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The myodural bridge (MDB) is a dense connective tissue bridge connecting the suboccipital muscles to the spinal dura mater, and it has been proven to be a normal common existing structure in humans and mammals. Some scholars believe that the suboccipital muscles can serve as a dynamic cerebrospinal fluid (CSF) pump via the MDB, and they found head rotations promote the CSF flow in human body, which provided evidence for this hypothesis. Head movement is a complex motion, but the effects of other forms of head movement on CSF circulation are less known. The present study explored the effects of head-nodding on CSF circulation. The CSF flow of 60 healthy volunteers was analyzed via cine phase-contrast magnetic resonance imaging at the level of the occipitocervical junction before and after one-minute-head-nodding period. Furthermore, the CSF pressures of 100 volunteers were measured via lumbar puncture before and after 5 times head-nodding during their anesthetizing for surgical preparation. As a result, it was found that the maximum and average CSF flow rates at the level of the upper border of atlas during ventricular diastole were significantly decreased from 1.965 ± 0.531 to 1.839 ± 0.460 ml/s and from 0.702 ± 0.253 to 0.606 ± 0.228 ml/s respectively. In the meantime, the changes in the ratio of cranial and caudal orientation of the net flow volume were found differed significantly after the one-minute-head-nodding period (p = 0.017). And on the other hand, the CSF pressures at the L3–L4 level were markedly increased 116.03 ± 26.13 to 124.64 ± 26.18 mmH2O. In conclusion, the head-nodding has obvious effects on CSF circulation and head movement is one of the important drivers of cerebrospinal fluid circulation. We propose that the suboccipital muscles, participating in various head movements, might pull the dura sac via the myodural bridge, and thus, head movement provides power for the CSF circulation.

A 130-week-old male Royal College of Surgeons rat kept as a non-treated animal in a long-term animal study presented with a mass in the hepatic portal region that adhered to a dilated common bile duct and the duodenum. Histopathologically, the solitary mass showed expansive growth with no apparent compression and continued to dilate the common bile duct, which had a hyperplastic epithelium with intestinal metaplasia. The mass mainly consisted of small to large dilated and/or tortuous ducts with abundant dense connective tissue and many inflammatory cells. The single-layer lining epithelium of the duct changed from cuboidal to columnar. Immunohistochemically, the lining cells were positive for cytokeratin 7, cytokeratin 19, and OV-6, which are bile duct markers. Based on the pathological characteristics, the rat was diagnosed as spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia.

Summary. The aim of the study was to analyze the data of immunohistochemical studies of the lungs after a gunshot wound penetrating at different times. Materials and methods. Lung tissue removed from the wounded with an encapsulated foreign body or without a foreign body of fire origin in the period from 1 day to 10 months after injury was studied. Results and discussion. At 1 day after injury, pathological type IV collagen and transforming growth factor begin to accumulate in the damaged areas. On day 2 of the wound, there is a slight increase in the expression of TGF-β1 and Collagen IV, VEGF is practically not produced, the number of CD68 + macrophages increases. Day 10 was characterized by a progressive increase in the content of transforming growth factor in leukocytes, lymphocytes, fibroblasts, macrophages and collagen type IV in the surrounding wounds. Ten months after injury and surgery, the wound canal was a large area of dense connective tissue with single venous vessels, often without a muscular layer. Transforming growth factor showed pronounced expression in macrophages and vascular endothelium, while VEGF was manifested as a weak positive response in vascular endothelial cells and single macrophages. Type IV collagen remained between the fibers of dense fibrous tissue, which replaced the wound canal, and was also found in the walls of blood vessels, interalveolar membranes, fibroblasts of the adjacent lung parenchyma. Conclusions. 1. Traumatic disorders in the lung parenchyma in FPI in the first hours after injury are accompanied by the accumulation of CD68 + macrophages, which persist for 10 months after FPI and become the main producers of TGF-β1 and VEGF. 2. Transforming growth factor TGF-β1 and vascular-endothelial growth factor VEGF are found in large quantities in macrophages, leukocytes, lymphocytes, fibroblasts and vascular endothelium from the first day of trauma to the lung parenchyma; up to 10 days the expression of TGF-β1 becomes significant, while VEGF weakly marks capillary endotheliocytes, arterioles, single macrophages. This immunohistochemical picture explains the long healing period of FPI. 3. The content of pathological collagen type IV Collagen IV on the first day of gunshot wound is minimal, increases up to 10 days and is detected in the fields of fibrosis and dystelectasis of the lung parenchyma after 10 months. 4. Determination of IHC expression of CD68, TGF-β1, VEGF and Collagen IV in the first 10 days after FPI and in the subsequent stages of treatment of the wounded will help to predict the course of combat trauma and adjust the methods of treatment.

Background: Varanus salvator is one of the reptiles being hunted by human beings for several purposes, including traditional medicine. The studies about reproductive biology aspects were limited. Aim: This study aimed to determine the morphology, histology, and histometry of V. salvator paryphasmata and hemibaculum based on Snout-Vent Length (SVL) as an indicator of sexual maturity. Methods: This study examined 18 pairs of hemipenis of V. salvator with SVL more and less than 40 cm in equal number. Paryphasmata and hemibaculum parts were observed visually and micro-sliced, then stained with Hematoxylin-Eosin (HE). The histological observation was conducted under a 40×, 100×, and 400× magnification of a light microscope. The histometry of the paryphasmata was examined using 13 Megapixels Coolpad and OptiLab Plus for microscopic pictures. The chondrocyte cell area was measured using the Optilab Plus and Image Raster three applications. Results: The sizes of glans of hemipenis, paryphasmata, and hemibaculum increased according to the increasing of SVL. The average paryphasmata row number, epidermis, and loose connective tissue thickness were not significantly different (p > 0.05). However, dense connective tissue was thicker (p < 0.05), which corresponds to SVL. Hemibaculum was composed of fibrous and hyaline cartilage characterized by chondrocyte cells. The SVL also affects (p < 0.05) the ossification of hyaline in hemipenis, while the chondrocyte cell area followed the equation −1.87E7 + 7.09E5* SVL. Conclusion: The SVL size of V. salvator affects the paryphasmata, hemibaculum, thickness of dense connective tissue of paryphasmata, and the area of chondrocyte cells.

Tendons and ligaments are important structures in the musculoskeletal system. Ligaments connect various bones and provide stability in complex movements of joints in the knee. Tendon is made of dense connective tissue and transmits the force of contraction from muscle to bone. They are injured due to direct trauma in sports or roadside accidents. Tendon healing after repair is often poor due to the formation of fibro vascular scar tissues with low mechanical property. Regenerative techniques such as PRP (platelet-rich plasma), stem cells, scaffolds, gene therapy, cell sheets, and scaffolds help augment repair and regenerate tissue in this context. Therefore, it is of interest to document known data (repair process, tissue regeneration, mechanical strength, and clinical outcome) on applied regenerative medicine in tendon healing.

