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Definition: An asymptomatic patient is someone who contracts a disease but shows no symptoms. An immune subject is a person who is free from virus infection. Both of these categories of people experience the limitations of government imposed by a pandemic situation, with one important difference. Probably only the first subjects contribute, in spite of themselves, to the spread of the disease and to the contagion of the people most susceptible to the virus. This implies that their detection is essential to limit infections. Therefore, knowing the characteristics of these people and those immune to the virus can be extremely useful in mitigating the effects of the disease and/or defeating it. [ABSTRACT FROM AUTHOR]

Background: In esthetic medicine, different techniques have been used against the aging of the human skin especially in the facial area. Hyaluronic acid is used for improving the quantity of water and extracellular matrix molecule. The aim of this study is a clinical and histological evaluation of the effect of low‐molecular‐weight hyaluronic acid fragments mixed with amino acid (HAAM) on the rejuvenation the face skin treated with intradermal microinjections. Methods: Twenty women with mean age 45 range from 35 to 64 were studied, thereof 8 in menopause and 12 of childbearing age. The patients were treated with the HAAM products by mesotherapy technique; before and after 3 months of the therapeutic procedure, each patient underwent small biopsies with a circular punch biopsy. Results: The clinical results of the present study showed that the administration of the dermal filler containing fragments of hyaluronic acid between 20 and 38 monomers and amino acid via dermis injection technique produces an esthetic improvement in the faces of the treated patients, while the histological evaluation shows an increased fibroblast activity with the production of type III reticular collagen and increased number of vessels and epidermis thickness. Conclusions: The clinical and histological assessment showed that subcutaneous HAAM infiltration has a significant impact on the dermis and clinical aspects of the face. [ABSTRACT FROM AUTHOR]

Background: Stretch marks (SM) are nowadays the most common aesthetic pathology of the body; in the XX century, it mainly affected pregnant women, while today it also affects teenagers during puberty, boys and girls without distinction. The aim of this study was to evaluate possible variations in the histological structure of the skin—in terms of quality/quantity of the extracellular matrix and of the collagen and elastic fibers—following the electromagnetic fields and negative pressure (V-EMF) treatment as regards hypotonia and SMs. Materials and Methods: For the current study, 60 women, aged between 25 and 45, were examined. All of them presented deep, white or pearly white colored SMs having had them for between 12 and 25 years. These were documented, asking patients their level of satisfaction, through pictures and biopsies. All patients underwent a cycle of 6 or 8 weekly sessions; everyone was highly satisfied with the results obtained. Results: Biopsies proved that the tissue was reorganized and restored to the original volume, characterized by the production of new, high-quality collagen and elastin molecules, by the reorganization of the basement membrane and by the correct positioning of the melanocytes. No side effects were observed during the treatments. This synergy stands as the most suitable treatment of striae rubra and alba. Conclusion: V-EMF enhances the keratinocyte migration base, melanocytes, and promotes neoangiogenesis with the result of improvement in the SM. [ABSTRACT FROM AUTHOR]

The expression of molecules involved in the transductory cascade of the sense of taste (TRs, α-gustducin, PLCβ2, IP3R3) has been described in lingual taste buds or in solitary chemoreceptor cells located in different organs. At the laryngeal inlet, immunocytochemical staining at the light and electron microscope levels revealed that α-gustducin and PLCβ2 are mainly localized in chemosensory clusters (CCs), which are multicellular organizations differing from taste buds, being generally composed of two or three chemoreceptor cells. Compared with lingual taste buds, CCs are lower in height and smaller in diameter. In laryngeal CCs, immunocytochemistry using the two antibodies identified a similar cell type which appears rather unlike the α-gustducin-immunoreactive (IR) and PLCβ2-IR cells visible in lingual taste buds. The laryngeal IR cells are shorter than the lingual ones, with poorly developed basal processes and their apical process is shorter and thicker. Some cells show a flask-like shape due to the presence of a large body and the absence of basal processes. CCs lack pores and their delimitation from the surrounding epithelium is poorly evident. The demonstration of the existence of CCs strengthens the hypothesis of a phylogenetic link between gustatory and solitary chemosensory cells. [ABSTRACT FROM AUTHOR]

Seven human fetuses of crown/rump length corresponding to gestational ages ranging from the 12th to the 16th week were studied using a paradigm based on three-dimensional reconstruction of the brain obtained by magnetic resonance imaging (MRI). The aim of the study was to evaluate brain morphology in situ and to describe developmental dynamics during an important period of fetal morphogenesis. Three-dimensional MRI showed the increasing degree of maturation of the brains; fronto-occipital distance, bitemporal distance and occipital angle were examined in all the fetuses. The data were interpreted by correlation with the internal structure as visualized using high-spatial-resolution MRI, acquired using a 4.7-T field intensity magnet with a gradient power of 20 G cm−1. The spatial resolution was sufficient for a detailed detection of five layers, and the contrast was optimized using sequences with different degrees of T1 and T2 weighting. Using the latter, it was possible to visualize the subplate and marginal zones. The cortical thickness was mapped on to the hemispheric surface, describing the thickness gradient from the insular cortex to the periphery of the hemispheres. The study demonstrates the utility of MRI for studying brain development. The method provides a quantitative profiling of the brain, which allows the calculation of important morphological parameters, and it provides informative regarding transient features of the developing brain. [ABSTRACT FROM AUTHOR]

Background: The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. Methods: We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. Results: All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. Conclusions: The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia. [ABSTRACT FROM AUTHOR]

