Inflammatory Connective Tissue Research Articles

Histological evaluation of gingival enlargement response to oral folic acid administration in rabbit

Aims of the study: to clarify the clinical and histological evaluation of oral folic acid effect on reduction of gingival enlargement. Materials and methods: The study was carried out in the collage of dentistry /university of Mosul on twelve white newzeland male rabbit with gingival enlargement weight between (900 g±1.250g). six rabbit considered as control group and the other six rabbit considered as treated group which taking 15 mg orally folic acid once daily for about 14 days then depth of gingival sulcus evaluated clinically by periodontal` probe and euthaniused for histological examination. Result: Clinically: after 14 days of drug administration, there is a high clinical differences between two group (mean +- SD), control group have (3-5mm) of gingival enlargement and experimental group have (1-3 mm) of gingival enlargement. Histological finding show significant differences in the form of gingival sulcus depth and inflammatory cell infiltration and connective tissue in control group and experimental group. Conclusion: the effect of oral administration of folic acid have higher evaluation on reducing the gingival enlargement in rabbit

OA24 Airway obstruction in an adolescent: relapsing polychondritis

OA24 Airway obstruction in an adolescent: relapsing polychondritis

Foot and Ankle Conventional Radiography in Juvenile Idiopathic Arthritis: Does It Still Matter?

Objectives:The aim of this study was to evaluate the residual value of Conventional Radiography in children with arthralgia clinically suspected of Juvenile Idiopathic Arthritis (JIA).Materials and Methods:Three hundred seventy-two patients aged 1–18 years suspected of JIA were retrospectively reviewed. All patients had foot and ankle plain films performed in standard two projections: ankle in antero-posterior and lateral, and foot in antero-posterior and oblique. The cohort was divided into two groups: patients with confirmed JIA and non-JIA control group of children with foot and ankle arthralgia without diagnosis of inflammatory connective tissue disease. Radiographic findings in both groups were compared.Results:In 40% of JIA and 70% of non-JIA patients radiographs were normal. All radiographic findings were significantly more common in JIA than in non-JIA group (p = 0.000). Soft tissue swelling was the most frequent abnormality found in JIA patients (31, 51%) and only in 2.41% of non-JIA patients (p = 0.000). Osteoporosis and joint space narrowing were also significantly more common in JIA group (p = 0.000). The majority of imaging findings in non-JIA group were non-inflammatory abnormalities.Conclusion:Conventional radiography is an important tool in differential diagnosis of arthralgia of unknown etiology, as soft tissue swelling, osteoporosis and joint space narrowing are significantly more common in JIA patients as compared with patients without the diagnosis of inflammatory connective tissue disease. However, in case of high clinical suspicion of JIA and normal radiography, we recommend subsequent ultrasound (US) and/or MRI to allow early treatment.

The Role of Leptin in Systemic Lupus Erythematosus: Is It Still a Mystery?

Systemic lupus erythematosus (SLE) is a chronic inflammatory connective tissue disease with varying clinical manifestations. Recent studies have proposed that leptin may be related to SLE development. This study aims to assess current information regarding the relationship between leptin and SLE. A systematic search was done using PubMed, Google Scholar, ScienceDirect, Epistemonikos, and Cochrane Library databases. Studies published in the English language in the last 10 years were selected based on predefined eligibility criteria. The quality of the studies was evaluated using the Newcastle-Ottawa Scale and the Assessment of Multiple Systematic Reviews 2 tool.A total of 12 studies were included in this systematic review. These included systematic reviews/meta-analyses, cross-sectional studies, and case-control studies. Based on the findings of this review, we conclude thatleptin is significantly elevated in SLE patients; however, it does not seem to correlate with disease activity. The exact mechanism of leptin in the pathogenesis of the disease remains unknown and further research is needed regarding this aspect.

Glycolysis in Innate Immune Cells Contributes to Autoimmunity.

