Long-term effects of SARS-CoV-2 infection in patients with and without chemosensory disorders at disease onset: a psychophysical and magnetic resonance imaging exploratory study.

A preserved sense of smell and taste allows us to understand many environmental "messages" and results in meaningfully improvements to quality of life. With the COVID-19 pandemic, it became clear how important these senses are for social and nutritional status and catapulted this niche chemosensory research area towards widespread interest. In the current exploratory work, we assessed two groups of post-COVID-19 patients who reported having had (Group 1) or not (Group 2) a smell/taste impairment at the disease onset. The aim was to compare them using validated smell and taste tests as well as with brain magnetic resonance imaging volumetric analysis. Normative data were used for smell scores comparison and a pool of healthy subjects, recruited before the pandemic, served as controls for taste scores. The majority of patients in both groups showed an olfactory impairment, which was more severe in Group 1 (median UPSIT scores: 24.5 Group 1 vs 31.0 Group 2, p = 0.008), particularly among women (p = 0.014). No significant differences emerged comparing taste scores between Group 1 and Group 2, but dysgeusia was only present in Group 1 patients. However, for taste scores, a significant difference was found between Group 1 and controls (p = 0.005). No MRI anatomical abnormalities emerged in any patients while brain volumetric analysis suggested a significant difference among groups for the right caudate nucleus (p = 0.028), although this was not retained following Benjamini-Hochberg correction. This exploratory study could add new information in COVID-19 chemosensory long-lasting impairment and address future investigations on the post-COVID-19 patients' research.

Anatomy, Histology, and Embryonic Origin of Adipose Tissue: Insights to Understand Adipose Tissue Homofunctionality in Regeneration and Therapies.

Preadipocytes are formed during the 14th and 16th weeks of gestation. White adipose tissue, in particular, is generated in specific areas and thereby assembles after birth, rapidly increasing following the propagation of adipoblasts, which are considered the preadipocyte cell precursors. The second trimester of gestation is a fundamental phase of adipogenesis, and in the third trimester, adipocytes, albeit small may be present within the main deposition areas. In the course of late gestation, adipose tissue develops in the foetus and promotes the synthesis of large amounts of uncoupling protein 1, in similar quantities relative to differentiated brown adipose tissue. In mammals, differentiation occurs in two functionally different types of adipose cells: white adipose cells resulting from lipid storage and brown adipose cells from increased metabolic energy consumption. During skeletogenesis, synovial joints develop through the condensation of mesenchymal cells, which forms an insertional layer of flattened cells that umlaut skeletal elements, by sharing the same origin in the development of synovium. Peri-articular fat pads possess structural similarity with body subcutaneous white adipose tissue; however, they exhibit a distinct metabolic function due to the micro-environmental cues in which they are embedded. Fat pads are an important component of the synovial joint and play a key role in the maintenance of joint homeostasis. They are also implicated in pathological states such as osteoarthritis.In this paper we explore the therapeutic potential of adipocyte tissue mesenchymal precursor-based stem cell therapy linking it back to the anatomic origin of adipose tissue.

Mechanical Purification of Lipofilling: The Relationship Between Cell Yield, Cell Growth, and Fat Volume Maintenance.

BACKGROUND: The mechanical manipulations of fat tissue represented from centrifugation, filtration, washing, and fragmentation were considered the most effective strategies aiming to obtain purified lipofilling with different impacts both in terms of adipose-derived stem cells amount contained in stromal vascular fraction, and fat volume maintenance. OBJECTIVES: The present work aimed to report results in fat volume maintenance obtained by lipofilling purification based on the combined use of washing and filtration, in a clinical study, and to deeply investigate the adipose-derived stem cells yield and growth capacity of the different stromal vascular fraction extraction techniques with an in vitro approach. METHODS: A preliminary prospective, case-control study was conducted. 20 patients affected by face and breast soft tissue defects were treated with lipofilling and divided into two groups: n = 10 patients (study group) were treated with lipofilling obtained by washing and filtration procedures, while n = 10 (control group) were treated with lipofilling obtained by centrifugation according to the Coleman technique. 6 months after the lipofilling, the volume maintenance percentage was analyzed by clinical picture and magnetic resonance imaging comparisons. Additionally, extracted stromal vascular fraction cells were also in vitro analyzed in terms of adipose-derived stem cell yield and growth capacity. RESULTS: A 69% ± 5.0% maintenance of fat volume after 6 months was observed in the study group, compared with 44% ± 5.5% in the control group. Moreover, the cellular yield of the control group resulted in 267,000 ± 94,107 adipose-derived stem cells/mL, while the study group resulted in 528,895 ± 115,853 adipose-derived stem cells /mL, with a p-value = 0.1805. Interestingly, the study group showed a fold increase in cell growth of 6758 ± 0.7122, while the control group resulted in 3888 ± 0.3078, with a p < 0.05 (p = 0.0122). CONCLUSIONS: The comparison of both groups indicated that washing and filtration were a better efficient system in lipofilling preparation, compared to centrifugation, both in terms of volume maintenance and adipose-derived stem cell growth ability. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

The Use of Cross-Linked Hyaluronic Acid in Non-surgical Rhinoplasty Using Italian Technique.