Background: Cellulite represents a common multi‐factorial condition that affects nearly all women and is now recognized as a clinical condition associated with systemic factors and negative psychological effects. Several noninvasive and minimally invasive treatments were developed during the last few years, but limited evidence supports many of them due to lack of evidence, insufficient participants, and potential adverse effects. Methods: This study aimed to evaluate the efficacy of a seaweed mud application in improving both the structure and function of tissues affected by cellulite. Sixty women with cellulite underwent 4‐week applications of seaweed mud on the buttocks and thighs. The following assessments were performed at baseline and after the last treatment: photographic, clinical, and anthropometric evaluation; tests for elasticity and hydration; ultrasonography of cellulite nodules; and cellulite biopsies in the trochanteric region. Patient satisfaction was assessed using a 5‐point Likert‐scale questionnaire. Results: The treatment resulted in a significant improvement in the severity of cellulite severity between the initial assessment and the 4‐week follow‐up, with enhanced structure, elasticity, and hydration of the affected tissues. Microscopic analysis of the cellulite biopsies revealed a significant restoration of dermal organization with induced collagen synthesis and reduced inflammation, edema, and lipid deposition following the 4‐week seaweed mud applications. Additionally, the treatment led to a remarkable improvement in comfort and satisfaction as well as a reduction in body circumferences. Conclusions: The cosmetic application of seaweed mud has proven to be a safe, non‐invasive treatment for improving the tissue alterations characteristic of cellulite. [ABSTRACT FROM AUTHOR]

Background: The appearance of striae gravidarum (SG) during pregnancy is a common problem. The most common SG are abdominal striae, which can cause the greatest sequelae after pregnancy, and in the long term. There are several solutions to prevent and treat these striae, but not all are completely effective, and not without side effects. Aims: The aim of this study was to evaluate the effectiveness of a treatment that applies an electromagnetic field under vacuum (V‐EMF therapy) on the abdominal SG. Methods: A retrospective analysis was conducted on the medical records of 26 women affected by abdominal SG and treated with V‐EMF therapy. The results were evaluated using two different 5‐point Likert Scales: one administered to the treated subjects to evaluate their satisfaction, and one to the doctors who performed the treatment, to evaluate the improvement of the striae. The presence of side effects, and the effects of sun exposure after treatment were also considered. Results: Only two treated subjects rated their level of satisfaction with a Score III on the Liker Scale. Everyone else expressed higher levels of satisfaction. Only one doctor rated the improvement of the striae with a Liker scale score of III. All the others reported greater improvements. No discomfort or side effects were noted either during the individual treatment sessions, or at the end of the treatment. The striae showed a newfound ability to tan. Conclusions: V‐EMF therapy proves to be a valid, safe, and effective treatment modality for SG. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients. [ABSTRACT FROM AUTHOR]

The presence of solitary chemosensory cells was studied in rat vallate papillae during the first week of post-natal life by α-gustducin immunocytochemistry. In 1- to 3-day-old rats, isolated α-gustducin-immunoreactive cells were found within the epithelium of the vallate papilla. These cells, mainly located in the basal layer, were scattered among keratocytes and wrapped in α-gustducin-negative epithelial cells in a glia-like fashion. The α-gustducin-immunoreactive cells were usually round and some of them gave rise to short, large processes directed towards the lumen of the oral cavity or the basal lamina. Rarely, some cells showed an evident bipolar shape. Small taste buds containing either α-gustducin-immunoreactive or α-gustducinnegative cells appeared in the vallate papillae of 4-day-old rats in which isolated, bipolar-shaped α-gustducin-immunoreactive cells were also found. After the first week of post-natal life, the taste buds appeared basically similar to those of adult animals. In conclusion, the present study demonstrates that the presence of epithelial cells with characteristics of solitary chemosensory cells precedes the development of the taste buds. [ABSTRACT FROM AUTHOR]

Background: Cellulite is a topographic alteration of the skin with unknown etiology and is characterized by the presence of a dimpled or puckered aspect, as resembling an orange peel and cottage cheese or as having mattress‐like appearance. Aim: The aim of this research was to find the different histological aspect of cellulite in sixty patients. Materials and Methods: A total of 60 women, mean age 48.8 (± 11.08) were included in the study. Among these, 11 women were in menopause (18.33%). All patients after physical examination, aesthetic, and dermatological evaluation were subjected to five cellulite biopsies with a 2.0 mm diameter and 1.5 mm in length in the trochanteric region affected by cellulite. The descriptive statistics were performed for each study predictors demographic age, height, bmi, waist, belly, hip thigh, and knee. Results: The histological analysis of the stained slides showed five different histological features were present in the most of patient. Conclusion: In conclusion, the outcome of this study shows that the histological evidence does not characterize the different states of cellulite, but several different histological aspects were present in the same patient, which effectively eliminates staging and could consider cellulite as a degenerative disease. [ABSTRACT FROM AUTHOR]

Background: Non-surgical rhinoplasty is one of the best choices in mild cases of the saddle nose, and it represents a solution for the aesthetical amelioration of facial deformity; nevertheless, in most critical cases, surgical intervention is still required. This study reports the experience and results of a single facial plastic surgeon (M.G.) using a non-surgical technique for the correction of saddle noses in a large cohort of patients. Methods: This retrospective study assesses all patients injected from January 2017 through October 2023 in private clinics in Milan (Italy), London (UK), and Dubai (UAE). All patients were followed up for 12 months. The harvested adipose tissues were processed with different systems and with or without acoustic wave therapy (AWT). The extracted products have been characterized in terms of cellular yield and cell growth. Ninety-seven patients were injected with adipose-derived products or hyaluronic acid (HA). Patients were followed up for 12 months, and satisfaction data were analyzed. Results: The stem cells obtained from the patients who previously received AWT displayed a statistically higher cell growth ability in comparison with those of the cells derived from patients who did not receive AWT. The evolution of patient satisfaction during the time for each group of treatment was investigated, and cellular treatments show the best maintenance of patient satisfaction over time. Conclusions: Dermgraft and AWT approaches resulted in the highest patient satisfaction for the non-surgical correction of the saddle nose deformity. [ABSTRACT FROM AUTHOR]

Background: Laser therapies can cause hyper- and hypopigmentation of the skin. There is little evidence in the literature of effective treatments for these types of problems in Fitzpatrick skin phototypes IV–VI. The main aim of this retrospective study is to evaluate the effects of a new therapy that combines the application of electromagnetic fields and vacuum on a subject with Fitzpatrick skin phototype VI, who presented extensive, laser-induced facial dyschromia. The secondary aim is to test the effectiveness of a free imaging software for assessing skin pigmentation. Methods: The level of improvement after therapy was evaluated, with a 5-point Likert scale, one month after the end of the treatment by the subject and by the doctor who performed the treatment, and by two blinded dermatologists. With the free software, a three-dimensional reconstruction of the treated area and the evaluation of the color distribution were performed. Results: Both the subject and the doctors involved in the study positively evaluated the effects of the treatment. The image analysis highlighted the homogenization of the skin color in the treated area. Conclusions: The combination of electromagnetic fields and vacuum for dyschromia treatments appears promising. The new method of assessing melanin levels resulted particularly efficient. [ABSTRACT FROM AUTHOR]