Autoimmune diseases (AIDs) refer to connective tissue inflammation caused by aberrant autoantibodies resulting from dysfunctional immune surveillance. Most of the current treatments for AIDs use non-selective immunosuppressive agents. Although these therapies successfully control the disease process, patients experience significant side effects, particularly an increased risk of infection. There is a great need to study the pathogenesis of AIDs to facilitate the development of selective inhibitors for inflammatory signaling to overcome the limitations of traditional therapies. Immune cells alter their predominant metabolic profile from mitochondrial respiration to glycolysis in AIDs. This metabolic reprogramming, known to occur in adaptive immune cells, i.e., B and T lymphocytes, is critical to the pathogenesis of connective tissue inflammation. At the cellular level, this metabolic switch involves multiple signaling molecules, including serine–threonine protein kinase, mammalian target of rapamycin, and phosphoinositide 3-kinase. Although glycolysis is less efficient than mitochondrial respiration in terms of ATP production, immune cells can promote disease progression by enhancing glycolysis to satisfy cellular functions. Recent studies have shown that active glycolytic metabolism may also account for the cellular physiology of innate immune cells in AIDs. However, the mechanism by which glycolysis affects innate immunity and participates in the pathogenesis of AIDs remains to be elucidated. Therefore, we reviewed the molecular mechanisms, including key enzymes, signaling pathways, and inflammatory factors, that could explain the relationship between glycolysis and the pro-inflammatory phenotype of innate immune cells such as neutrophils, macrophages, and dendritic cells. Additionally, we summarize the impact of glycolysis on the pathophysiological processes of AIDs, including systemic lupus erythematosus, rheumatoid arthritis, vasculitis, and ankylosing spondylitis, and discuss potential therapeutic targets. The discovery that immune cell metabolism characterized by glycolysis may regulate inflammation broadens the avenues for treating AIDs by modulating immune cell metabolism.

Autologous hematopoietic stem cell transplantation promotes connective tissue remodeling in systemic sclerosis patients

BackgroundAutologous hematopoietic stem cell transplantation (AHSCT) treats patients with severe and progressive systemic sclerosis (SSc). However, basic mechanisms associated with the therapeutic efficacy of the procedure are not entirely understood. We aimed to evaluate how AHSCT affects skin fibrosis in SSc patients.MethodsClinical data, serum, and skin samples from 39 SSc patients who underwent AHSCT were retrospectively evaluated. Skin biopsies were analyzed by immunohistochemistry with anti-MMP-1, -MMP-2, -MMP-3, -MMP-9, -TIMP-1, -α-SMA, -TGF-β, and -NF-κB p65 antibodies, and stained with hematoxylin and eosin and picrosirius red to assess skin thickness and collagen density, respectively. Serum samples were evaluated by Multiplex Assay for COL1A1, COL4A1, FGF-1, MMP-1, MMP-3, MMP-12, MMP-13, PDGF-AA, PDGF-BB, S100A9, and TIMP-1 levels and compared to healthy controls.ResultsAfter AHSCT, SSc patients showed clinical improvement in skin involvement, assessed by modified Rodnan’s skin score (mRSS). Histologically, collagen density and skin thickness decreased after AHSCT. Immunohistochemical analyses showed increased expression of MMP-2, MMP-3, MMP-9, and TIMP-1 after AHSCT, whereas expression of NF-κB p65 decreased. At baseline, serum levels of COL4A1 and S100A9 were higher than in healthy controls. Serum levels of S100A9 normalized after AHCST in SSc patients compared to controls. Serum levels of PDGF-AA, PDGF-BB, TIMP-1, and MMP-1 decreased, while COL1A1 increased after AHSCT in SSc patients. No changes were detected in MMP-3, MMP-12, MMP-13, and FGF-1 serum levels after AHSCT.ConclusionsOur results suggest that the therapeutic effects of AHSCT on skin fibrosis are related to changes in molecules associated with connective tissue maintenance and inflammation in SSc.