Background The morbidities and complications reported in the reconstruction of large bony defects have inspired progression in the field of bioengineering, with a recent breakthrough for the use of decellularized skeletal muscle grafts (DSMG). Aim To assess the osteogenic potentials of seeded DSMG in vitro and to investigate bone regeneration in critical size defect in vivo. Materials and Methods Assessment of cell viability and characterization was carried out on seeded DSMG for different intervals in vitro. For in vivo experiments, histological analysis was performed for rat cranial defects for the following groups: (A) non-treated DSMG and (B) seeded DSMG after a period of 8 weeks. Results The in vitro experiment demonstrated the lack of cytotoxicity and inert properties of seeded DSMG; these facilitated the osteogenic differentiation and significant gene expressions, particularly of COL1A1, RUNX2, and OPN (1.9174 ± 0.11673, 1.1806 ± 0.02383, and 1.1802 ± 0.00775, respectively). In the in vivo experiment, superior results were detected in the seeded DSMG group which showed highly vascularized and cellular dense connective tissue with deposited bone matrix and multiple scattered islets of newly formed bone. Conclusion Our results demonstrated the promising aspects of DSMG; however, there is a lack of studies to support further implications.

Background High breast density increases breast cancer risk and lowers mammographic sensitivity. Supplemental MRI screening improves cancer detection but increases the number of false-positive screenings. Thus, methods to distinguish true-positive MRI screening results from false-positive ones are needed. Purpose To build prediction models based on clinical characteristics and MRI findings to reduce the rate of false-positive screening MRI findings in women with extremely dense breasts. Materials and Methods Clinical characteristics and MRI findings in Dutch breast cancer screening participants (age range, 50-75 years) with positive first-round MRI screening results (Breast Imaging Reporting and Data System 3, 4, or 5) after a normal screening mammography with extremely dense breasts (Volpara density category 4) were prospectively collected within the randomized controlled Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial from December 2011 through November 2015. In this secondary analysis, prediction models were built using multivariable logistic regression analysis to distinguish true-positive MRI screening findings from false-positive ones. Results Among 454 women (median age, 52 years; interquartile range, 50-57 years) with a positive MRI result in a first supplemental MRI screening round, 79 were diagnosed with breast cancer (true-positive findings), and 375 had false-positive MRI results. The full prediction model (area under the receiver operating characteristics curve [AUC], 0.88; 95% CI: 0.84, 0.92), based on all collected clinical characteristics and MRI findings, could have prevented 45.5% (95% CI: 39.6, 51.5) of false-positive recalls and 21.3% (95% CI: 15.7, 28.3) of benign biopsies without missing any cancers. The model solely based on readily available MRI findings and age had a comparable performance (AUC, 0.84; 95% CI: 0.79, 0.88; P = .15) and could have prevented 35.5% (95% CI: 30.4, 41.1) of false-positive MRI screening results and 13.0% (95% CI: 8.8, 18.6) of benign biopsies. Conclusion Prediction models based on clinical characteristics and MRI findings may be useful to reduce the false-positive first-round screening MRI rate and benign biopsy rate in women with extremely dense breasts. Clinical trial registration no. NCT01315015 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Imbriaco in this issue.

The problem of anterior cruciate ligament (ACL) reconstruction of the knee joint remains relevant, despite of significant number of designed surgical techniques for its reconstruction. Repeated ruptures of the restored ACL are recorded in 3–15 % of cases. Objective: to determine the morphological features of the knee joint tissues rearrangement in rabbits after implantation of a polypropylene mesh (PM) into the capsule defect. Methods: the study was performed on 50 rabbits weighing (694 ± 27) g. A capsule defect was formed on the right knee joint between the patellar ligament and the medial collateral ligament. In the experimental group (25 rabbits), the defect was repaired using PM, in the control group (25) — the edges of the defect were tightened and sutured with vicryl. A modified Vanderbilt University scale was used to assess the scarring process. Morphological analysis was performed. Results: no significant clinical differences in the state of the operated knee joint in the postoperative period were found between the groups. In the control group, from the 7th day after the surgery, the formation of dense connective tissue (scar) was observed. In animals of the experimental group, against the background of the formation of connective tissue around the PM, a significant thickening of the capsule and ligaments was observed at the points of contact with it. In 21 days after PM implantation, 51–75 % of its area showed ingrowth of connective tissue, after 45 — 75–100 %. After 2 months after the surgery, the relative area of dense connective tissue in the experiment was (68.12 ± 2.74) % versus (51.68 ± 4.22) % in the control.Conclusions: implantation of PM into the area of the knee joint capsule defect of rabbits between the patellar ligament and the medial collateral led to the formation of a larger volume of dense connective tissue at the final follow-up period (2 months). Ingrowth of connective tissue between cells and fibers of PM promotes the formation of a tight connection with the surrounding tissues, thereby strengthening area of traumatic injury.

Background A major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium). Results In two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies. Conclusions The novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.

Purpose The palatopharyngeus is one of the longitudinal pharyngeal muscles which contributes to swallowing. It is reported that the palatopharyngeus has muscle bundles in various directions and with attachment sites, and each muscle bundle has a specific function. Although previous reports suggest that the palatopharyngeus is partly interlaced with some parts of the inferior constrictor, the precise relationship remains unclear. The purpose of this study was to examine the precise manner of the connection between the palatopharyngeus and inferior constrictor, and to examine the histological characteristics of this connection. Methods We examined 15 halves of nine heads from Japanese cadavers (average age: 76.1 years); 12 halves, macroscopically, and three halves, histologically. Results Our observation suggests that the palatopharyngeus spreads radially on the inner aspect of the pharyngeal wall. The most inferior portion of the palatopharyngeus extended to the inner surface of the cricopharyngeal part of the inferior constrictor. Histological analysis showed that the inferior end of the palatopharyngeus continued into the dense connective tissue located at the level of the cricoid cartilage. The dense connective tissue not only covered the inner surface of the inferior constrictor but also entered its muscle bundles and enveloped them. Conclusion Therefore, the palatopharyngeus interlaced the cricopharyngeal part of the inferior constrictor through the dense connective tissues. The findings of this study show that the palatopharyngeus may act on the upper esophageal sphincter directly and help in its opening with the aid of the pulling forces in the superolateral direction.

