The Association of Telangiectasias with Other Peripheral Vascular Lesions of Systemic Sclerosis.

Purpose: Systemic sclerosis (SSc) is a relatively rare collagenosis manifested as microvasculopathy, excessive cutaneous and visceral fibrosis in a background of autoimmune alteration. Autoimmune vasculopathy in SSc occurs early and begins with endothelial cell activation followed by blood vessel intimal proliferation in a context of defective angiogenesis. The alteration of peripheral micro and macrocirculation in SSc is evident through vascular lesions, such as Raynaud's phenomenon, telangiectasias, acrocyanosis, digital ulcers, gangrene, peripheral pulse deficiency. Our paper details the results of the study on the association between telangiectasias and other types of immune-mediated peripheral vascular lesions that can be identified in SSc. The presence of these peripheral vascular lesions can provide information about the magnitude of the peripheral vasculopathy. Patients and Methods: A total of 37 patients diagnosed with SSc, recruited from a university clinic in Bucharest between February 2019 and March 2020, were enrolled in an observational study. We evaluated the presence of telangiectasias, as a stigma of autoimmune microvasculopathy, and their association with other immune-mediated peripheral vascular lesions that may be present in SSc. Results: The presence of telangiectasias was identified in the absence, but especially in the presence of acrocyanosis and digital ulcerations, and patients with peripheral pulse deficiency almost always had telangiectasias. Less than a quarter of the patients with digital ulcers progressed unfavorably to gangrene, and only one required amputation, telangiectasias being present not only in the patient with amputation but in all patients with gangrene. Conclusion: We appreciate that telangiectasias may be the clinical expression of peripheral vasculopathy characteristic of SSc, they can often be present in association with other peripheral vascular lesions and may represent a valuable indicator for the gangrene risk of digital ulcerations in SSc.

Immunologic and nonimmunologic sclerodermal skin conditions - review.

Scleroderma-like cutaneous lesions have been found in many pathological conditions and they have the clinical appearance of sclerotic or scleroatrophic lesions. Affected skin biopsies described histopathological changes similar to those of scleroderma located strictly on the skin or those of systemic sclerosis. These skin lesions can be found in inflammatory diseases with autoimmune substrate (generalized morphea, chronic graft versus host disease, eosinophilic fasciitis), tissue storage diseases (scleredema, scleromyxedema, nephrogenyc systemic fibrosis, systemic amyloidosis), metabolic diseases (porphyrya cutanea tarda, phenylketonuria, hypothyroidism, scleredema diabeticorum), progeroid syndromes. Given the multiple etiologies of sclerodermal lesions, a correct differential diagnosis is necessary to establish the appropriate treatment.

Mental health at different stages of cancer survival: a natural language processing study of Reddit posts.

Introduction: The purpose of this study was to use text-based social media content analysis from cancer-specific subreddits to evaluate depression and anxiety-loaded content. Natural language processing, automatic, and lexicon-based methods were employed to perform sentiment analysis and identify depression and anxiety-loaded content. Methods: Data was collected from 187 Reddit users who had received a cancer diagnosis, were currently undergoing treatment, or had completed treatment. Participants were split according to survivorship status into short-term, transition, and long-term cancer survivors. A total of 72524 posts were analyzed across the three cancer survivor groups. Results: The results showed that short-term cancer survivors had significantly more depression-loaded posts and more anxiety-loaded words than long-term survivors, with no significant differences relative to the transition period. The topic analysis showed that long-term survivors, more than other stages of survivorship, have resources to share their experiences with suicidal ideation and mental health issues while providing support to their survivor community. Discussion: The results indicate that Reddit texts seem to be an indicator of when the stressor is active and mental health issues are triggered. This sets the stage for Reddit to become a platform for screening and first-hand intervention delivery. Special attention should be dedicated to short-term survivors.

New Methacrylated Biopolymer-Based Hydrogels as Localized Drug Delivery Systems in Skin Cancer Therapy.