Given the recent evidence in the clinical application of regenerative medicine, mostly on integumentary systems, we focused our interests on recent bladder regeneration approaches based on mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and hyaluronic acid (HA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. IC/BPS is a heterogeneous chronic disease with not-well-understood etiology, characterized by suprapubic pain related to bladder filling and urothelium dysfunction, in which the impairment of immunological processes seems to play an important role. The histopathological features of IC include ulceration of the mucosa, edema, denuded urothelium, and increased detection of mast cells and other inflammatory cells. A deeper understanding of the molecular mechanism underlying this disease is essential for the selection of the right therapeutic approach. In fact, although various therapeutic strategies exist, no efficient therapy for IC/BPS has been discovered yet. This review gives an overview of the clinical and pathological features of IC/BPS, with a particular focus on the molecular pathways involved and a special interest in the ongoing few investigational therapies in IC/BPS, which use new regenerative medicine approaches, and their synergetic combination. Good knowledge of the molecular aspects related to stem cell-, PRP-, and biomaterial-based treatments, as well as the understanding of the molecular mechanism of this pathology, will allow for the selection of the right and best use of regenerative approaches of structures involving connective tissue and epithelia, as well as in other diseases. [ABSTRACT FROM AUTHOR]

Background: There are many aesthetic treatments aimed at combating aging. In the most common and frequently used ones there are often side effects, albeit minor ones. However, sometimes it is necessary to use medications before or after treatments. Objectives: To evaluate the anti‐aging efficacy and application safety of a therapy based on the combination of vacuum and electromagnetic fields (EMFs). Methods: A retrospective study was conducted to evaluate the aesthetic effects of the treatment on 217 subjects. Before treatment (T0) and after the last session (T1), skin hydration levels, the amount of sebum present and the pH were measured. The presence of discomfort during the sessions and side effects at T1 was verified. At T1, the levels of satisfaction of the patients and of the doctors who performed the treatment were assessed. At 3 and 6 months of follow‐up the aesthetic results were re‐evaluated. Results: For all treated subjects, an evident qualitative improvement was observed in the quality of the skin of the neck and face, with an increase in tone and a reduction in wrinkles. The instrumental tests highlighted a normalization of skin hydration, pH, and sebum values. High levels of satisfaction at T0 and good stability of results up to 6 months of follow‐up were reported. No discomfort was referred during the treatment sessions, nor any side effects after the entire treatment. Conclusions: The treatment that exploits the synergy between vacuum and EMFs is very promising given the effectiveness and safety of the technique. [ABSTRACT FROM AUTHOR]

Background. Stem cells from adipose tissue (ADSCs) and platelet-rich plasma (PRP) are innovative modalities that arise due to their regenerative potential. Objective. The aim of this study was to characterize possible histological changes induced by PRP and ADSC therapies in photoaged skin. Methods. A prospective randomized study involving 20 healthy individuals, showing skin aging. They underwent two therapeutic protocols (protocol 1: PRP; protocol 2: ADSCs). Biopsies were obtained before and after treatment (4 months). Results. PRP protocol showed unwanted changes in the reticular dermis, mainly due to the deposition of a horizontal layer of collagen (fibrosis) and elastic fibers tightly linked. Structural analyses revealed infiltration of mononuclear cells and depot of fibrotic material in the reticular dermis. The ADSC protocol leads to neoelastogenesis with increase of tropoelastin and fibrillin. There was an improvement of solar elastosis inducing an increment of macrophage polarization and matrix proteinases. These last effects are probably related to the increase of elastinolysis and the remodeling of the dermis. Conclusions. The PRP promoted an inflammatory process with an increase of reticular dermis thickness with a fibrotic aspect. On the other hand, ADSC therapy is a promising modality with an important antiaging effect on photoaged human skin. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells extracted from adipose tissue are particularly promising given the ease of harvest by standard liposuction and reduced donor site morbidity. This study proposes a novel enzymatic method for isolating stem cells using Vibrio alginolyticus collagenase, obtaining a high-quality product in a reduced time. Initially, the enzyme concentration and incubation time were studied by comparing cellular yield, proliferation, and clonogenic capacities. The optimized protocol was phenotypically characterized, and its ability to differentiate in the mesodermal lineages was evaluated. Subsequently, that protocol was compared with two Clostridium histolyticum-based collagenases, and other tests for cellular integrity were performed to evaluate the enzyme's effect on expanded cells. The best results showed that using a concentration of 3.6 mg/mL Vibrio alginolyticus collagenase allows extracting stem cells from adipose tissue after 20 min of enzymatic reaction like those obtained with Clostridium histolyticum-based collagenases after 45 min. Moreover, the extracted cells with Vibrio alginolyticus collagenase presented the phenotypic characteristics of stem cells that remain after culture conditions. Finally, it was seen that Vibrio alginolyticus collagenase does not reduce the vitality of expanded cells as Clostridium histolyticum-based collagenase does. These findings suggest that Vibrio alginolyticus collagenase has great potential in regenerative medicine, given its degradation selectivity by protecting vital structures for tissue restructuration. [ABSTRACT FROM AUTHOR]