One of the urgent problems of modern surgery continues to be the increasing number of patients with purulent-inflammatory and purulentnecrotic processes of soft tissues – about 60.0 % of patients in the structure of specialized hospitals of a surgical profile. This is due to the adaptation of microorganisms – pathogens of wound infection to existing means for treating wounds. In addition, the number of patients with diabetes mellitus increases annually, and as a result, the number of people suffering from diabetic foot syndrome. Thus, the relevance of developing new modern tools for the local treatment of purulent-necrotic processes of the skin and soft tissues is not reduced.Materials and methods.The material for the study was a highly porous biodegradable sponge (chitosan-collagen) in the ratio of chitosan: collagen 2: 1 with the inclusion of colloidal particles of metallic silver and chymotrypsin. The experiment was performed on 50 Wistar rats that simulated a purulent necrotic wound. During the treatment, the state of the wounds was visually evaluated, the morphological features of the course of the wound process were evaluated after animals were withdrawn from the experiment and the wound material was taken on days 1, 5, 10, 15 and 21, the sections were stained with hematoxylin-eosin and/or according to Van Gieson.Results.By visual assessment, by the 10th day it was noted that necrotic tissues underwent lysis, the wound defect was covered with a scab, swelling of the surrounding tissues was not noted, and on the 21st day of treatment the wound defect was covered with epithelium and had an area of about 3 mm2 with the initial - in 250 mm2. When describing micropreparations, it was noted that on the 10th day the exudation phase passed its peak and the activity of proliferation processes increased from the center of the wound to its periphery and from the granulation surface in depth. On the 15th day, the proliferative phase of inflammation was at its height, and on the 21st day, the proliferation phase was completed and the processes of remodeling of dense fibrous connective tissue began.Conclusion.Based on a visual assessment of the state of wounds and a morphological study, the effectiveness of a chitosan-collagen complex with silver nanoparticles and chymotrypsin was shown to be applied locally to a purulent necrotic wound in an experiment.

Objective: The aim of this case report is to describe the surgical removal of a mucocele and its histological analysis, in a child. Case Report: An 11-year-old female patient attended the Pediatric Dentistry clinic complaining of a lower lip lesion. During the anamnesis, the mother reported that the child had a habit of biting and sucking the spot frequently. Clinical examination showed the lesion was compatible with a mucocele. The proposed treatment was a complete enucleation of the lesion under local anesthesia. The incision and tissue divulsion were performed for maximum preservation of the mucosa, avoiding a possible recurrence. Total adjacent glands removal was also performed. The lesion was placed in 10% formaldehyde for histopathological analysis (H&E Staining), which showed dense connective tissue presenting chronic inflammatory infiltrate and extravasated mucin, presence of granulation tissue delimiting the area of extravasated mucin and presence of minor salivary glands. The patient was advised to quit the habit, and after seven days the sutures were removed. At the one-year follow-up there was no recurrence of the lesion. Conclusion: The proposed treatment proved to be effective without recurrence of the lesion.

Lipodermoids are abnormal epibulbar growths of the adipose tissue. A conjunctival lesion, the lipodermoid (dermolipoma) is usually located near the temporal fornix and is composed of adipose tissue and dense connective tissue. The overlying conjunctival epithelium is normal, and hair follicles are absent. Lipodermoids may be extensive, sometimes involving orbital tissue, lacrimal gland, and extraocular muscle. Surgical treatment is only indicated when the existing lipodermoid disturbs the patient either functionally or aesthetically. Purpose The main purpose of this study is to present our experience on the surgical treatment of lipodermoids in those cases when lipodermoids cause functional and aesthetic problem to the patient. Materials and Methods In our study we have included two cases of male gender, one with bilateral lipodermoid (in both eyes) while the other with a mono lateral lipodermoid (only in one eye). The treatment was surgical, where we carefully removed the lipodermoid lesion inside palpebral fissures, to fully preserve the bulbar conjunctiva and Tenon’s membrane during the removal of the conjunctival lipodermoid.Surgery was performed under local anesthesia (lidocaine 2% and adrenaline). The surgical area was set ready by using betadine 5%. Results In both cases there were neither intra-operative nor extra-operative complications and the results were positive.Also the functional and aesthetic problems were corrected. There was no recurrence encountered.Conclusions In conclusion, based on the results of this study, in the rare cases of lipodermoids where surgical treatment is necessary, it is very important to perform a careful surgical intervention, in order to prevent any intra-operative injuries of the lacrimal gland and the lateral and superior rectus muscles. In general the surgical treatment is a successful method on treating lipodermoids, in cases when they concern the patient both functionally and aesthetically.

Summary Loss of nuclear integrity correlates with increased DNA damage in different tissues. In a recent issue of Cell, Nader et al. reveal that nuclear envelope ruptures in dense tissue microenvironments cause TREX1-dependent DNA damage and promote the transition from in situ to invasive carcinomas.

Mouse and human teeth represent challenging organs for quick and efficient cell isolation for single-cell transcriptomic or other applications. The dental pulp tissue, rich in the extracellular matrix, requires a long and tedious dissociation process that is typically beyond the reasonable time for single-cell transcriptomics. For avoiding artificial changes in gene expression, the time elapsed from euthanizing an animal until the analysis of single cells needs to be minimized. This work presents a fast protocol enabling to obtain single-cell suspension from mouse and human teeth in an excellent quality suitable for scRNA-seq (single-cell RNA-sequencing). This protocol is based on accelerated tissue isolation steps, enzymatic digestion, and subsequent preparation of final single-cell suspension. This enables fast and gentle processing of tissues and allows using more animal or human samples for obtaining cell suspensions with high viability and minimal transcriptional changes. It is anticipated that this protocol might guide researchers interested in performing the scRNA-seq not only on the mouse or human teeth but also on other extracellular matrix-rich tissues, including cartilage, dense connective tissue, and dermis.

Tissue specimens taken from primary tumors or metastases contain important information for diagnosis and treatment of cancer patients. Multispectral imaging allows in situ visualization of heterogeneous cell subsets, such as lymphocytes, in tissue samples. Many image processing pipelines first segment cell boundaries and then measure marker expression to assign cell phenotypes. In dense tissue environments such as solid tumors, segmentation-based phenotyping can be inaccurate due to segmentation errors or overlapping cell boundaries. Here we introduce a machine learning pipeline design called ImmuNet that directly identifies the positions and phenotypes of immune cells without determining their exact boundaries. ImmuNet is easy to train: human annotators only need to click on immune cells and rank their expression of each marker; full annotation of tissue regions is not necessary. We demonstrate that ImmuNet is a suitable approach for immune cell detection and phenotyping in multiplex im-munohistochemistry: it compares favourably to segmentation-based methods, especially in dense tissues, and we externally validate ImmuNet results by comparing them to flow cytometric measurements from the same tissue. In summary, ImmuNet performs well on diverse tissue specimens, takes relatively little effort to train and implement, and is a simpler alternative to segmentation-based approaches when only cell positions and phenotypes, but not their shapes are required for downstream analyses. We hope that ImmuNet will help cancer researchers to analyze multichannel tissue images more easily and accurately.

A 65-year-old man with a chief complaint of rhinorrhea was referred to our hospital. A dental implant was placed 11 years prior to his referral, and prosthetic treatment was performed at the same dental clinic. X-ray imaging showed a migrated dental implant surrounded by dense tissue containing small radiopaque particles in the left maxillary sinus. The migrated dental implant and surrounding amorphous mass were removed under general anesthesia. Histopathological examination of the extracted object showed hyphae of Aspergillus and a thickened sinus membrane with infiltration of inflammatory cells. Therefore, we diagnosed the patient with maxillary sinus aspergillosis. Chemotherapeutic treatment with clarithromycin was performed after surgery; however, the symptoms persisted for a year. We consulted the department of otolaryngology, and endoscopic sinus surgery was performed. After surgery, the symptoms gradually subsided.