The aim of the present work was to obtain drug-loaded hydrogels based on combinations of dextran, chitosan/gelatin/xanthan, and poly (acrylamide) as a sustained and controlled release vehicle of Doxorubicin, a drug used in skin cancer therapy that is associated with severe side effects. Hydrogels for use as 3D hydrophilic networks with good manipulation characteristics were produced using methacrylated biopolymer derivatives and the methacrylate group's polymerization with synthetic monomers in the presence of a photo-initiator, under UV light stimulation (365 nm). Transformed infrared spectroscopy analysis (FT-IR) confirmed the hydrogels' network structure (natural-synthetic composition and photocrosslinking), while scanning electron microscopy (SEM) analysis confirmed the microporous morphology. The hydrogels are swellable in simulated biological fluids and the material's morphology regulates the swelling properties: the maximum swelling degree was obtained for dextran-chitosan-based hydrogels because of their higher porosity and pore distribution. The hydrogels are bioadhesive on a biological simulating membrane, and values for the force of detachment and work of adhesion are recommended for applications on skin tissue. The Doxorubicin was loaded into the hydrogels and the drug was released by diffusion for all the resulting hydrogels, with small contributions from the hydrogel networks' relaxation. Doxorubicin-loaded hydrogels are efficient on keratinocytes tumor cells, the sustained released drug interrupting the cells' division and inducing cell apoptosis; we recommend the obtained materials for the topical treatment of cutaneous squamous cell carcinoma.

Improving flexor tendon gliding by using the combination of carboxymethylcellulose-polyethylene oxide on murine model.

The current approach to flexor tendon injuries is complex and is no longer limited to suturing techniques. Strategies for improving hand function currently include rehabilitation protocols, appropriate suturing materials and techniques, changing the gliding surface by using lubricants and providing growth factors. One product, originally used in spinal surgery, has been shown to be effective in preventing postoperative adhesions. It is a combination of carboxymethylcellulose and polyethylene oxide-Dynavisc® (FzioMed, Inc.). The aim of the present study was to test the effect of Dynavisc® on acute injuries of the intrasynovial flexor tendons in the prevention of postoperative adhesions and the improvement of functional results. The study was performed on 20 Wistar rats distributed in two groups. The control group, represented by 10 rats, in which after the reconstruction of the flexor tendon, the peritendinous area was injected with saline solution and the study group, in which the peritendinous area was injected with a single administration of the lubricating gel, Dynavisc® (carboxymethylcellulose and polyethylene oxide). At 4 and 12 weeks, the rats were sacrificed and tissue biopsy consisted of tendon fragments and adjacent tissue. The evaluation of the results was performed by measuring the adhesion score and observing histological parameters. The presence of important adhesions was found in the control group compared with the group treated with Dynavisc®, where a supple and smooth tendon, with significantly fewer adhesions were found. The differences between the two groups were significant, thus indicating the efficiency of the lubricant in preventing adhesions. This study supported the important role of Dynavisc® in the regeneration of the tendon and the peritendinous structures, by limiting aberrant fibrous proliferation in the regeneration process and helping to build a peritendinous space.

Contamination fear in the time of the COVID-19 pandemic: A moderated mediation quasi-experimental model of the effect of disgust on outgroup bias towards diaspora.

Disgust sensitivity plays a key role in generating and maintaining outgroup biases. To test our hypotheses, we used a quasi-experimental between-subjects design, in which participants were randomly assigned to a disgust induction condition (N = 102) or a non-induction neutral group (N = 92). The induction scenario featured the return of the diaspora to their home country due to COVID-19 concerns. In one scenario, the diaspora lied about the country they arrived from, and in the other, there was no moral transgression. We hypothesized that the effect of disgust sensitivity on dehumanization and aggressive tendencies passed through contamination fear and the moderated mediation model indicated that this indirect effect was stronger for participants in the disgust-induction than in the non-induction group. This effect was found for biological dehumanization and passive aggression outcomes, both related to outgroup bias. Consistent with the role of disgust as a disease-avoidance mechanism, our results suggest that disgust could facilitate stronger outgroup bias in the context of a high health threat, such as the COVID-19 pandemic.

Deciphering metformin action in obese mice: A critical re-evaluation of established protocols.