P021 Development of a Rheumatology Hot Clinic in the Midst of a Pandemic

Background/AimsThe COVID-19 pandemic has had a significant impact on emergency and scheduled care, affecting both inpatient and outpatient services for all specialities, including Rheumatology. During the first pandemic peak, rheumatology outpatient clinics all became virtual (i.e. telephone or video), except for a single emergency clinic per week. However, this face-to-face clinic, quickly became oversaturated resulting in a waiting list extending above 4 weeks for our patients.MethodsIn the lead-up to the second COVID-19 peak during the winter, we developed a novel, urgent, hot Rheumatology Clinic within our Ambulatory Emergency Care (AEC) department. This whole-day weekly clinic was delivered by a Rheumatology registrar, with consultant support. Its purpose was to provide a service for patients who did not require hospitalisation but required urgent face-to-face Rheumatology speciality review that could not wait for an outpatient appointment. Referrals came from General Practice, Urgent Care (i.e. Emergency Care, Acute Medicine and AEC) and from the Rheumatology department. Pathologies reviewed included vasculitides, inflammatory arthritis and inflammatory connective tissue diseases. The clinic facilitated for patients with suspected new diagnoses or flares of established rheumatological diseases. Furthermore, patients could also undergo urgent joint and soft tissue procedures. All referrals were directed to the Rheumatology registrar to triage. Because of the success of the clinic, it continued beyond the second peak with data gathered from its inception.ResultsData was collected between November 2020 and June 2021, covering 23 hot clinics. A total of 118 patients were reviewed during this period. The highest number of referrals occurred during the second peak of the pandemic (38 patients over seven clinics compared to 48 patients over ten clinics post-peak). The majority of referrals were from Rheumatology directly (70%) compared with Urgent Care (14%) and General Practice (12%). Most (60%) were seen within 7-days of referral; a further 27% were seen within 7- 14 days. The main reasons for review delays beyond seven-days were lack of available clinic (46%) or lack of space (29%). The most common disease encountered was a chronic inflammatory arthropathy (48 patients).ConclusionThe service has generated positive feedback from all patients. Furthermore, this clinic has benefited both Rheumatology and AEC. Firstly, it ensured timely face-to-face reviews of patients requiring urgent Rheumatology assessments. Secondly, it eased pressure on the Rheumatology department, particularly the outpatient emergency clinic. Thirdly, it ensured that the Rheumatology registrar continued to have Rheumatology training opportunities, particularly when redeployed during the Winter wave on other days of the week. Fourthly, the AEC department have had easier access to Rheumatology reviews. Finally, it has empowered the registrar to manage their own workload and organise the clinic enhancing management and leadership experience. The success of the clinic has resulted in its ongoing continuation.Disclosure A. Khan: None. C. Murdoch: None. I. Wamuo: None.

Subdermal Silicone and Collagen Injection Effect on the Skin of Rats (Rattus norvegicus) on the Third Day After Injection

Collagen and silicone are substances commonly used as dermal filler in a number of beauty procedures. However, sometimes these chemicals cause unwanted side effects on the skin. The purpose of this research is to analyse the effect of collagen and silicone subdermal injection on rat skin as a model for human skin. Materials in this research are 9 Wistar rats (Rattus norvegicus) divided into three groups with a number of 3 rats in each group. The first control group (K) is not given any injections, while KI and KII are injected with 0,1 ml collagen and 0,1 ml silicone respectively. On the third day, all groups are observed for macroscopic changes. Skin samples are taken by necropsy and are made into slides using HE stain. All procedures done are approved by the ethics commission of LLPT, UGM, Yogyakarta with the certificate number 00024/04/LPPT/V/2019. The slides are observed under a microscope with 20x and 40x magnification. Any microscopic changes are noted, also epidermis and dermis lengths are measured. Mild hyperkeratosis, inflammation and proliferation of connective tissue are found. The measurements of the epidermis and dermis are analysed using T-test independent method in the program Statistical Product and Service Solution (SPSS). The mean length of the epidermis is a little thicker than normal but is not significant (P>0,05). The results of this research show that the subdermal injection of 0,1 ml collagen and 0,1 ml silicone on rats do not cause significant macroscopic or microscopic changes.

Intraosseous Benign Fibrous Histiocytoma of the Mandible

<h3>Introduction</h3> Fibrous histiocytomas are a diverse group of tumors that exhibit fibroblastic and histiocytic differentiation and are considered to be a true neoplasm. Intrabony fibrous histiocytomas of the jaws are rare, with most cases being reported in the femur, tibia, pelvis and occasionally the skull bones. <h3>Material and Methods</h3> This report describes a case of 69 year old male patient who presented with pain in the area of tooth #18 (mandibular left second molar) and an endo-perio lesion that perforated through the cortical bone which appeared to be multilocular on radiographs. Clinically, there was a buccal swelling and when the buccal bifurcation was probed, a 10mm depth was revealed with a purulent exudate emanating from the pocket. The bridge was sectioned at the junction of #19 and 20 pontic followed by extraction of tooth #18. Reflection of the mucosa revealed a large bony lesion destroying the buccal plate of bone in the area of teeth #18 and 19. The purulent material was primarily associated with the tooth #18 and not the overall lesion. The majority of the lesion was enucleated and removed. <h3>Results</h3> Histopathological examination revealed fragments of mildly inflamed connective tissue that demonstrated a focus of spindle or mesenchymal cells proliferating in a whorling or storiform pattern. The tissue contained large scattered deposits of mineralized material and fragments of vital bone. Immunohistochemical stains for Desmin, SMA, CD34 and factor XIIIa were negative while diffusely positive for CD68. The positivity for CD68 demonstrated that the lesion was composed of histiocytic cells. <h3>Conclusions</h3> Benign fibrous histiocytomas of the soft tissues are well recognized entities, the rare intra-bony counterpart shares clinical, radiographic and histological features with odontogenic tumors, non-ossifying fibromas, osteoblastomas and fibrous dysplasia, and therefore should be considered in the differential diagnosis of these lesions.