Anterior cruciate ligament is one of the most common ligaments to get injured especially in athletic population. It is a band of dense connective tissue which arises from the antero-medial aspect of the inter condylar area on the tibial plateau and passes upwards and backwards to attach to the posteromedial aspect of the lateral femoral condyle. There is increasing rate of its reported injuries among athletes in Nepal and surgeons report increased consultations among athletes regarding adequate intervention strategies. Factors like over use, inadequate recovery time, playing surface, fitness incompatibility are involved in the increase of anterior cruciate ligament injury among athletes in Nepal. Treatment approach for anterior cruciate ligament injury is ever evolving with regular studies and innovation, but constant guidance and rehabilitation in an institution-based setting have shown positive feedback in recovery and return to play.

A 34-year-old female patient attended a referral center for oral diagnosis presenting hardened increased volume in the posterior mandible. Panoramic radiography revealed a mixed unilocular lesion with clear and well-defined limits. The incisional biopsy showed proliferation of mesenchymal cells amid dense fibrous connective tissue. Mineralized material in different degrees of maturation was also observed. Regarding the histopathological aspects associated with the clinical, radiographic, and intraoperative data, the diagnosis of central ossifying fibroma (COF) was performed. COF has similar characteristics to other fibro-osseous lesions, and its diagnosis is a challenge for dental surgeons.

Background. Regeneration of bone defects remains a challenge for maxillofacial surgeons. The present study aimed to compare the effects of octacalcium phosphate (OCP) and the combination of octacalcium phosphate/gelatin (OCP/Gel) on mandibular bone regeneration in rats Methods. In the present study, 36 male Sprague-Dawley rats were used. The animals were randomly assigned to the following experimental groups: OCP (n=12), OCP/Gel (n=12), and the control group (n=12). Defects were created in the rat mandibles and filled with 10 mg of OCP and OCP/Gel disks in the experimental groups. In the control group, however, no substance was administered. Samples were taken on days 7, 14, 21 and 56, respectively, after the implantation. Sections (5 µ) were prepared and stained by H&E. The sections were studied, and the volume fraction of newly formed bone was measured by Dunnett's T3 test based on the significance level (P=0.05). Results. In the experimental groups, the new bone formation began from the margin of defects 7‒14 days after the implantation. During the healing process, the newly formed bone healed a larger area of the defects and grew structurally. In the control group, the defects were primarily filled with dense connective tissue, and only a small amount of new bone was formed. The present study showed a statistically significant difference in the volume of newly formed bone between the experimental groups and the control group (PConclusion. OCP/Gel composite can be beneficial in the healing process of mandibular bone defects.

Background. The scientific literature contents clearly not enough data at interaction of collagen materials with a living organism and about influence of multipotent stromal cells (MSC) on this process. There are controversies about the collagen degradation and the development of foreign body reactions. However, without account these results, it is impossible to estimate the timeframes for complete lysis of such materials, to progress effective methods for the prevention and treatment of developing complications. Objective. To study the features of the collagen-based material degradation after implantation with adsorbed autologous mesenchymal MSC of bone marrow origin (AMMSCBMO) in the experiment. Design and methods. In different times the condition of tissues around the implanted collagen membrane with adsorbed AMMSCBMO was studied by method of light microscopy. Results. The number of vessels and cellular elements in the collagen material implanted without AMMSCBMO increases to 3 weeks and remains at this level until the end of the observation. A distinctive features of the use of collagen membrane with adsorbed AMMSCBMO are increased vascularization and cellular infiltration of the material in the first 2 weeks after surgery. This effect further leads to a more rapid degradation of all implanted collagen, including its more dense parts, but does not prevent the formation of multinuclear macrophages with fused cytoplasm. Conclusion. As a result of more significant vascularization and cellular infiltration caused by AMMSCBMO adsorbed on the surface of the collagen material, to the 4th week the entire implant is full destroyed and absorbed, and dense fibrous connective tissue is formed in its place. For the implantation into the body, one should choose the most homogeneous collagen materials, without areas of different density, as slowly degrading fragments can cause the development of granulomatous inflammation and the failure of the implantation procedure.

Arachnoid granulations are outpouchings of arachnoid membrane which extend into the dural sinuses or calvarium, surrounded by a capsule of dense connective tissue. Within dural sinuses, these appear as well-defined, nodular, rounded, or ovoid structures of focal localization. However, it is important to be aware of their variability in presentation in order to correctly identify them and distinguish them from other dural sinus pathology, especially a misdiagnosis of venous sinus thrombosis with risks of unnecessary anticoagulation, intravascular thrombolysis/thrombectomy, or invasive intracranial pressure monitoring. Here we demonstrate a case of a previously unreported giant intrasinus arachnoid granulation of an unusual vermiform morphology, unduly elongated up to 6 cm in length, involving a significant segment of the superior sagittal sinus. The proof of this diagnosis was the radiologic appearance on multiple modalities and an unchanged appearance over the long-term. Keywords: Arachnoid granulation, Giant, Vermiform, Morphology

Purpose This study aimed to morphologically and histologically investigate the relationship between deep subregions of the rotator cuff muscle and shoulder joint capsule as well as the relationship between the rotator cuff tendon or capsule and bony insertion. Methods We examined 13 shoulders of embalmed cadavers and measured the capsular attachments and footprints macroscopically. We also histologically examined the fibres in three shoulders. Results Loose attachment, which was less tight with spaced connective tissue, and firm attachment, which was tight with dense connective tissue, were found under the surface of the supraspinatus and infraspinatus. The anterior-deep and posterior-deep subregions of the supraspinatus and the middle partition and inferior partition of the infraspinatus formed firm attachments to the capsule. The mean areas of firm attachment for the anterior-deep subregion, posterior-deep subregion and middle partition were 118.8 mm2, 267.8 mm2 and 399.3 mm2, respectively, while the area of the inferior partition was small. The transverse fibres were located just lateral to the medial edge of the firm attachment area. The thick capsule had a substantial footprint. Both tendon fibres and the capsule inserted into the superior and middle facets through the attachment fibrocartilage. Conclusions The posterior-deep subregion of the supraspinatus and middle partition of the infraspinatus evenly occupied the capsular attachment area. The transverse fibres were located just lateral to the medial edge of the firm attachment area, and the thick capsule had a substantial footprint. Both tendon fibres and the capsule inserted into the superior and middle facets through the attachment fibrocartilage.