BACKGROUND AND PURPOSE: Despite extensive efforts and a plethora of suggested targets and pathways, the mechanism via which metformin lowers blood glucose remains obscure. Obstacles that hamper progress in understanding metformin action include unexplained discrepancies between preclinical models and patients. PROCEDURES: We treated obese male C57BL/6J mice fed high fat diet with metformin provided in the form of a single dose, daily intraperitoneal injections, admixture to drinking water, or continuous infusion via intraperitoneal minipumps. RESULTS: The results suggest several superimposed components, via which metformin acts on blood glucose. These include (i) marked glucose lowering shortly after dosing, which fades rapidly with the decrease in metformin concentrations in plasma and liver, but could, at least to a major extent, rely on the mechanism also accounting for metformin's therapeutic action in humans; (ii) indirect action via reduced weight gain, which might be responsible for glucose lowering observed in many previous rodent studies; and (iii) deterioration of glucose homeostasis by prolonged treatment that can be unmasked by avoidance of dosing shortly before measuring blood glucose in combination with exclusion of weight-related actions via restricted feeding of the control mice. CONCLUSIONS: Our work raises the question whether elucidation of metformin's anti-diabetic mechanism(s) in rodent experiments may in the past have been hampered by failure to mimic clinical circumstances, as caused by insufficient consideration of pharmacokinetics and multiplicity of involved actions.

Adipocyte STAT5 deficiency does not affect blood glucose homeostasis in obese mice.

The aim of this study was to investigate whether the lack of signal transducer and activator of transcription 5 (STAT5) in mature adipocytes of obese mice (Stat5Adipoq mice) improves glucose and lipid metabolism as previously observed in lean mice. Male Stat5Adipoq mice and their wild type (WT) littermates were fed high-fat diet (HFD). Effects of adipocyte STAT5 deficiency on adiposity as well as on glucose and lipid metabolism were determined under ad libitum feeding and after weight loss induced by calorie restriction. Compared to WT mice, obese Stat5Adipoq mice showed modestly accelerated weight gain and blunted depletion of fat stores under calorie restriction (reduction in % body fat after 3 weeks: WT, -9.3±1.1, vs Stat5Adipoq, -5.9±0.8, p = 0.04). No differences were observed between Stat5Adipoq and WT mice with regard to parameters of glucose and lipid metabolism including basal glycaemia, glucose tolerance, and plasma triglycerides. In conclusion, STAT5 deficiency in the adipocyte of HFD-fed obese mice was associated with increased fat accumulation. In contrast to previous findings in lean mice, however, lipid accumulation was not associated with any improvement in glucose and lipid metabolism. Our results do not support adipocyte STAT5 as a promising target for the treatment of obesity-associated metabolic derangements.

Deep Learning Application for Analyzing of Constituents and Their Correlations in the Interpretations of Medical Images.

The need for time and attention, given by the doctor to the patient, due to the increased volume of medical data to be interpreted and filtered for diagnostic and therapeutic purposes has encouraged the development of the option to support, constructively and effectively, deep learning models. Deep learning (DL) has experienced an exponential development in recent years, with a major impact on interpretations of the medical image. This has influenced the development, diversification and increase of the quality of scientific data, the development of knowledge construction methods and the improvement of DL models used in medical applications. All research papers focus on description, highlighting, classification of one of the constituent elements of deep learning models (DL), used in the interpretation of medical images and do not provide a unified picture of the importance and impact of each constituent in the performance of DL models. The novelty in our paper consists primarily in the unitary approach, of the constituent elements of DL models, namely, data, tools used by DL architectures or specifically constructed DL architecture combinations and highlighting their "key" features, for completion of tasks in current applications in the interpretation of medical images. The use of "key" characteristics specific to each constituent of DL models and the correct determination of their correlations, may be the subject of future research, with the aim of increasing the performance of DL models in the interpretation of medical images.

Down-regulation of A20 promotes immune escape of lung adenocarcinomas.