Facile synthesis and characterization of Au nanoparticles-loaded kaolin mediated by Thymbra spicata extract and its application on bone regeneration in a rat calvaria defect model and screening system

The current work demonstrates the fabrication of kaolin supported Au nanoparticles (Au NPs-kaolin) mediated by Thymbra spicata extract as green reductant and capping agent without any toxic reagent. Physicochemical characteristics of the said nanocomposite were elucidated by field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction and inductively coupled plasma techniques. The figures of the TEM display the black dots signifying Au NPs being dispersed over the kaolin surface. Size of spherical Au NPs are around 10–15 nm. In the in vivo, we established a rat calvaria defect model using a combination of collagen scaffold and nanoparticle. The experimental group was divided into three classifications: control, collagen matrix and nanoparticle with collagen. Histological analyses showed that nanoparticle increased bone formation activity when used in conjunction with collagen matrix. In the nanoparticle group, grafted materials were still present until 12 weeks after treatment, as evidenced by foreign body reactions showing multinucleated giant cells in chronic inflammatory vascular connective tissue. Other results revealed that the nanoparticle increased bone formation activity when used with collagen matrix. All groups showed almost the same histological findings until 7 weeks. In the experimental groups, new bone formation activity was found continuously up to 12 weeks.

Acute Exacerbation of Rheumatoid Arthritis Misdiagnosed as COVID-19: A Case Report

BackgroundRheumatoid arthritis (RA) is a systemic inflammatory connective tissue disease that affects 1–2% of the population worldwide. Pulmonary manifestations including interstitial lung disease (ILD), airway disease, pleural and vascular disease can be seen in up to 30–40% of patients with RA, which are recognized as the second most frequent cause of death in RA patients. The simultaneous occurrence of COVID-19 in RA patients with or without ILD, and the similarities and differences between RA-related ILD and COVID-19 lung findings have been reported in the literature. However, there was no reported case on differentiation of clinical findings of a patient with RA exacerbation causing a new diagnosis of ILD during the pandemic conditions.Case PresentationHere, we presented a patient with RA who was misdiagnosed as COVID-19 twice due to non-specific respiratory symptoms and ground-glass opacities observed in high-resolution CT. The misdiagnosis led to a delayed diagnosis of ILD and prolonged pulmonary symptoms.DiscussionClinicians must critically review patients throughout the diagnostic workup by thinking other diseases besides COVID-19, particularly in the absence of a confirmatory result. The link between ILD or ILD exacerbation and COVID-19 remains to be determined. While research continues in the field, it is important to consider the importance of COVID-19 in cases of ILD exacerbation, and vice versa.ConclusionDistinguishing lung imaging findings of COVID-19 from ILD is a major concern. Even though the primary manifestation of COVID-19 consists of respiratory symptoms, clinicians should be vigilant for other common conditions having the same symptoms. Clinicians should carefully distinguish a differential diagnosis between COVID-19 and a flare of rheumatic disease.

Vitamin D status of patients with systemic inflammatory connective tissue diseases: a cross-sectional study