Background/objective Stem cell–based therapy has been applied to accelerate the revitalization of allograft tendon into a viable and functional tendon. Although many authors have proposed different methods to help the seeded stem cell distribution in the decellularized allograft, limited success has been achieved as tendon is a high dense connective tissue. We hypothesized that bone marrow stromal cells (BMSCs), seeded through the lateral slit, can regenerate the decellularized tendon (DCT) graft. The cell proliferation, cell viability, and tendon-specific gene expression are increased with the seeded cell density. Methods Eighty-seven flexor digitorum profundus tendons were equally and randomly divided into 6 treatment groups that were seeded with low-density (2 × 107 cells/mL) and high-density (5 × 107 cells/mL) BMSCs through lateral slits cultured for 2 and 4 weeks, DCT without cells, and fresh live tendons. Tendons were evaluated for cell distribution, cell proliferation, cell viability, gene expression of Collagen I and Collagen III, tenogenic markers, and MMPs. Results Histologic evaluation revealed BMSCs distributed from the lateral slit to the whole DCT. BMSCs were proliferated and kept viable in lateral slit decellularized tendon (LSDCT) in both seeded cell density groups after 2 and 4 weeks of culture. However, no significant differences in the cell proliferation between both cell density groups at 2 and 4 weeks of culture were observed. The lowest cell viability was found in the high-density group after 4 weeks of culture. BMSCs in LSDCT showed a significant tendency of higher gene expression of Collagen I, Collagen III, tenascin C, MMP2, MMP9, and MMP13 compared to normal tendons in both cell density groups at 2 and 4 weeks of culture. Conclusion BMSCs proliferated and remained viable after 2 and 4 weeks of culture with distribution throughout the lateral slits. Lateral slit preparation allows for the effective delivery and maintenance of mesenchymal cells with proliferation and generating a tenogenic behaviour of DCT in both the low and high cell densities in an in vitro model. The translation potential of this article Revitalizing the implanted decellularized allograft is important for clinical application. In this study, we demonstrated that the DCT, with lateral slits, could harbour the seeded stem cell and stimulate proliferation with collagen synthesis. This evidence was presented for clinical application of the lateral slit technique, in DCT grafts, which would repopulate the seeded BMSCs during tendon and ligament reconstruction.

This work focuses on the automatic quantification of the breast density from digital mammography imaging. Using only categorical image-wise labels we train a model capable of predicting continuous density percentage as well as providing a pixel wise support frit for the dense region. In particular we propose a weakly supervised loss linking the density percentage to the mask size.

Rationale and Objectives High mammographic density reduces the diagnostic accuracy of screening mammography due to masking of tumors, resulting in possible delayed diagnosis and missed cancers. Women with high masking risk could be preselected for alternative screening regimens less susceptible to masking. In this study, various models to predict masking status are presented based on biometric and image-based parameters. Materials and Methods For a cohort of 67 nonscreen-detected (cancers detected via other means after a negative mammogram) and 147 screen-detected invasive cancers, quantitative volumetric breast density, BI-RADS density, and the distribution and appearance of dense tissue through statistical and texture metrics were measured. Age and Body Mass Index were recorded. Stepwise multivariate logistic regressions were computed to select those parameters that predicted nonscreen-detected cancers. Accuracy of the models was evaluated using the area under receiver operator characteristic curve (AUC). Results Using BI-RADS density alone to predict masking risk yielded an AUC of 0.64 (95% confidence interval [0.57–0.70]). Age-adjusted BI-RADS density or volumetric breast density had AUCs of 0.72 [0.64–0.79] and 0.71 [0.62–0.78], respectively. A model extracted from the full pool of variables had an AUC of 0.75 [0.67–0.82]. Conclusion The optimal model predicts masking more accurately than density alone, suggesting that texture metrics may be useful in models to guide a stratified screening strategy.

We evaluated the association between short-term change in body mass index (BMI) and breast density during a 1 year weight-loss intervention (Manchester, UK). We included 65 premenopausal women (35–45 years, ≥7 kg adult weight gain, family history of breast cancer). BMI and breast density (semi-automated area-based, automated volume-based) were measured at baseline, 1 year, and 2 years after study entry (1 year post intervention). Cross-sectional (between-women) and short-term change (within-women) associations between BMI and breast density were measured using repeated-measures correlation coefficients and multivariable linear mixed models. BMI was positively correlated with dense volume between-women (r = 0.41, 95%CI: 0.17, 0.61), but less so within-women (r = 0.08, 95%CI: −0.16, 0.28). There was little association with dense area (between-women r = −0.12, 95%CI: −0.38, 0.16, within-women r = 0.01, 95%CI: −0.24, 0.25). BMI and breast fat were positively correlated (volume: between r = 0.77, 95%CI: 0.69, 0.84, within r = 0.58, 95%CI: 0.36, 0.75, area: between r = 0.74, 95%CI: 0.63, 0.82, within r = 0.45, 95%CI: 0.23, 0.63). Multivariable models reported similar associations. Exploratory analysis suggested associations between BMI gain from 20 years and density measures (standard deviation change per +5 kg/m2 BMI: dense area: +0.61 (95%CI: 0.12, 1.09), fat volume: −0.31 (95%CI: −0.62, 0.00)). Short-term BMI change is likely to be positively associated with breast fat, but we found little association with dense tissue, although power was limited by small sample size.

The 2D wavelet transform modulus maxima (WTMM) method is used to perform a comparison of the spatial fluctuations of mammographic breast tissue from patients with invasive lobular carcinoma, those with invasive ductal carcinoma, and those with benign lesions. We follow a procedure developed and validated in a previous study, in which a sliding window protocol is used to analyze thousands of small subregions in a given mammogram. These subregions are categorized according to their Hurst exponent values (H): fatty tissue (H ≤ 0.45), dense tissue (H ≥ 0.55), and disrupted tissue potentially linked with tumor-associated loss of homeostasis (0.45 < H < 0.55). Following this categorization scheme, we compare the mammographic tissue composition of the breasts. First, we show that cancerous breasts are significantly different than breasts with a benign lesion (p-value ∼ 0.002). Second, the asymmetry between a patient’s cancerous breast and its contralateral counterpart, when compared to the asymmetry from patients with benign lesions, is also statistically significant (p-value ∼ 0.006). And finally, we show that lobular and ductal cancerous breasts show similar levels of disruption and similar levels of asymmetry. This study demonstrates reproducibility of the WTMM sliding-window approach to help detect and characterize tumor-associated breast tissue disruption from standard mammography. It also shows promise to help with the detection lobular lesions that typically go undetected via standard screening mammography at a much higher rate than ductal lesions. Here both types are assessed similarly.