Inflammation is a well-known driver of lung tumorigenesis. One strategy by which tumor cells escape tight homeostatic control is by decreasing the expression of the potent anti-inflammatory protein tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20. We observed that tumor cell intrinsic loss of A20 markedly enhanced lung tumorigenesis and was associated with reduced CD8+ T cell-mediated immune surveillance in patients with lung cancer and in mouse models. In mice, we observed that this effect was completely dependent on increased cellular sensitivity to interferon-γ (IFN-γ) signaling by aberrant activation of TANK-binding kinase 1 (TBK1) and increased downstream expression and activation of signal transducer and activator of transcription 1 (STAT1). Interrupting this autocrine feed forward loop by knocking out IFN-α/ß receptor completely restored infiltration of cytotoxic T cells and rescued loss of A20 depending tumorigenesis. Downstream of STAT1, programmed death ligand 1 (PD-L1) was highly expressed in A20 knockout lung tumors. Accordingly, immune checkpoint blockade (ICB) treatment was highly efficient in mice harboring A20-deficient lung tumors. Furthermore, an A20 loss-of-function gene expression signature positively correlated with survival of melanoma patients treated with anti-programmed cell death protein 1. Together, we have identified A20 as a master immune checkpoint regulating the TBK1-STAT1-PD-L1 axis that may be exploited to improve ICB therapy in patients with lung adenocarcinoma.

Biomacromolecular-based ionic-covalent hydrogels for cell encapsulation: The atelocollagen - Oxidized polysaccharides couples.

Mixed crosslinked networks of ionic-covalent entanglement type were prepared starting from ternary mixtures of atelocollagen (aK; as fibrillary matrix generator), sodium hyaluronate (NaHyal; a microfibrillation assistant), and oxidized polysaccharides (OxPolys; as both cross-linkers and matrix fillers), and were tested as hydrogels for eukaryotic cell encapsulation. Either oxidized gellan (GellOx) or pullulan (PullOx) were used. An original procedure and optimal hydrogel recipes were developed to encapsulate fibroblasts and adipose-derived stem cells, while preserving their viability and proliferative ability during ex vivo temporarily storage. Physical-chemical, rheological, and biocompatibility properties of the prepared hydrogels were compared against the classic alginate hydrogel used for cell encapsulation. A larger range of material characteristics (from lax to stiff) and better laboratory maneuverability were demonstrated, which permit to design appropriate compositions for particular cell types. All hydrogels undergo fast liquefaction at temperatures between 42 and 50°C, permitting the cell release after a short innocuous thermal shock.

Atelocollagen-based Hydrogels Crosslinked with Oxidised Polysaccharides as Cell Encapsulation Matrix for Engineered Bioactive Stromal Tissue.

Tissue stroma is responsible for extracellular matrix (ECM) formation and secretion of factors that coordinate the behaviour of the surrounding cells through the microenvironment created. It's inability to spontaneously regenerate makes it a good candidate for research studies such as testing various tissue engineered products capable of replacing the stroma in order to assure normal tissue regeneration and function. In this study, a bioactive stroma was obtained considering two main components: 1) the artificial ECM formed using atelocollagen-oxidized polysaccharides hydrogels in which the polysaccharide compound (oxidised gellan or pullulan) has the role of crosslinker and 2) encapsulated stromal cells (dermal fibroblasts, ovarian theca-interstitial and granulosa cells). The cell-hosting ability of the hydrogels is demonstrated by a good diffusion of globular proteins (albumin) while the fibrillar morphology proves to be optimal for cell adhesion. These structural properties and cytocompatibility of the components maintain good cell viability and cell encapsulation for more than 12 days. Nevertheless, the results indicate some differences favouring the gellan crosslinked hydrogels. Ovarian stromal cells functionality was maintained as indicated by hormone secretion, confirming cell-cell signalling in encapsulated and co-culture conditions. In vivo implantation shows the regenerative potential of the cell-populated hydrogels as they are integrated into the natural tissue. The possibility of cryopreserving the hydrogel-cell system, while maintaining both cell viability and hydrogel structural integrity underlines the potential of these ready-to-use hydrogels as bioactive stroma for multipurpose tissue regeneration.