TiO2–Ag doped nanoparticulate (TiO2–Ag–NP) adhesive photocatalytic films were used to assess the ability in dropping down the burden of indoor microbial particles. The application of an easy-to use photocatalytic adhesive film to cleanse indoor living spaces from microbial pollution, represents a novelty in the field of photocatalytic devices. Reduction was attained by photocatalysis in selected spaces, usually with overcrowding (≥ 3 individuals) in the common working daily hours, and upon indoor microclimate monitoring. TiO2–Ag doped nanoparticulate (TiO2–Ag–NP) adhesive photocatalytic films were applied within five types of living spaces, including schools and job places. The microbial pollution was assessed at time 0 (far from routine clean, ≥ 9 h) and throughout 2–4 weeks following the photocatalyst application by relative light unit (RLU) luminometry and microbial indirect assessment (colony forming units per cubic meter, CFU/m3). TiO2–Ag–NP photocatalyst reduced RLU and CFU/m3 by rates higher than 70% leading to RLU ≤ 20 and microbial presence ≤ 35 CFU/m3. The described TiO2–Ag–NP is able to reduce microbial pollution to the lowest RLU threshold (≤ 20) within 60 min in open daylight in a standardized test room of 100 m2. The correlation between RLU and CFU/m3 was positive (r = 0.5545, p < 0.05), assessing that the microbial reduction of indoor areas by the TiO2–Ag–NP adhesive film was real. Titania photocatalysts represent promising tools to ensure air cleaning and sanitization in living indoor microclimates with a low cost, feasible and straightforward approach. This approach represents an easy to handle, cost effective, feasible and efficacious approach to reduce microbial pollution in indoor spaces, by simply attaching a TiO2–Ag–NP adhesive film on the wall. [ABSTRACT FROM AUTHOR]

The auditory brainstem implant (ABI) can provide hearing sensation to individuals where the auditory nerve is damaged. However, patient outcomes with the ABI are typically much poorer than those for cochlear implant recipients. A major limitation to ABI outcomes is the number of implanted electrodes that can produce auditory responses to electric stimulation. One of the greatest challenges in ABI surgery is the intraoperative positioning of the electrode paddle, which must fit snugly within the cochlear nucleus complex. While there presently is no optimal procedure for intraoperative electrode positioning, intraoperative assessments may provide useful information regarding viable electrodes that may be included in patients' clinical speech processors. Currently, there is limited knowledge regarding the relationship between intraoperative data and post-operative outcomes. Furthermore, the relationship between initial ABI stimulation with and long-term perceptual outcomes is unknown. In this retrospective study, we reviewed intraoperative electrophysiological data from 24 ABI patients (16 adults and 8 children) obtained with two stimulation approaches that differed in terms of neural recruitment. The interoperative electrophysiological recordings were used to estimate the number of viable electrodes and were compared to the number of activated electrodes at initial clinical fitting. Regardless of the stimulation approach, the intraoperative estimate of viable electrodes greatly overestimated the number of active electrodes in the clinical map. The number of active electrodes was associated with long-term perceptual outcomes. Among patients with 10-year follow-up, at least 11/21 active electrodes were needed to support good word detection and closed-set recognition and 14/21 electrodes to support good open-set word and sentence recognition. Perceptual outcomes were better for children than for adults, despite a lower number of active electrodes. [ABSTRACT FROM AUTHOR]

Acid attacks are on the rise, and they cause extensive and deep burns, especially on the face. The treatments used to improve the aesthetic, functional and social impact of non-acid scars do not always prove useful for acid scars. This article reports the case of a woman with an extended, mature, acid facial scar, caused by sulfuric acid assault, treated with a recent new procedure that combines the application of vacuum and electromagnetic fields. Before and after the treatment, the aesthetic appearance, and motor function of the face and neck were evaluated, as well as the level of hydration, the amount of sebum, the elasticity, and the pH of the skin. The improvements highlighted after the treatment of the aesthetic and functional characteristics of the face and neck, and of the physical parameters of the skin seemed to indicate that this particular treatment induces tissue regeneration, even in the nerve component. However, it is evident that the rehabilitation pathways of facial wounds and scars must be personalized, and must include continuous psychological support for the patient. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 replicates in host cell cytoplasm. People with cystic fibrosis, considered at risk of developing severe symptoms of COVID-19, instead, tend to show mild symptoms. We, thus, analyzed at the ultrastructural level the morphological effects of SARS-CoV-2 infection on wild-type (WT) and F508del (ΔF) CFTR-expressing CFBE41o- cells at early and late time points post infection. We also investigated ACE2 expression through immune-electron microscopy. At early times of infection, WT cells exhibited double-membrane vesicles, representing typical replicative structures, with granular and vesicular content, while at late time points, they contained vesicles with viral particles. ∆F cells exhibited double-membrane vesicles with an irregular shape and degenerative changes and at late time of infection, showed vesicles containing viruses lacking a regular structure and a well-organized distribution. ACE2 was expressed at the plasma membrane and present in the cytoplasm only at early times in WT, while it persisted even at late times of infection in ΔF cells. The autophagosome content also differed between the cells: in WT cells, it comprised vesicles associated with virus-containing structures, while in ΔF cells, it comprised ingested material for lysosomal digestion. Our data suggest that CFTR-modified cells infected with SARS-CoV-2 have impaired organization of normo-conformed replicative structures. [ABSTRACT FROM AUTHOR]

People with cystic fibrosis should be considered at increased risk of developing severe symptoms of COVID-19. Strikingly, a broad array of evidence shows reduced spread of SARS-CoV-2 in these subjects, suggesting a potential role for CFTR in the regulation of SARS-CoV-2 infection/replication. Here, we analyzed SARS-CoV-2 replication in wild-type and CFTR-modified human bronchial epithelial cell lines and primary cells to investigate SARS-CoV-2 infection in people with cystic fibrosis. Both immortalized and primary human bronchial epithelial cells expressing wt or F508del-CFTR along with CRISPR/Cas9 CFTR-ablated clones were infected with SARS-CoV-2 and samples were harvested before and from 24 to 72 h post-infection. CFTR function was also inhibited in wt-CFTR cells with the CFTR-specific inhibitor IOWH-032 and partially restored in F508del-CFTR cells with a combination of CFTR modulators (VX-661+VX-445). Viral load was evaluated by real-time RT-PCR in both supernatant and cell extracts, and ACE-2 expression was analyzed by both western blotting and flow cytometry. SARS-CoV-2 replication was reduced in CFTR-modified bronchial cells compared with wild-type cell lines. No major difference in ACE-2 expression was detected before infection between wild-type and CFTR-modified cells, while a higher expression in wild-type compared to CFTR-modified cells was detectable at 72 h post-infection. Furthermore, inhibition of CFTR channel function elicited significant inhibition of viral replication in cells with wt-CFTR, and correction of CFTR function in F508del-CFTR cells increased the release of SARS-CoV-2 viral particles. Our study provides evidence that CFTR expression/function is involved in the regulation of SARS-CoV-2 replication, thus providing novel insights into the role of CFTR in SARS-CoV-2 infection and the development of therapeutic strategies for COVID-19. [ABSTRACT FROM AUTHOR]