The Peripheral Ossifying Fibroma is a benign tumor that develops from a hyperplastic tissue reaction, usually related to traumatic stimulus that are responsible for triggering inflammatory reactions of the connective tissue. Histologically, it is a nodular mass characterized by a dense connective tissue, surrounded by stratified squamous epithelium. Surgical removal in these cases is indicated, and for reconstruction of soft tissue in the region, some periodontal surgical techniques are recommended, such as free gingival grafting. Thus, the present study aims to report a clinical case submitted to the free gingival graft technique for tissue reconstruction after the surgical removal of a fibroma. A total excision of the lesion was performed, later sent to a histopathological report where it was diagnosed as Peripheral Ossifying Fibroma, after the removal of the lesion the region was left with the periosteum exposed and then the free gingival graft was performed to cover the region and promote keratinized gum augmentation. This technique proved to be efficient for reconstruction of soft tissue in the region after surgical removal of the Peripheral Ossifying Fibroma, returning aesthetics, function and periodontal health. El fibroma osificante periférico es un tumor benigno que se desarrolla a partir de una reacción tisular hiperplásica, generalmente relacionada con estímulos traumáticos que son responsables de desencadenar reacciones inflamatorias del tejido conectivo. Histológicamente, es una masa nodular caracterizada por un tejido conectivo denso, rodeado de epitelio escamoso estratificado. La extirpación quirúrgica en estos casos está indicada, y para la reconstrucción de los tejidos blandos de la región, están indicadas algunas técnicas quirúrgicas periodontales, como el injerto gingival libre. Así, el presente estudio tiene como objetivo informar de un caso clínico sometido a la técnica del injerto gingival libre para la reconstrucción de tejidos tras la extirpación quirúrgica de un fibroma osificante periférico. Se realizó una escisión total de la lesión, posteriormente se envió a informe histopatológico donde se diagnosticó como fibroma, tras la extirpación de la lesión se dejó la región con el periostio expuesto y posteriormente se realizó el injerto gingival libre para cubrir la región y promover el agrandamiento gingival queratinizado. Esta técnica demostró ser eficaz para la reconstrucción de los tejidos blandos de la región tras la extirpación quirúrgica del fibroma, com la devolución de la estética, la función y la salud periodontal. O Fibroma Ossificante Periférico é tumor benigno que se desenvolve a partir de uma reação hiperplásica tecidual, habitualmente relacionada a estímulos traumáticos que são responsáveis por desencadear reações inflamatórias do tecido conjuntivo. Histologicamente, é uma massa nodular caracterizada por um tecido conjuntivo denso, circundado por epitélio escamoso estratificado. A remoção cirúrgica nestes casos é indicada, e para reconstrução de tecido mole na região, algumas técnicas cirúrgicas periodontais são indicadas, como o enxerto gengival livre. Assim, o presente estudo tem como objetivo relatar um caso clínico submetido à técnica de enxerto gengival livre para reconstrução tecidual após a remoção cirúrgica de um fibroma. Foi realizada a excisão total da lesão, posteriormente enviado para laudo histopatológico onde foi diagnosticada como fibroma, após a remoção da lesão a região ficou com o periósteo exposto e então foi realizado o enxerto gengival livre para recobrir a região e promover aumento de gengiva queratinizada. Esta técnica se mostrou eficiente para reconstrução do tecido mole na região após a remoção cirúrgica do fibroma. Devolvendo estética, função e saúde periodontal.

Background : Lipomas are adipocytic tumors of slow and expansive growth. They can be classified into several subtypes depending on the tissue present next to the neoplastic adipocytes. One of such subtypes is the fibrolipoma, which is formed by well-differentiated adipocytes and fibrous connective tissue. This neoplasm has been little described in cattle, and rare reports present the treatment and resolution of the case. Thus, the dissemination of cases of fibrolipomas in cattle is essential to help veterinarians diagnose this neoplasm. The present report describes a case of fibrolipoma in the distal pelvic limb of a cow successfully treated by surgical excision. Case : A 4-year-old 3/4 Girolando cow from the municipality of Vazante-MG, Brazil, was treated on the farm. According to the owner, the animal had been showing tumoral growth in the left pelvic limb over the period of 1 year and 3 months. The tumor involved the entire left metatarsus and was 40 x 37 cm, without ulcerations and painless on palpation. A neoplasm was suspected and surgical excision was the chosen approach. The cow was sedated, positioned and restrained in right lateral recumbency for surgery. The operative field was prepared and a subcutaneous locoregional ring block was performed dorsally to the tumor. The tumor mass was excised with a safety margin of 1 cm. After removal, the mass was found to weigh 10.4 kg and to be yellowish-white upon sectioning. Due to the distance between the edges of the surgical wound, skin suture could not be performed. Thus, second-intention healing and wound protection with bandages were the choice of management. In the postoperative period, the adopted treatment consisted of antibiotic therapy with benzathine penicillin, analgesia with non-steroidal anti-inflammatory drugs, daily dressings and wound protection with bandages. The animal did not show postoperative complications and, over 8 months of monitoring after surgery, there was no recurrence of the neoplasm and the cow was in productive activity. Tumor fragments were fixed in 10 % buffered formalin and sent for histopathological examination, which revealed a neoplasm of mesenchymal cells in the subcutaneous adipose tissue supported by dense fibrovascular stroma with solid arrangement. A large amount of dense connective tissue was found among the neoplastic cells. In view of these findings, the diagnosis of fibrolipoma was established. Discussion : Fibrolipoma is a benign neoplasm little described in the veterinary literature, especially in cattle, with only 3 cases reported. To the knowledge of the authors, this is the first report of this neoplasm in the distal limb of cattle. Fibrolipomas are a rare type of lipoma formed by well-differentiated lipocytes and fibrous tissue. The fibrolipoma described in this report was 40 cm in diameter and weighed 10.4 kg, so it can be classified as a type of giant lipoma, as it was more than 10 cm in diameter and more than 1 kg in weight. In the present report and in others in the medical literature, surgical removal of the fibrolipoma resulted in complete recovery of the patient without postoperative complications. Surgical excision is the treatment of choice in these cases and usually promotes healing. However, surgery must be performed early and the neoplasm must be completely removed. The histological characteristics of the fibrolipoma in this case are similar to those found in other cases in cattle and corroborate the choice for surgical treatment and maintenance of the animal in the herd. Although rare, fibrolipomas should be included in the differential diagnosis of tumors of slow and expansive growth in cattle. Keywords: bovine, adipose tissue, lipoma, neoplasia, surgery. Descritores: bovino, cirurgia, tecido adiposo, lipoma, neoplasia. Titulo: Fibrolipoma gigante no membro distal de uma vaca

Recent studies have evidenced that the anatomical structure now known as the myodural bridge (MDB) connects the suboccipital musculature to the cervical spinal dura mater (SDM). In humans, the MDB passes through both the posterior atlanto-occipital and the posterior atlanto-axial interspaces. The present authors suggest that the MDB has important physiological functions in humans. The existence of the MDB in various mammals, including flying birds (Rock pigeons and Gallus domesticus) has been previously validated. Gentoo penguins are marine birds, able to make 450 dives per day, reaching depths of up to 660 feet. Gentoo penguins are also the world’s fastest diving birds. The present study was therefore carried out to investigate the existence and characteristics of the MDB in Gentoo penguin (Pygoscelis papua), a non-flying, marine bird that can dive. While foraging, this penguin is able to reach speeds of up to 22 miles per hour. For this study, six Gentoo penguin specimens were dissected to observe the existence and composition of their MDB. Histological staining was also performed to analyze the anatomic relationships and characteristic of the MDB in the Gentoo penguin. In this study, it was found that the suboccipital musculature in the Gentoo penguin consists of the rectus capitis dorsalis minor (RCDmi) muscle and rectus capitis dorsalis major (RCDma) muscle. Dense connective tissue fibers were observed connecting these two suboccipital muscles to the spinal dura mater (SDM). This dense connective tissue bridge consists of primarily type I collagen fibers. Thus, this penguin’s MDB appears to be analogous to the MDB previously observed in humans. The present study evidences that the MDB not only exists in penguins but it also has unique features that distinguishes it from that of flying birds. Thus, this study advances the understanding of the morphological characteristics of the MDB in flightless, marine birds.

