid obesity to cardiovascular risk., Graphical Abstract, Highlights Obesity features a low frequency of ALDH and CD133 co-expressing cells Bariatric surgery results in lower granulocyte precursors expressing ALDH Macrophage balance favors M2 polarization following bariatric surgery Cellular changes after bariatric surgery give insight into reducing CV risk, In Hess et al., the quantification of circulating progenitor cells in individuals with obesity, before and 3 months after bariatric surgery, demonstrates reduced granulocyte precursors and increased pro-angiogenic monocytes with M2 polarization. These alterations are consistent with improved vessel homeostasis and recovered cardiovascular health observed following bariatric surgery.

In response to the Letter by Fadini, Hess et al. discuss the interpretation of their data and the details of the multiparametric analyses employed to measure the changes in circulating provascular cell content in patients with type 2 diabetes receiving empagliflozin compared to placebo treatment.

Critical limb ischemia (CLI), the most severe form of peripheral artery disease, is characterized by pain at rest and non-healing ulcers in the lower extremities. For patients with CLI, where the extent of atherosclerotic artery occlusion is too severe for surgical bypass or percutaneous interventions, limb amputation remains the only treatment option. Thus, cell-based therapy to restore perfusion and promote wound healing in patients with CLI is under intense investigation. Despite promising preclinical studies in animal models, transplantation of bone marrow (BM)-derived cell populations in patients with CLI has shown limited benefit preventing limb amputation. Early trials injected heterogenous mononuclear cells containing a low frequency of cells with pro-vascular regenerative functions. Most trials transferred autologous cells damaged by chronic disease that demonstrated poor survival in the ischemic environment and impaired function conferred by atherosclerotic or diabetic co-morbidities. Finally, recent preclinical studies suggest optimized blood vessel formation may require paracrine and/or structural contributions from multiple progenitor cell lineages, angiocrine-secretory myeloid cells derived from hematopoietic progenitor cells, tubule-forming endothelial cells generated by circulating or vessel-resident endothelial precursors, and vessel-stabilizing perivascular cells derived from mesenchymal stem cells. Understanding how stem cells co-ordinate the myriad of cells and signals required for stable revascularization remains the key to translating the potential of stem cells into curative therapies for CLI. Thus, combination delivery of multiple cell types within supportive bioengineered matricies may represent a new direction to improve cell therapy strategies for CLI.

Hess et al. quantified circulating aldehyde dehydrogenase-expressing (ALDHhi) cell subsets in people with T2DM given either empagliflozin (EMPA) or placebo. EMPA treatment increased circulating pro-angiogenic CD133+ progenitor cells, decreased pro-inflammatory ALDHhi granulocyte precursors, and increased ALDHhi monocytes with M2 polarization. EMPA treatment improved T2DM-associated "regenerative cell depletion" contributing to enhanced vascular health.

Visual Abstract, Highlights • This study combined ALDH activity with cell surface marker expression to develop a multiparametric flow cytometry assay to assess proangiogenic progenitor and proinflammatory cell content in the peripheral blood of patients with T2D compared with age-matched control subjects. • Patients with T2D exhibited an increased frequency of proinflammatory ALDHhi cells with granulocyte side scatter properties and a decreased frequency of circulating monocytes with an M2 phenotype that is associated with proangiogenic and anti-inflammatory functions. • Patients with T2D exhibited significant depletion of circulating provascular ALDHhiCD34+ progenitor cells with primitive, migratory, endothelial, and pericyte phenotypes. • Subgroup analyses that stratified patients with T2D according to age, duration of T2D, insulin requirement, and glycosylated hemoglobin levels revealed that only the duration of T2D correlated with vascular progenitor cell depletion. • Flow cytometric assessment of circulating ALDHhi cell subsets represents a promising translational approach for identifying patients with T2D at increased risk for cardiovascular comorbidities., Summary Detection of vascular regenerative cell exhaustion is required to combat ischemic complications during type 2 diabetes mellitus (T2D). We used high aldehyde dehydrogenase (ALDH) activity and surface marker co-expression to develop a high-throughput flow cytometry–based assay to quantify circulating proangiogenic and proinflammatory cell content in the peripheral blood of individuals with T2D. Circulating proangiogenic monocytes expressing anti-inflammatory M2 markers were decreased in patients with T2D. Individuals with longer duration of T2D exhibited reduced frequencies of circulating proangiogenic ALDHhiCD34+ progenitor cells with primitive (CD133) and migratory (CXCR4) phenotypes. This approach consistently detected increased inflammatory cell burden and decreased provascular progenitor content in individuals with T2D.