The diffuse chemosensory system (DCS) of the respiratory apparatus is composed of solitary chemosensory cells (SCCs) that resemble taste cells but are not organized in end organs. The discovery of the DCS may open up new approaches to respiratory diseases. However, available data on mammalian SCCs have so far been collected from rodents, the airways of which display some differences from those of large mammals. Here we investigated the presence of the DCS and of SCCs in cows and bulls ( Bos taurus), in which the airway cytology is similar to that in humans, focusing our attention on detection in the airways of molecules involved in the transduction cascade of taste [i.e. α-gustducin and phospholipase C of the β2 subtype (PLCβ2)]. The aim of the research was to extend our understanding of airway chemoreceptors and to compare the organization of the DCS in a large mammal with that in rodents. Using immunocytochemistry for α-gustducin, the taste buds of the tongue and arytenoid were visualized. In the trachea and bronchi, α-gustducin-immunoreactive SCCs were frequently found. Using immunocytochemistry for PLCβ2, the staining pattern was generally similar to those seen for α-gustducin. Immunoblotting confirmed the expression of α-gustducin in the tongue and in all the airway regions tested. The study demonstrated the presence of SCCs in cows and bulls, suggesting that DCSs are present in many mammalian species. The description of areas with a high density of SCCs in bovine bronchi seems to indicate that the view of the DCS as made up of isolated cells totally devoid of ancillary elements is probably an oversimplification. [ABSTRACT FROM AUTHOR]

Keywords: elastosonography; non-invasive diagnostic system; skin elasticity; strain elastography; subcutis EN elastosonography non-invasive diagnostic system skin elasticity strain elastography subcutis 641 643 3 07/29/21 20210701 NES 210701 Dermatological diseases often affect not only the superficial part of the dermis but deepen into the hypodermis and sometimes also involve the muscle bundles. The displacement allows to evaluate the elasticity of the skin, since the soft tissues move more than the stiff tissues in response to this type of stimulus. [Extracted from the article]

Basic, translational, and clinical research in the area of stem cell biology is currently aimed at investigating the ability of adipose stem cells (ASCs) to enhance tissue and organ regeneration and suggest that ASCs in 3D scaffolds may have potential for application in wound healing, orthopaedic tissue repair, and tissue reconstruction after surgery [[1]]. The development of regenerative medicine strategies requires an appropriate phenotypically stable and well-characterized cell source and a 3-dimensional scaffold or "smart" biomaterial (novel "intelligent" biomaterial with appropriate physical properties that can support I in vivo i the commitment of ASCs), together with a suitable microenvironment to provide the necessary cues and signals for cell growth and tissue formation. However, 3D tissue engineering scaffolds are better able to mimic the in vivo cellular microenvironment and more effectively recapitulate the physiological setting, resulting in improved localization, attachment, proliferation, and differentiation of ASCs. [Extracted from the article]

Telomerase (TERT) is overexpressed in 80% to 90% of primary tumors and contributes to sustaining the transformed phenotype. The identification of several TERT epitopes in tumor cells has elevated the status of TERT as a potential universal target for selective and broad adoptive immunotherapy. TERT-specific cytotoxic T lymphocytes (CTL) have been detected in the peripheral blood of B-cell chronic lymphocytic leukemia (B-CLL) patients, but display low functional avidity, which limits their clinical utility in adoptive cell transfer approaches. To overcome this key obstacle hindering effective immunotherapy, we isolated an HLA-A2-restricted T-cell receptor (TCR) with high avidity for human TERT from vaccinated HLA-A 0201 transgenic mice. Using several relevant humanized mouse models, we demonstrate that TCR-transduced T cells were able to control human BCLL progression in vivo and limited tumor growth in several human, solid transplantable cancers. TERT-based adoptive immunotherapy selectively eliminated tumor cells, failed to trigger a self-MHC-restricted fratricide of T cells, and was associated with toxicity against mature granulocytes, but not toward human hematopoietic progenitors in humanized immune reconstituted mice. These data support the feasibility of TERT-based adoptive immunotherapy in clinical oncology, highlighting, for the first time, the possibility of utilizing a high-avidity TCR specific for human TERT. Cancer Res; 76(9); 2540-51. [ABSTRACT FROM AUTHOR]

Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles (MNPs) are capable of generate heating power under the influence of alternating magnetic fields (AMF); this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs): a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI) to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Multipotent stem cells persist within the stromal vascular fraction (SVF) of adipose tissue during adulthood. These cells, commonly referred to as adipose-derived stromal cells (ASC), have been extensively investigated over the past years as a promising therapeutic tool based on their regenerative and immunomodulatory properties. However, how ASC might mirror the age-related alteration of the fat they reside in remains unclear. Herein, we show that inguinal adipose tissue in mice turns from brown/beige- to white-like with age and resident ASC readily mirror these changes both at mRNA and microRNA transcriptional level. Mechanistically, our data suggest that these brown/age-related changes in ASC transcription rely on changes in the activity of E2F1 and NFkB transcription factors. • mRNA and microRNA transcriptome of adipose-derived stromal cells (ASC) mirror the whitening of inguinal fat pad with age. • Whitening/aging transcriptional changes relates dysregulated activity of NFkB and E2F1 transcription factors. • Aging-induced transcriptional changes in adipose-derived stromal cells (ASC) overlap signatures of metabolic dysfunctions. [ABSTRACT FROM AUTHOR]

Reference 1 De Francesco F., Riccio V., Biswas R., Busato A., Di Bella C., Serri E., Sbarbati A., Zavan B., Riccio M., Palumbo Piccionello A. In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions. The corrected Author Contributions Statement appears here. In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions. [Extracted from the article]