Background. In addition to regulating mineral metabolism and bone metabolism, vitamin D is important for supporting structure and other types of connective tissue. Studies have shown the role of vitamin D deficiency in the pathogenesis of systemic inflammatory diseases of the connective tissue, autoimmune diseases. The results of studying this problem in countries with different geographic locations are also of interest.Aim. Comparative assessment of vitamin D status of patients with systemic inflammatory diseases of the connective tissue and patients without rheumatic diseases.Materials and methods. This cross-sectional observational study analyzed the vitamin D supply of the following groups: patients with systemic inflammatory diseases of the connective tissue who do not take vitamin D preparations, patients with systemic inflammatory diseases of the connective tissue who take vitamin D preparations, and «conditionally healthy» individuals, without complaints, examined in the same period comparable in gender and age with the patients of the main group. The vitamin D supply of the studied patients was determined by the level of the content of the vitamin D metabolite calcidiol in the blood serum 25 (OH) D. Study period: January 2019 to December 2020.Results. The data of 625 patients who applied to the Osteoporosis Prevention and Treatment Center for the specified period were analyzed. Among the patients of the main group who did not take vitamin D preparations, a deficiency was revealed in 54.7% of the examined, the optimal provision in 11.2%. The median serum 25 (OH) D concentration was in the range of 19.0 ng / ml deficiency. The study participants belonging to the comparison group had a deficit in 44.1% of cases and an optimal provision in 21.5%. The study group of the main group receiving vitamin D preparations had the maximum number of individuals with the optimal status – 37.0%, while a significant part of the examined had a deficit of varying severity – 29.1%. In addition, this group was characterized by the highest median serum metabolite 25 (OH) D – 26.0 ng / ml.Conclusion. A comparative analysis of the D-vitamin status of patients with systemic inflammatory diseases of the connective tissue and «conditionally healthy» individuals without complaints was carried out, which made it possible to establish differences in the provision depending on the existing disease, as well as depending on the therapy with vitamin D preparations. a lower supply of vitamin D than control group «healthy» individuals. In the case of receiving vitamin subsidies, the provision with it in the group of patients was statistically significantly higher, both in comparison with patients who did not take the vitamin, and in comparison, with individuals from the comparison group.

Experimental investigation of animals survival adequacy and efficacy in case of their soft tissues gunshot wounds using the thermometry technique

The problem of gunshot wounds treatment is one of the urgent and incompletely resolved issues of modern surgery. Diagnosis of gunshot wounds is currently not efficient enough. There was a need to improve the content and scope of medical care with the possibility of strengthening its diagnostic chain. The aim of the work is to substantiate experimentally the feasibility and effectiveness of using diagnostic infrared thermometry in gunshot wounds of the soft tissues of the extremities. Experimental studies were performed under the chronic experimental conditions on Shinshilla breed rabbits which were subjected to gunshot wounds followed by laboratory, morphological and functional examination for 5 days. The animals were divided into 3 groups depending on the type of gunshot wound that was inflicted. The animals were removed from the experiment by the introduction of chloroethyl anesthesia on the 1st, 3rd and 5th days, after which the soft tissues with the capsule surrounding the fragment were subjected to histological and electron microscopic examination. On the 1st day of the study, a significant decrease in the diameter of the blood vessels of the affected area was determined in the group of animals that were subject to injury with firearms and metal fragments from the explosion of a grenade and an improvised explosive device. It was in these groups that the highest mortality rate was registered. Under the specified conditions of injury to the limbs of animals, as well as when injured by a pneumatic weapon with a temperature of fragments of 100 oC, pronounced changes in pulse and respiratory rate were noted. In further studies on rabbits on the 3rd and 5th days of the experiment, the actual results did not differ from those obtained 24 hrs after injury. Those rabbits that survived after the reproduction of various gunshot wounds had the greatest value. The results of their thermometric measurements were evaluated in the dynamics of experimental gunshot wounds and revealed the dependence of animal survival after gunshot wounds on the temperature of the limb in the area of the wound.&#x0D; There are the following leading criteria in favor of animals further survival after gunshot wounds - the presence of a perforating vessel in the area surrounding the affected space; the size of the diameter of the vessels in the adjacent area; no hemorrhage in the muscle tissue located near the affected area; comparable with normal data of the functional parameters of the animal's body – heart rate, blood oxygen pressure and respiration; thermometry results. The limb thermometry has the important prognostic value after their gunshot wound in terms of experimental animals survival. The correspondence of high thermometry indexes after a gunshot wound vs the higher risk of an animal death is statistically reliable and, accordingly, insignificant thermometric dynamics throughout the experiment is in favor of a positive outcome after injury. It is extremely important to evaluate thermometry data during the first 24 hours after receiving gunshot wounds, since we found out the maximum validity of this method in the early time intervals. All this, with adequate clinical testing and verification, has the most important medical prospects, aimed primarily at saving time for diagnostic measures and procedures. Thermometry allows to judge the activity and severity of connective tissue inflammation or sclerosis in the lesions of each wound and provides the possibility of clinical application of remote thermography as a non-invasive method of diagnosis and prediction of complications in wounded with gunshot and explosives in various wounds.