INTRODUCTION: Projection and upper rotation to the tip is fundamental in the nasal rejuvenation, as a matter of fact the tip is the most important and has strongly effects on the improve appearance and quality of life. The aim of the present study was to evaluate reshaping the tip of the nose by cross-linked hyaluronic acid using Italian technique. METHODS: In a period between November 2019 and 2023, a total of one hundred and forty healthy, 95 females and 45 man patients, were performed with a mean age 44±5 (age range: 31-52 years old) affected by tip of congenital (22) or ageing nose hypotonia (118), and reduced volume that need of an elevation of the nose tip. The anatomic markers have been considered for the anthropometric measurements after the filler rhinoplasty. Two infiltrations were performed, one in the infiltration into the antero-caudal access over the columella produce upward rotation of the tip of the nose and second infiltration into the antero-superior access produce the projection of the tip of the nose. Medical device used in the study was Neofound STRUCT LIDO (LOVE COSMEDICAL srls-Via Toniolo 9, 57022 Castagneto Carducci, ITALY) containing sodium hyaluronate/hyaluronic acid high molecular weight (1.500

The Model of Interstitial Cystitis for Evaluating New Molecular Strategies of Interstitial Regeneration in Humans.

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.

Loss of CFTR Reverses Senescence Hallmarks in SARS-CoV-2 Infected Bronchial Epithelial Cells.

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.

Hyper- and Hypopigmentation in a Subject with Fitzpatrick Skin Phototype VI: A New Treatment Option.

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.

Histological analysis of the dermal and hypodermal layers of the face and correlation with high-frequency 24 MHz ultrasonography and elastosonography.

Knowledge of the structure of the face is of fundamental importance. In fact, the face is treated in many areas of medicine, from dermatology, to maxillofacial surgery, to otorhinolaryngology, to ophthalmology, etc. and anti-aging aesthetic treatments, and those for the resolution of blemishes are on the increase. For ethical reasons it is not possible to take biopsy samples for facial analysis in the aesthetic field. The main aim of this study was to demonstrate that a high-resolution bimodal ultrasound examination, combined with elastosonography, could be a valid tool for pre-treatment morphological evaluation. To achieve this goal, skin samples were taken from the forehead, zygomatic area, nasolabial fold, upper and lower lip from cadavers to histologically characterize their structure. Subsequently, these same areas were evaluated in vivo using conventional B-mode ultrasound with a 24 MHz high-frequency probe, and elastosonography. The data obtained with the different techniques were compared, in order to state that modern ultrasound techniques can provide similar histological information. The analysis showed that the superficial hypodermis presented a different shape and structure in the different areas, with the exception of the areas of the upper and lower lip, which appeared similar. With aging, the forehead and zygomatic area showed a volumetric increase in the superficial hypodermic layer, while the lip showed non-structural changes. The morphology of the nasolabial fold remained unchanged. When it is not possible to perform histological investigations on the face, to understand its characteristics and dynamics, ultrasound with a 24 MHz probe would seem to be the most suitable method, while elastosonography could be a valid method for evaluating the stiffness of the structural components.

The human dermal white adipose tissue (dWAT) morphology: A multimodal imaging approach.

BACKGROUND: Dermal white adipose tissue (dWAT) in humans can be characterized as a relaxed dermal skin compartment consisting of functionally interlinked adipocytes. dWAT is typically discerned both in terms of morphology and function from subcutaneous white adipose tissue (sWAT). In particular in human thigh, the dWAT appears as thin extensions from the adipose panniculus to the dermis, and it is primarily associated with pilosebaceous units, hair follicles, sebaceous glands, and erector pili muscles. In this work, human fat tissue samples obtained post-mortem from the gluteo-femoral region were analyzed focusing on the thin extensions of dWAT named dermal cones. This anatomical region was chosen to deepen the dWAT morphological features of this site which is interesting both for clinical applications and genetical studies. The purpose of this exploratory methodological study was to gain deeper insights into the morphological features of human dWAT through a multimodal imaging approach. METHODS: Optical microscopy, Magnetic Resonance Imaging (MRI) and Scanning Electron Microscopy (SEM), have been employed in this study. The cones' length and their distances were measured on the acquired images for optical microscopy and SEM. The cone's apparent regular distribution in MRI images was evaluated using a mathematical criterion, the conformity ratio, which is the ratio of the mean nearest-neighbor distance to its standard deviation. RESULTS: The imaging techniques revealed white adipocytes forming a layer, referred to as sWAT, with cones measuring nearly 2 mm in size measured on SEM and Optical images (2.1 ± 0.4 mm), with the lower part embedded in the sWAT and the upper part extending into the dermis. The distance between the cones results about 1 mm measured on MRI images and they show an overall semiregular distribution. CONCLUSIONS: MRI images demonstrated an orderly arrangement of cones, and their 3D reconstruction allowed to elucidate the dermal cones' disposition in the tissue sample and a more general comprehensive visualization of the entire fat structure within the dermis.