One of the mechanisms that characterizes the aging process of different organs is the accumulation of fat. Different authors have demonstrated that adipose tissue replaces the loss of other cell types, deriving from mesenchymal cells. During aging, there is substitution or trans-differentiation of mesenchymal cells with other cells having the same embryological origin. Newly formed adipocytes were also observed in the trabecular matrix of elderly people's bones, associated with myeloid cells. In this study, we have investigated the relationship between immature myeloid-derived suppressor cells (I-MDSCs) and mesenchymal stem cells (MSCs) in bone marrow (BM) samples harvested from 57 patients subjected to different orthopedic surgeries. Patients aged from 18 to 92 years were considered in order to compare the cellular composition of bone marrow of young and elderly people, considered a biomarker of immunity, inflammation, and bone preservation. The I-MDSC percentage was stable during aging, but in elderly people, it was possible to observe a strong basal immunosuppression of autologous and heterologous T cells' proliferation. We hypothesized that this pattern observed in elders depends on the progressive accumulation in the BM of activating stimuli, including cell–cell contact, or the production of different cytokines and proteins that induce the differentiation of bone marrow mesenchymal stem cells in adipocytes. The collected data provided underline the importance of specific biomarkers of aging that promote a reduction in immune response and incremented inflammatory pathways, leading to bone reabsorption in elderly people. [ABSTRACT FROM AUTHOR]

Simple Summary: Mesenchymal stem cells are located in bone marrow, adipose tissue, synovial membrane, and muscular tissue. They have an immunosuppressive, anti-inflammatory, and antifibrotic effect. Tissue engineering considers the usage of mesenchymal stem cells as a possible option for regenerating tissues, with respect to bone and cartilage, due to their ability to differentiate into multiple cytotypes (including chondrocytes and osteoblasts). Herein, we characterize a non-invasive solution based on Rigenera® technology, a mechanical disaggregation method able to produce autologous adipose tissue-derived micrografts which are analogous to adipose-derived stem cells. Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses. [ABSTRACT FROM AUTHOR]

Glucose transport plays an important role in maintaining low sugar concentration in airway surface liquid (ASL), which is critical for mucociliary clearance and bacterial colonization. Experimental evidence indicates that glucose/hexose uptake in lung/airway cells occurs by means of two structurally distinct glucose transporter pathways: the Na+-dependent glucose transporters (SGLT family) and the facilitative glucose transporters (GLUT family). In this study, we examined the expression of the major glucose transporters of the intestine, GLUT2, GLUT5, SGLT1 and T1R3 taste receptor subunit, in the trachea of rats using immunohistochemistry and immunoelectron microscopy, and compared them using double-labeled confocal microscopy. We found that GLUT2, GLUT5, SGLT1 and T1R3 are selectively expressed in different cell types. T1R3 and GLUT2 are predominantly expressed in subsets of solitary chemoreceptor cells (SCCs) and ciliated cells, GLUT5 is present in subsets of SCCs and in secretory cells, and SGLT1 is exclusively expressed in a unique cell type, SCCs. Furthermore, we demonstrated that T1R3 is colocalized with SGLT1 in SCCs and with GLUT2 transporter in ciliated cells. In conclusion, these findings reveal that different cell types are associated with the uptake of glucose in ASL and that, due to their T1R3 expression, SCCs and ciliated cells are most likely to participate in the chemosensory process in ASL. [ABSTRACT FROM AUTHOR]

To date there is a lack of tools to map the spatio-temporal dynamics of diverse cells in experimental heart models. Conventional histology is labor intensive with limited coverage, whereas many imaging techniques do not have sufficiently high enough spatial resolution to map cell distributions. We have designed and built a high resolution, dual channel Born-normalized near-infrared fluorescence optical projection tomography system to quantitatively and spatially resolve molecular agents distribution within whole murine heart. We validated the use of the system in a mouse model of monocytes/macrophages recruitment during myocardial infarction. While acquired, data were processed and reconstructed in real time. Tomographic analysis and visualization of the key inflammatory components were obtained via a mathematical formalism based on left ventricular modeling. We observed extensive monocyte recruitment within and around the infarcted areas and discovered that monocytes were also extensively recruited into non-ischemic myocardium, beyond that of injured tissue, such as the septum. [ABSTRACT FROM AUTHOR]

Heel fat pad cushioning efficiency is the result of its structure, shape and thickness. However, while a number of studies have investigated heel fat pad (HFP) anatomy, structural behavior and material properties, no previous study has described its three-dimensional morphology in situ. The assessment of the healthy, unloaded, three-dimensional morphology of heel pad may contribute to deepen the understanding of its role and behavior during locomotion. It is the basis for the assessment of possible HFP morphological modifications due to changes in the amount or distribution of the loads normally sustained by the foot. It may also help in guiding the surgical reconstruction of the pad and in improving footwear design, as well as in developing a correct heel pad geometry for finite element models of the foot. Therefore the purpose of this study was to obtain a complete analysis of HFP three-dimensional morphology in situ. The right foot of nine healthy volunteers was scanned with computed tomography. A methodological approach that maximizes reliability and repeatability of the data was developed by building a device to lock the foot in a neutral position with respect to the scan planes during image acquisition. Scan data were used to reconstruct virtual three-dimensional models for both the calcaneus and HFP. A set of virtual coronal and axial sections were extracted from the three-dimensional model of each HFP and processed to extract a set of one- and two-dimensional morphometrical measurements for a detailed description of heel pad morphology. The tissue exhibited a consistent and sophisticated morphology that may reflect the biomechanics of the foot support. HFP was found to be have a crest on its anterior dorsal surface, flanges on the sides and posteriorly, and a thick portion that reached and covered the posterior surface of the calcaneus and the achilles tendon insertion. Its anterior internal portion was thinner and a lump of fat was consistently present in this region. Finally, HFP was found to be thicker in males than in females. [ABSTRACT FROM AUTHOR]