Interaction between peritumoral reactivity and histomorphological pattern of lymph node reactivity in oral squamous cell carcinoma: A host immune status indicator.

The invasive tumor front (ITF) of oral squamous cell carcinoma (OSCC) and the reactive changes in regional lymph nodes (RLNs) are believed to carry integral prognostic information about the tumor's invasive capacity and insight into host immune response, respectively. This study aims to evaluate the reactivity patterns of RLNs in relation to the tumor stage, grade and various histopathological parameters at the ITF of primary tumor, in an attempt to elucidate the nature of host-immune response to tumor. Pattern of invasion (POI) using Bryne's criteria, peritumoral inflammation, and status of connective tissue (CT) stroma of 50 OSCC cases, that underwent selective neck dissection were assessed at the ITF. Immunoreactivity patterns in corresponding 450 RLNs were assessed as proposed by Tsakraklides and Ioachim. Further, 97 metastatic lymph nodes (LNs) were evaluated for degree and pattern of tumor invasion. The datasets were subjected to the Chi-square analysis. There was statistically significant association (P = 0.001) of Type III and Type IV POI as well as mild peritumoral inflammation (P = 0.024) with the advanced stages of OSCC as compared to early stages. Significant association was observed between LN reactivity pattern and tumor stage (P = 0.05), with metastatic nodes exhibiting germinal center predominance (97.9%) and lymphocyte predominance (69.1%) largely observed in nonmetastatic nodes. Majority of metastatic nodes showed Grade 3 invasion (54.7%) in the form of large islands (57.7%), whereas two (2.1%) nodes were totally effaced by tumor metastasis. Statistical significance was observed between CT stroma at ITF and degree of tumor invasion in metastatic LN (P = 0.001). POI also showed significant correlation with peritumoral inflammation (P = 0.002), CT stroma (P = 0.02), and LN reactivity pattern (P = 0.03). This study supports the presence of a strong immunological host-tumor relationship.

Mortality related to COVID-19 in patients with rheumatic and musculoskeletal diseases, first wave of the outbreak: a single-center study.

Objectives:The aim of this study was to assess the cause-specific mortality rate related to COVID-19 (CMR) in patients with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 and to analyze the role of the different RMDs in their mortality risk.Methods:An observational longitudinal study was conducted during the first pandemic wave in our center. Patients with the diagnosis of RMDs and COVID-19 were included. Main outcome is the death related to COVID-19. Independent variable – type of RMDs: autoimmune rheumatic diseases (ARD), such as chronic inflammatory arthritis (CIA) and connective tissue diseases (CTD) and non-autoimmune Rheumatic Diseases (non-ARD). Survival techniques were used to estimate the CMR per 1000 patients-month with a 95% confidence interval (CI), and Cox multivariate regression analysis was run to examine the effect of ARD compared to non-ARD on mortality risk adjusted by confounders. Results were expressed by Hazard Ratio (HR) and CI.Results:Overall, 405 patients were included (642.5 patients-month). During the study period, 44 (10.86%) deaths were recorded. CMR was 68.48 (50.96–92.01). After adjusting for confounders, HR of mortality in ARD compared to non-ARD did not achieve statistical significance [HR: 1.15 (0.64–2.07)], neither CTD versus CIA nor CTD versus non-ARD. Age and certain comorbidities which are being diagnosed in March compared to April or May [HR: 2.43 (1.1–5.55)] increased the mortality risk. Glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) dropped from the final model.Conclusion:In patients with RMDs and COVID-19, CMR was 6.8% patients-month. This study shows that mortality risk is higher in males, older patients, and similar between CTD, CIA, and non-ARD. COVID-19 management improved after the first month of pandemic.Plain Language Summaries Mortality related to the outbreak of COVID-19 in patients with rheumatic and musculoskeletal diseases Why was this study done? - To report the COVID-19-specific mortality rate in patients with a variety of RMDs during the first pandemic peak in a tertiary hospital in Madrid and to analyze the role of specific types of ARD and other possible factors in the risk of death related to COVID-19. What did the researchers do? - We performed a retrospective observational study during the first wave of the COVID-19 pandemic in Madrid, Spain. What did the researchers find? - In this study, neither the different diagnoses of RMDs, including CIA, CTD, or non-ARD disease or its treatment were not implicated as a potential risk of death related to COVID-19- In consonance with other studies, RMDs patients and COVID-19, older age, male sex, and certain comorbidities implied more mortality risk- Our data reflect COVID-19 severity in a particular context, time, and population. In times of the absence of COVID-19 vaccine, healthcare, social, and political measures taken to contain the coronavirus outbreak have worked properly. What do the findings mean? - The presence of comorbidities in RMDs patients represents a greater risk than the different types of RMDs themselves, in the development of COVID-19 fatal outcome. It is important to integrate the control of comorbidities in the daily management.