Introduction: Dense fibrous connective tissue is inherently found in the human sinoatrial node (hSAN), which further increases in heart failure (HF) leading to sinoatrial node dysfunction (SND). While several factors contribute to cardiac fibrosis, it is unknown if long non-coding RNAs (lncRNA), a novel class of RNA known to affect cardiac fibrosis, are involved in increasing fibrotic content in hSAN in non-failing (nHF) vs HF hearts. Objective: To identify unique lncRNA profiles and pro-fibrotic lncRNAs in isolated SAN and right atrial (RA) fibroblasts (FBs), in HF vs nHF human hearts. Methods: FBs isolated from pure SAN and RA tissues, from HF (n=6; 35-68yo) and nHF (n=4; 26-64yo) cardioplegically arrested human hearts, were cultured with/without transforming growth factor β1 (TGFβ1; 5ng; 48hrs) to activate myofibroblast (myoFB) transition. Frozen FBs and myoFBs were subjected to high throughput Next Generation RNA Sequencing analyses of the whole transcriptome. Results: Averages of total counts across all samples revealed that majority of the genes detected were protein coding 14415(63%), 5876 (26%) lncRNA, 1254 (5%) miscellaneous RNA, 677(3%) miRNA and 577 (3%) other types of RNA (Figure A). Preliminary analyses show that coding mRNA and non-coding lncRNA are differentially expressed in nHF hSAN and RA fibroblasts and TGFβ1 treated myoFBs. Furthermore, these expression patterns were also different in FBs and myoFBs isolated from failing hearts. Conclusions: Our findings show for the first time that lncRNA expression in cultured hSAN Fbs and myoFBs are unique and differentially altered in HF. Ongoing analyses of sequenced transcriptome will identify FB and myoFB lncRNAs associated with intrinsic higher levels of hSAN fibrotic content as well as in HF. We will also determine if they can modify pro-fibrotic activity in HF SAN FBs and myoFBs, which may be beneficial to develop novel molecular approaches to decrease HF-associated SAN fibrosis and associated SND.

Digital breast tomosynthesis (DBT) is an emerging breast cancer screening and diagnostic modality that uses quasi-three-dimensional breast images to provide detailed assessments of the dense tissue within the breast. In this study, a framework of a 3D-Mask region-based convolutional neural network (3D-Mask RCNN) computer-aided diagnosis (CAD) system was developed for mass detection and segmentation with a comparative analysis of performance on patient subgroups with different clinicopathological characteristics. To this end, 364 samples of DBT data were used and separated into a training dataset (n = 201) and a testing dataset (n = 163). The detection and segmentation results were evaluated on the testing set and on subgroups of patients with different characteristics, including different age ranges, lesion sizes, histological types, lesion shapes and breast densities. The results of our 3D-Mask RCNN framework were compared with those of the 2D-Mask RCNN and Faster RCNN methods. For lesion-based mass detection, the sensitivity of 3D-Mask RCNN-based CAD was 90% with 0.8 false positives (FPs) per lesion, whereas the sensitivity of the 2D-Mask RCNN- and Faster RCNN-based CAD was 90% at 1.3 and 2.37 FPs/lesion, respectively. For breast-based mass detection, the 3D-Mask RCNN generated a sensitivity of 90% at 0.83 FPs/breast, and this framework is better than the 2D-Mask RCNN and Faster RCNN, which generated a sensitivity of 90% with 1.24 and 2.38 FPs/breast, respectively. Additionally, the 3D-Mask RCNN achieved significantly (p < 0.05) better performance than the 2D methods on subgroups of samples with characteristics of ages ranged from 40 to 49 years, malignant tumors, spiculate and irregular masses and dense breast, respectively. Lesion segmentation using the 3D-Mask RCNN achieved an average precision (AP) of 0.934 and a false negative rate (FNR) of 0.053, which are better than those achieved by the 2D methods. The results suggest that the 3D-Mask RCNN CAD framework has advantages over 2D-based mass detection on both the whole data and subgroups with different characteristics.

Desmoplastic fibroblastoma (also known as collagenous fibroma) is an uncommon benign fibroblastic/ myofibroblastic neoplasm that primarily arises in the subcutaneous tissue of upper extremity. Magnetic resonance imaging reveals a well-defined mass in intimate association with dense connective tissue and prominent low signal intensity on all pulse sequences. Peripheral and septal enhancement is usually seen after intravenous contrast. Histologically, the lesion is paucicellular and consists of spindle to stellate-shaped cells embedded in a collagenous or myxocollagenous stroma with low vascularity. Diffuse and strong nuclear immunoreactivity for FOS-like antigen 1 seems to be characteristic of desmoplastic fibroblastoma. Cytogenetic studies have demonstrated the presence of 11q12 rearrangements and an identical t(2;11)(q31;q12) translocation. This review provides an updated overview of the clinical, radiological, histological, cytogenetic and molecular genetic features of desmoplastic fibroblastoma and discusses the relationship to fibroma of tendon sheath.

Tendon is a dense connective tissue that stores and transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, yet little is known about the diversity of cell types that populate tendon. To address this, we determined the heterogeneity of cell populations within mouse Achilles tendons using single-cell RNA sequencing. In assembling a transcriptomic atlas of Achilles tendons, we identified 11 distinct types of cells, including three previously undescribed populations of tendon fibroblasts. Prior studies have indicated that pericytes, which are found in the vasculature of tendons, could serve as a potential source of progenitor cells for adult tendon fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are likely to be at least one of the progenitor cell populations for the fibroblasts that compose adult tendons. We also modeled cell-cell interactions and identified previously undescribed ligand-receptor signaling interactions involved in tendon homeostasis. Our novel and interactive tendon atlas highlights previously underappreciated heterogeneity between and within tendon cell populations. The atlas also serves as a resource to further the understanding of tendon extracellular matrix assembly and maintenance and in the design of therapies for tendinopathies.