In the intestine, changes of sugar concentration generated in the lumen during digestion induce adaptive responses of glucose transporters in the epithelium. A close matching between the intestinal expression of glucose transporters and the composition and amount of the diet has been provided by several experiments. Functional evidence has demonstrated that the regulation of glucose transporters into enterocytes is induced by the sensing of sugar of the enteroendocrine cells through activation of sweet taste receptors (T1R2 and T1R3) and their associated elements of G-protein-linked signaling pathways (e.g. α-gustducin, phospholipase C β type 2 and transient receptor potential channel M5), which are signaling molecules also involved in the perception of sweet substances in the taste receptor cells (TRCs) of the tongue. Considering this phenotypical similarity between the intestinal cells and TRCs, we evaluated whether the TRCs themselves possess proteins of the glucose transport mechanism. Therefore, we investigated the expression of the typical intestinal glucose transporters (i.e. GLUT2, GLUT5 and SGLT1) in rat circumvallate papillae, using immunohistochemistry, double-labeling immunofluorescence, immunoelectron microscopy and reverse transcriptase-polymerase chain reaction analysis. The results showed that GLUT2, GLUT5 and SGLT1 are expressed in TRCs; their immunoreactivity was also observed in cells that displayed staining for a-gustducin and T1R3 receptor. The immunoelectron microscopic results confirmed that GLUT2, GLUT5 and SGLT1 were predominantly expressed in cells with ultrastructural characteristics of chemoreceptor cells. The presence of glucose transporters in TRCs adds a further link between chemosensory information and cellular responses to sweet stimuli that may have important roles in glucose homeostasis, contributing to a better understanding of the pathways implicated in glucose metabolism. [ABSTRACT FROM AUTHOR]

Background: Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm. Methodology/Principal Findings: By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies. Conclusions/Significance: Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis. [ABSTRACT FROM AUTHOR]

Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE) is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a) whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS) and b) whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22) months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy. [ABSTRACT FROM AUTHOR]

The oral cavity is continuously bathed by saliva secreted by the major and minor salivary glands. Saliva is the first biological medium to confront external materials that are taken into the body as part of food or drink or inhaled volatile substances, and it contributes to the first line of oral defence. In humans, it has been shown that sputum and a variety of biological fluids contain Clara cell secretory proteins (CC10–CC26). Various studies of the respiratory apparatus have suggested their protective effect against inflammatory response and oxidative stress. Recently, CC10 deficiency has been related to the protein Annexin-1 (ANXA1), which has immunomodulatory and anti-inflammatory properties. Considering the defensive role of both Clara cell secretory proteins and ANXA1 in the respiratory apparatus, and the importance of salivary gland secretion in the first line of oral defence, we decided to evaluate the expression of CC10, CC26 and ANXA1 proteins in rat major salivary glands using immunohistochemistry. CC10 expression was found only in the ductal component of the sublingual gland. Parotid and submandibular glands consistently lacked CC10 immunoreactivity. In the parotid gland, both acinar and ductal cells were always CC26-negative, whereas in the submandibular gland, immunostaining was localized in the ductal component and in the periodic acid Schiff (PAS)-positive area. In the sublingual gland, ductal cells were always positive. Acinar cells were not immunostained at all. ANXA1 was expressed in ductal cells in all three major glands. In parotid and sublingual glands, acinar cells were negative. In submandibular glands, immunostaining was present in the mucous PAS-positive portion, whereas serous acinar cells were consistently negative. The existence of some CC10-CC26–ANXA1-positive cells in rat salivary glandular tissue is an interesting preliminary finding which could support the hypothesis, suggested for airway tissue, that these proteins have a defensive and protective role. Protein expression heterogeneity in the different portions of the glands could be an important clue in further investigations of their role. [ABSTRACT FROM AUTHOR]

Summary: Objective: This paper presents Visual MRI, an innovative tool for the magnetic resonance imaging (MRI) analysis of tumoral tissues. The main goal of the analysis is to separate each magnetic resonance image in meaningful clusters, highlighting zones which are more probably related with the cancer evolution. Such non-invasive analysis serves to address novel cancer treatments, resulting in a less destabilizing and more effective type of therapy than the chemotherapy-based ones. The advancements brought by Visual MRI are two: first, it is an integration of effective information visualization (IV) techniques into a clustering framework, which separates each MRI image in a set of informative clusters; the second improvement relies in the clustering framework itself, which is derived from a recently re-discovered non-parametric grouping strategy, i.e., the mean shift. Methodology: The proposed methodology merges visualization methods and data mining techniques, providing a computational framework that allows the physician to move effectively from the MRI image to the images displaying the derived parameter space. An unsupervised non-parametric clustering algorithm, derived from the mean shift paradigm, and called MRI-mean shift, is the novel data mining technique proposed here. The main underlying idea of such approach is that the parameter space is regarded as an empirical probability density function to estimate: the possible separate modes and their attraction basins represent separated clusters. The mean shift algorithm needs sensibility threshold values to be set, which could lead to highly different segmentation results. Usually, these values are set by hands. Here, with the MRI-mean shift algorithm, we propose a strategy based on a structured optimality criterion which faces effectively this issue, resulting in a completely unsupervised clustering framework. A linked brushing visualization technique is then used for representing clusters on the parameter space and on the MRI image, where physicians can observe further anatomical details. In order to allow the physician to easily use all the analysis and visualization tools, a visual interface has been designed and implemented, resulting in a computational framework susceptible of evaluation and testing by physicians. Results: Visual MRI has been adopted by physicians in a real clinical research setting. To describe the main features of the system, some examples of usage on real cases are shown, following step by step all the actions scientists can do on an MRI image. To assess the contribution of Visual MRI given to the research setting, a validation of the clustering results in a medical sense has been carried out. Conclusions: From a general point of view, the two main objectives reached in this paper are: (1) merging information visualization and data mining approaches to support clinical research and (2) proposing an effective and fully automated clustering technique. More particularly, a new application for MRI data analysis, named Visual MRI, is proposed, aiming at improving the support of medical researchers in the context of cancer therapy; moreover, a non-parametric technique for cluster analysis, named MRI-mean shift, has been drawn. The results show the effectiveness and the efficacy of the proposed application. [Copyright &y& Elsevier]