Changes in the cellular composition of the inflammatory infiltrate and connective tissue of the oral mucosa in rats during wound healing using a protective piezoelectric coating

Introduction. Wound healing is a process based on a complex mechanism of intercellular interaction. The aim was to study changes in the oral mucosa cellular composition during wound healing with and without a protective piezoelectric coating. Materials and methods. The study was carried out on 50 Wistar rats divided into four groups: one control group of intact rats and experimental groups 1, 2, and 3. The rats of the experimental groups were subjected to excision of a lip mucous membrane flap with wound formation. In the animals of experimental group 1, the defect was open. In group 2, we used a polymer membrane with copper modification, and in group 3, the membrane was without copper modification. The animals were sacrificed on days 3, 7, and 12 of the study. We used light and electron microscopy to study the qualitative and quantitative changes in the composition of cell populations at the site of the defect. Results. On day 3, there prevailed neutrophilic infiltration in all groups. In groups 2 and 3, we observed a large number of macrophages and fibroblasts that indicated the transition to the next phase of wound healing. On day 7, in group 1, there persisted extensive neutrophilic and macrophage infiltration, whereas, in groups 2 and 3, the signs of inflammation decreased, and wound healing was active. On day 12, in group 1, all values were significantly higher than in the control group and there was damage to the ultrastructure; in groups 2 and 3, all the studied parameters reached the control values. Conclusion. We revealed the patterns of changes in the cellular composition of a wound during its healing. The use of the coating contributed to accelerated wound healing, which was found during the analysis of changes in the composition of cell populations. The closure of the oral mucosa wounds with polymer piezoelectric membranes was proven to have a good effect on tissue repair and was supposed to reduce the risk of postoperative complications. Keywords: wound defect, mucous membrane, oral cavity, piezoelectrics, inflammation, regeneration, scaffolds, dentistry

Diagnostic Value and Clinical Application of Diffusion-Weighted Magnetic Resonance Imaging for Female Pelvic Lesions.

Pelvic inflammatory disease refers to a group of infectious diseases of the female upper genital tract, often caused by ascending infection of vaginitis and cervicitis, causing endometritis, salpingitis, tubo-ovarian abscess, pelvic connective tissue inflammation, and/or pelvic peritonitis. PID is the most common and important infectious disease in nonpregnant women of childbearing age, and inflammation in multiple parts often coexists and affects each other. The functional MRI techniques currently used in pelvic floor muscle injury are magnetic resonance diffusion tensor imaging, T2 mapping, and magnetic resonance elastography. Diffusion tensor imaging is a new imaging and postprocessing technology developed on the basis of magnetic resonance diffusion-weighted imaging. Due to the lack of specificity of clinical symptoms, many subclinical patients are often not detected and diagnosed in time, so it is very difficult to accurately estimate the incidence of PID. This article retrospectively analyzed 72 patients with pelvic inflammatory disease confirmed by surgical pathology from February 2020 to 2022, who had undergone pelvic MRI examination before surgery, including 25 patients with chronic pelvic inflammation (hydrosalpinx), 25 patients with acute pelvic inflammation, and 47 cases (including 21 cases of hydrosalpinx, 19 cases of tubo-ovarian abscess, and 7 cases of pelvic abscess). The age range was 13 to 59 years old. The clinical data and MRI findings were analyzed, the ADC value of the cystic part of the lesion was measured, and the differences in age, maximum diameter of the lesion, thickness of the vessel wall/separation, and the ADC value of the cystic part of chronic and acute pelvic inflammation were compared. In this part of the cases, there were 25 cases of chronic pelvic inflammation and 47 cases of acute pelvic inflammation. The average ADC value of the cystic component of chronic inflammation was significantly higher than that of acute inflammation, which were (2.86 ± 0.20) × 10−3 mm2/s and (1.07 ± 0.38) ×10−3 mm2/s, respectively, P value <0.001.