Two nuclear magnetic resonance (NMR) devices, a standard imaging apparatus and a portable single-sided relaxometer (with geometry that allows non-destructive in-situ relaxation measurements on samples of any dimensions), were used to assess the hydrophobic performance of an acrylic polymer (Faraloid B- 72) applied as a trichloromethane (chloroform) solution on a biocalcarenite (Lecce stone). The NMR images and relaxation time distribution functions of samples characterized by different treatments were acquired for different water absorption and measurement sequences. Samples were analyzed both fully saturated and during the capillary water absorption. The relaxation results have been compared with NMR images of internal sections of the same samples in the same absorption conditions. In spite of the instrumental and physical differences of the two devices (the single-sided device was tuned to detect the signal from a sensitive volume that is only a small portion of the entire sample, located in the first 2 mm below the surface), the experimental results of relaxometry and imaging are in very good agreement. The comparison allows the assertion to be made that the single-sided NMR technique is a powerful tool for in-situ evaluation of water-repellent treatments used for consolidation and/or protection of stone artifacts.

NMR relaxation time distributions, obtained with laboratory and portable devices, are utilized to characterize the pore-size distributions of building materials coming from the Roman remains of the Greek-Roman Theatre of Taormina. To validate the interpretation of relaxation data in terms of pore-size distribution, comparison of results from standard and in situ NMR experiments with results of the mercury intrusion porosimetry (MIP) has been made. Although the pore-size distributions can be obtained by NMR in terms of either longitudinal (T-1) or transverse (T-2) relaxation times distributions, the shorter duration of the T-2 measurement makes it, in principle, preferable, although the determination of T-2 distributions is not necessarily an easy alternative to finding T-1 distributions. Among other things, the T-2 distribution is almost independent of the inhomogeneity of the magnetic field, while the T-2 distribution is strongly influenced by it. This paper was aimed at answering two questions: what are the validity limits to interpret NMR data in terms of pore-size distributions and whether the portable device can successfully be applied as a non-destructive and non-invasive toot for in situ NMR analysis of building materials, particularly those of Cultural Heritage interest. (C) 2007 Elsevier Inc. All rights reserved.

NMR relaxation time distributions of water 1H obtained by a portable single-sided surface device have been compared with MRI internal images obtained with a laboratory imaging apparatus on the same biocalcarenite (Lecce Stone) samples during capillary water uptake. The aim of this work was to check the ability of NMR methods to quantitatively follow the absorption phenomenon under different wettability conditions of the internal pore surfaces. Stone wettability changes were obtained by capillary absorption of a chloroform solution of Paraloid PB72, a hydrophobic acrylic resin frequently used to protect monuments and buildings, through one face of each sample. Both relaxation and imaging data have been found in good quantitative agreement each other and with masses of water determined by weighing the samples. In particular the Washburn model of water capillary rise applied to the imaging data allowed us to quantify the sorptivity in both treated and untreated samples. Combining relaxation and imaging data, a synergetic improvement of our understanding of the water absorption kinetics at both pore and sample scales is obtained. Since relaxation data have been taken over the course of time without interrupting the absorption process, simply by keeping the portable device on the surface opposite to the absorption, the results show that the single-sided NMR technique is a powerful tool for in situ evaluation of water-repellent treatments frequently used for consolidation and/or protection of stone artifacts.