Osteoarthritis (OA) is a chronic debilitating disorder causing pain and gradual degeneration of weight-bearing joints with detrimental effects on cartilage volume as well as cartilage damage, generating inflammation in the joint structure. The etiology of OA is multifactorial. Currently, therapies are mainly addressing the physical and occupational aspects of osteoarthritis using pharmacologic pain treatment and/or surgery to manage the symptomatology of the disease with no specific regard to disease progression or prevention. Herein, we highlight alternative therapeutics for OA specifically considering innovative and encouraging translational methods with the use of adipose mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

The autologous lipoaspirate processing allows to obtain a tissue product to be transplanted for regenerative purposes in multiple pathological sites, such as the knee joint affected by osteoarthritic disease. Recently, multiple protocols and devices have been designed for lipoaspirate processing. These protocols and devices do not use enzymatic digestion and respect the principles of the so-called "minimal manipulation in a closed system". In this study, we performed a systematic review of the literature to identify studies in which osteoarthritis was treated by minimally manipulated intra-articular SVF injection and assessment of therapeutic response was reported. All bias scores were analyzed based on the Coleman methodology score modified by Kon et al. [27] and a subsequent linear classification system of articles was proposed. We identified 12 clinical trials in which clinical evaluations were performed inconsistently using different scales of analysis. All studies reported a significant decrease in the patient's symptomatic discomfort, with improvement in joint function and reduction in pain. Most studies do not reach a high-quality level on the linear scale based on the Coleman-Kon scores. Although the treatment of osteoarthritis of the knee with regenerative methods is undoubtedly of interest, being aimed at healing the disease, this study highlights that the trials are numerically limited, and qualitatively not optimal according to the Coleman-Kon score. Reasonably, greater standardization of devices protocols will be desirable in the future. The high clinical potential offered by these methods could be optimized for all patients. [Display omitted] • Non-enzymatically treated adipose tissue is poorly documented for knee osteoarthritis. • These studies do not exhibit optimal protocols, based on the Coleman-Kon score. • After treatment, clinical improvement is reported in all available studies. • No standard protocol for lipoaspirate therapy is currently defined. [ABSTRACT FROM AUTHOR]

Taste receptor cells (TRCs) are the sensory cells of taste transduction and are organized into taste buds embedded in the epithelium of the tongue, palate, pharynx, and larynx. Several studies have demonstrated that TRCs involved in sweet as well as bitter and umami responses express α-gustducin, an α-subunit of the G-protein complex. It has been further demonstrated that this typical taste protein is a potent marker of chemosensory cells located in several tissues, including gastric and pancreatic mucosa and the respiratory apparatus. We recently observed that α-gustducin and phospholipase C beta 2–immunoreactive cells were colocalized in the airways with cystic fibrosis transmembrane regulator (CFTR) and Clara cell–specific secretory protein of 10 (CC10) and 26 kDa (CC26). This finding suggests that TRCs might themselves express secretory markers. To test this hypothesis, we investigated the expression of CFTR, CC10, and CC26 in rat circumvallate papillae using reverse transcriptase–polymerase chain reaction analysis, immunohistochemistry, and confocal laser microscopy. The results showed that secretory markers such as CFTR, CC10, and CC26 are present in taste cells of rat circumvallate papillae, and their immunoreactivity is expressed, to a different extent, in subsets of taste cells that express α-gustducin. The presence of CFTR, CC10, and CC26 in taste bud cells and their coexpression pattern with α-gustducin confirms and extends our previous findings in airway epithelium, lending further credence to the notion that chemoreception and secretion may be related processes. [ABSTRACT FROM AUTHOR]

Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/ metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of "mesenchymalization" such as desmoplasia or epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

A new type of magnetic resonance imaging analysis, based on fusion of three-dimensional reconstructions of time-to-peak parametric maps and high-resolution T1-weighted images, is proposed in order to evaluate the perfusion of selected volumes of interest. Because in recent years a wealth of data have suggested the crucial involvement of vascular alterations in mental diseases, we tested our new method on a restricted sample of schizophrenic patients and matched healthy controls. The perfusion of the whole brain was compared with that of the caudate nucleus by means of intrasubject analysis. As expected, owing to the encephalic vascular pattern, a significantly lower time-to-peak was observed in the caudate nucleus than in the whole brain in all healthy controls, indicating that the suggested method has enough sensitivity to detect subtle perfusion changes even in small volumes of interest. Interestingly, a less uniform pattern was observed in the schizophrenic patients. The latter finding needs to be replicated in an adequate number of subjects. In summary, the three-dimensional analysis method we propose has been shown to be a feasible tool for revealing subtle vascular changes both in normal subjects and in pathological conditions. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 µm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes. [ABSTRACT FROM AUTHOR]

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched-chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the ‘sterile’ activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age. [ABSTRACT FROM AUTHOR]

The stromal vascular fraction (SVF) consists of a heterogeneous population of stem and stromal cells, generally obtained from adipose tissue by enzymatic digestion. For human cell-based therapies, mechanical process methods to obtain SVF represent an advantageous approach because they have fewer regulatory restrictions for their clinical use. The aim of this study was to characterize a novel commercial system for obtaining SVF from adipose tissue by a mechanical approach without substantial manipulations. Lipoaspirate samples collected from 27 informed patients were processed by a simple and fast mechanical system (by means of Hy-Tissue SVF). The Hy-Tissue SVF product contained a free cell fraction and micro-fragments of stromal connective tissue. The enzymatic digestion of the micro-fragments increased the yield of free cells (3.2 times) and CFU-F (2.4 times). Additionally, 10% of free cells from SVF were positive for CD34+, suggesting the presence of endothelial cells, pericytes, and potential adipose-derived stem cells (ADSC). Moreover, the SVF cells were able to proliferate and differentiate in vitro toward adipocytes, osteocytes, and chondrocytes. The immunophenotypic analysis of expanded cells showed positivity for typical mesenchymal stem cell markers. The Hy-Tissue SVF system allows the isolation of stromal vascular fraction, making this product of potential interest in regenerative medicine. [ABSTRACT FROM AUTHOR]