Autophagy and Endoplasmic Reticulum Stress during Onset and Progression of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (AC) is a heritable, potentially lethal disease without a causal therapy. AC is characterized by focal cardiomyocyte death followed by inflammation and progressive formation of connective tissue. The pathomechanisms leading to structural disease onset and progression, however, are not fully elucidated. Recent studies revealed that dysregulation of autophagy and endoplasmic/sarcoplasmic reticulum (ER/SR) stress plays an important role in cardiac pathophysiology. We therefore examined the temporal and spatial expression patterns of autophagy and ER/SR stress indicators in murine AC models by qRT-PCR, immunohistochemistry, in situ hybridization and electron microscopy. Cardiomyocytes overexpressing the autophagy markers LC3 and SQSTM1/p62 and containing prominent autophagic vacuoles were detected next to regions of inflammation and fibrosis during onset and chronic disease progression. mRNAs of the ER stress markers Chop and sXbp1 were elevated in both ventricles at disease onset. During chronic disease progression Chop mRNA was upregulated in right ventricles. In addition, reduced Ryr2 mRNA expression together with often drastically enlarged ER/SR cisternae further indicated SR dysfunction during this disease phase. Our observations support the hypothesis that locally altered autophagy and enhanced ER/SR stress play a role in AC pathogenesis both at the onset and during chronic progression.

Fibromyalgia: transformation of views

Fibromyalgia (FM) is a mystery of modern rheumatology. Despite the high prevalence of FM according to special epidemiological studies, clinicians make this diagnosis rarely. The modern concept of fibromyalgia was created by Smythe and Moldofsky in the mid-70s. They introduced a new term «fibromyalgia», thereby emphasizing that this condition is more due to pain syndrome than inflammation of connective tissue. A disturbance of sensory information processing in the central nervous system (dysfunction of the pain system with the formation of central sensitization, CS) plays a key role in the pathogenesis of FM. Clinical manifestations of FM include chronic widespread pain associated with a wide range of psychosomatic disorders (sleep disorders, cognitive disorders [fibro fog], anxiety, depression, fatigue, morning stiffness, etc.). The diagnostic criteria for fibromyalgia have undergone significant changes. The latest FM diagnostic criteria were developed by the American College of Rheumatology (ACR) in 2016. According to the ACR (2016) FM criteria, a diagnosis of FM does not exclude the presence of other clinically important illnesses. Concomitant FM among patients with rheumatic diseases (RD) occurs 2–3 times more often than in the general population. Diagnostics and treatment of FM are extremely difficult for clinicians, it is especially difficult with comorbidity of FM with RD. Therefore, FM requires a multidisciplinary approach within a biopsychosocial model of pain syndrome: the treatment of a patient with RD and FM should combine anti-inflammatory therapy with a complex of methods (medications and nondrug therapy) used for FM therapy. The diagnostics of comorbid FM in patients with RD will allow for personalized and more effective analgesic therapy.

Comparative evaluation of vegetable matter involved lesions with oral parasitic infections in the oral cavity.

The current research aims to perform a comparative evaluation of vegetable matter involved lesions with oral parasitic infections found in oral mucosa, presenting histochemical methods to differentiate their microscopic similarities. Eight cases were selected out of a sample of 1.975 reports from a single Oral and Maxillofacial Pathology Service of the author's institution from 2012 to 2019. Specimens were examined by hematoxylin and eosin staining (HE), periodic acid-Schiff (PAS) staining, Gomori-Grocott staining, Ziehl-Neelsen staining, Giemsa, and mucicarmine staining. Microscopic analysis included fluorescence, polarized light, and confocal microscopy. Microscopically, in HE coloration, hookworm eggs showed as eosinophilic. Inflammatory multinucleated giant cells and lymphocytes, were usually related to the nematode eggs, forming an intense inflammatory infiltrate. Biofluorescent properties of eggs and larvae revealed to be sensitive in the detection of parasitic structures contrasting with the inflamed connective tissue. Vegetable presence was confirmed by polarized light microscopy and it was found to be associated with microbial biofilms. Confocal microscopy has showed to be an excellent method for morphotype differentiation of parasitic eggs. Parasitic infection and vegetable matter displayed similarities in the inflammatory response, but the latter can rot and agglomerate biofilms. The microscopic diagnosis of such infections requires the interpretation of challenging morphological features since the parasites are usually sectioned and mixed with an inflammatory reaction. These histochemical approaches proved to be excellent to distinguish both lesions.