Innovative Non-Surgical Plastic Technique for Saddle Nose Correction: A Study on 97 Patients.

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.

A pilot study on the efficacy of a seaweed mud application in the treatment of cellulite.

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.

V-EMF therapy: A new painless and completely non-invasive treatment for striae gravidarum.

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.

Glial Response and Neuronal Modulation Induced by Epidural Electrode Implant in the Pilocarpine Mouse Model of Epilepsy.

In animal models of epilepsy, cranial surgery is often required to implant electrodes for electroencephalography (EEG) recording. However, electrode implants can lead to the activation of glial cells and interfere with physiological neuronal activity. In this study, we evaluated the impact of epidural electrode implants in the pilocarpine mouse model of temporal lobe epilepsy. Brain neuroinflammation was assessed 1 and 3 weeks after surgery by cytokines quantification, immunohistochemistry, and western blotting. Moreover, we investigated the effect of pilocarpine, administered two weeks after surgery, on mice mortality rate. The reported results indicate that implanted mice suffer from neuroinflammation, characterized by an early release of pro-inflammatory cytokines, microglia activation, and subsequent astrogliosis, which persists after three weeks. Notably, mice subjected to electrode implants displayed a higher mortality rate following pilocarpine injection 2 weeks after the surgery. Moreover, the analysis of EEGs recorded from implanted mice revealed a high number of single spikes, indicating a possible increased susceptibility to seizures. In conclusion, epidural electrode implant in mice promotes neuroinflammation that could lower the seizure thresholds to pilocarpine and increase the death rate. An improved protocol considering the persistent neuroinflammation induced by electrode implants will address refinement and reduction, two of the 3Rs principles for the ethical use of animals in scientific research.

Gluteal femoral subcutaneous and dermal adipose tissue in female.

BACKGROUND: During the sexual maturation, gluteal femoral adipose tissue is subjected to numerous modifications, not observable in other regions, in particular in women and less in men. Other authors described this region, but they used imaging techniques having lower resolution, than MRI proposed in this study. High resolution imaging techniques might provide important and more detailed information about the anatomy of gluteal femoral region. METHODS: This study has been performed using 7 T-magnetic resonance imaging and ultrastructural analysis in order to provide accurate description of the subcutaneous adipose tissue and dermis of gluteal femoral region. In this study specimens harvested from cadavers and form living patients have been analyzed. RESULTS: The results showed the presence of three layers: superficial, middle, and deep, characterized by different organization of fat lobules. High resolution imaging showed the adipose papilla that originates from dermis and protrude in subcutaneous adipose tissue. Adipose papilla is characterized by a peculiar morphology with a basement, a neck and a head and these elements represent the functional subunits of adipose papilla. Moreover, ultrastructural study evidenced the relationship between adipocytes and sweat glands, regulated by lipid vesicles. CONCLUSIONS: This study provides important information about subcutaneous and dermal fat anatomy of gluteal femoral region, improving the past knowledge, and move toward a better understanding of the cellulite physiopathology.

Decreased apoptotic priming and loss of BCL-2 dependence are functional hallmarks of Richter's syndrome.

Richter's syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into a high-grade B-cell malignancy. Molecular and functional studies have pointed out that CLL cells are close to the apoptotic threshold and dependent on BCL-2 for survival. However, it remains undefined how evasion from apoptosis evolves during disease transformation. Here, we employed functional and static approaches to compare the regulation of mitochondrial apoptosis in CLL and RS. BH3 profiling of 17 CLL and 9 RS samples demonstrated that RS cells had reduced apoptotic priming and lower BCL-2 dependence than CLL cells. While a subset of RS was dependent on alternative anti-apoptotic proteins and was sensitive to specific BH3 mimetics, other RS cases harbored no specific anti-apoptotic addiction. Transcriptomics of paired CLL/RS samples revealed downregulation of pro-apoptotic sensitizers during disease transformation. Albeit expressed, effector and activator members were less likely to colocalize with mitochondria in RS compared to CLL. Electron microscopy highlighted reduced cristae width in RS mitochondria, a condition further promoting apoptosis resistance. Collectively, our data suggest that RS cells evolve multiple mechanisms that lower the apoptotic priming and shift the anti-apoptotic dependencies away from BCL-2, making direct targeting of mitochondrial apoptosis more challenging after disease transformation.