The coating formation technique for artificial knee ligaments was proposed, which provided tight fixation of ligaments of polyethylene terephthalate (PET) fibers as a result of the healing of the bone channel in the short-term period after implantation. The coating is a frame structure of single-walled carbon nanotubes (SWCNT) in a collagen matrix, which is formed by layer-by-layer solidification of an aqueous dispersion of SWCNT with collagen during spin coating and controlled irradiation with IR radiation. Quantum mechanical method SCC DFTB, with a self-consistent charge, was used. It is based on the density functional theory and the tight-binding approximation. The method established the optimal temperature and time for the formation of the equilibrium configurations of the SWCNT/collagen type II complexes to ensure maximum binding energies between the nanotube and the collagen. The highest binding energies were observed in complexes with SWCNT nanometer diameter in comparison with subnanometer SWCNT. The coating had a porous structure&mdash, pore size was 0.5&mdash, 6 &mu, m. The process of reducing the mass and volume of the coating with the initial biodegradation of collagen after contact with blood plasma was demonstrated. This is proved by exceeding the intensity of the SWCNT peaks G and D after contact with the blood serum in the Raman spectrum and by decreasing the intensity of the main collagen bands in the SWCNT/collagen complex frame coating. The number of pores and their size increased to 20 &mu, m. The modification of the PET tape with the SWCNT/collagen coating allowed to increase its hydrophilicity by 1.7 times compared to the original PET fibers and by 1.3 times compared to the collagen coating. A reduced hemolysis level of the PET tape coated with SWCNT/collagen was achieved. The SWCNT/collagen coating provided 2.2 times less hemolysis than an uncoated PET implant. MicroCT showed the effective formation of new bone and dense connective tissue around the implant. A decrease in channel diameter from 2.5 to 1.7 mm was detected at three and, especially, six months after implantation of a PET tape with SWCNT/collagen coating. MicroCT allowed us to identify areas for histological sections, which demonstrated the favorable interaction of the PET tape with the surrounding tissues. In the case of using the PET tape coated with SWCNT/collagen, more active growth of connective tissue with mature collagen fibers in the area of implantation was observed than in the case of only collagen coating. The stimulating effect of SWCNT/collagen on the formation of bone trabeculae around and inside the PET tape was evident in three and six months after implantation. Thus, a PET tape with SWCNT/collagen coating has osteoconductivity as well as a high level of hydrophilicity and hemocompatibility.

This report describes the diagnostic process of a rare disorder in a Brazilian female child. The patient presented initially as a 7-year-old with multiple whitish submucosal nodules of a fibrous consistency in the lower lip, but with an inconclusive pathology report. When she turned 9 years of age, she presented with exacerbation of the original clinical findings, which then involved the upper lip, buccal mucosa, tongue and lingual frenulum. In addition, dermatological lesions were noted on the child’s limbs and face, as well as a hoarse voice. Histopathological examination of the buccal mucosa revealed dense connective tissue with hyaline foci, which were positive with periodic acid-Schiff (PAS) staining and resistant to diastase digestion. Clinical and histopathological findings led to the diagnosis of a rare genetic disease with fewer than 300 reported cases - lipoid proteinosis. Magnetic resonance imaging revealed calcium deposits in her amygdaloid region of the brain, and nasopharyngolaryngoscopy revealed lesions in her vocal cords. The patient currently is stable and under multidisciplinary follow-up, but no treatment has been recommended to date. Resumo Este relato descreve o processo diagnóstico de uma doença rara em uma criança brasileira do sexo feminino. A paciente, inicialmente com 7 anos de idade, apresentava múltiplos nódulos submucosos esbranquiçados, de consistência fibrosa, no lábio inferior, mas com um laudo patológico inconclusivo. Quando completou 9 anos de idade, ela apresentou exacerbação dos achados clínicos originais, que envolveram o lábio superior, mucosa bucal, língua e frênulo lingual. Além disso, lesões dermatológicas foram observadas nos membros e no rosto da criança, assim como rouquidão. O exame histopatológico da mucosa bucal revelou tecido conjuntivo denso com focos hialinos, que foram positivos com coloração periódica com ácido-Schiff (PAS) e resistente à digestão da diástase. Os achados clínicos e histopatológicos levaram ao diagnóstico de uma doença genética rara com menos de 300 casos relatados - proteinose lipoide. A ressonância magnética revelou depósitos de cálcio em amígdala cerebral e a nasofaringolaringoscopia revelou lesões em cordas vocais. Atualmente, a paciente está estável e em acompanhamento multidisciplinar, mas nenhum tratamento foi recomendado até o momento.

Objectives To reduce the number of false-positive diagnoses in the screening of women with extremely dense breasts using magnetic resonance imaging (MRI), we aimed to predict which BI-RADS 3 and BI-RADS 4 lesions are benign. For this purpose, we use computer-aided diagnosis (CAD) based on multiparametric assessment. Materials and methods Consecutive data were used from the first screening round of the DENSE (Dense Tissue and Early Breast Neoplasm Screening) trial. In this trial, asymptomatic women with a negative screening mammography and extremely dense breasts were screened using multiparametric MRI. In total, 4783 women, aged 50 to 75 years, enrolled and were screened in 8 participating hospitals between December 2011 and January 2016. In total, 525 lesions in 454 women were given a BI-RADS 3 (n = 202), 4 (n = 304), or 5 score (n = 19). Of these lesions, 444 were benign and 81 were malignant on histologic examination.The MRI protocol consisted of 5 different MRI sequences: T1-weighted imaging without fat suppression, diffusion-weighted imaging, T1-weighted contrast-enhanced images at high spatial resolution, T1-weighted contrast-enhanced images at high temporal resolution, and T2-weighted imaging. A machine-learning method was developed to predict, without deterioration of sensitivity, which of the BI-RADS 3- and BI-RADS 4-scored lesions are actually benign and could be prevented from being recalled. BI-RADS 5 lesions were only used for training, because the gain in preventing false-positive diagnoses is expected to be low in this group. The CAD consists of 2 stages: feature extraction and lesion classification. Two groups of features were extracted: the first based on all multiparametric sequences, the second based only on sequences that are typically used in abbreviated MRI protocols. In the first group, 49 features were used as candidate predictors: 46 were automatically calculated from the MRI scans, supplemented with 3 clinical features (age, body mass index, and BI-RADS score). In the second group, 36 image features and the same 3 clinical features were used. Each group was considered separately in a machine-learning model to differentiate between benign and malignant lesions. We developed a Ridge regression model using 10-fold cross validation. Performance of the models was analyzed using an accuracy measure curve and receiver-operating characteristic analysis. Results Of the total number of BI-RADS 3 and BI-RADS 4 lesions referred to additional MRI or biopsy, 425/487 (87.3%) were false-positive. The full multiparametric model classified 176 (41.5%) and the abbreviated-protocol model classified 111 (26.2%) of the 425 false-positive BI-RADS 3- and BI-RADS 4-scored lesions as benign without missing a malignant lesion.If the full multiparametric CAD had been used to aid in referral, recall for biopsy or repeat MRI could have been reduced from 425/487 (87.3%) to 311/487 (63.9%) lesions. For the abbreviated protocol, it could have been 376/487 (77.2%). Conclusions Dedicated multiparametric CAD of breast MRI for BI-RADS 3 and 4 lesions in screening of women with extremely dense breasts has the potential to reduce false-positive diagnoses and consequently to reduce the number of biopsies without missing cancers.

Purpose. To present long-term results of modified bleb-limiting conjunctivoplasty as a successful treatment for intractable bleb dysesthesia and to review the literature on the surgical management of dysesthetic bleb. Methods. Consecutive case series and literature review. We present four cases of surgically reduced painful blebs. Our technique consisted of the following steps: (1) conjunctival, radial incision to the bare sclera in the desired limit of the bleb; (2) suturing with buried, interrupted sutures at the nearest edge of the filtering bleb; (3) lower limbal peritomy including unwanted area of the extended bleb; (4) dissection and removal of the underlying fibrous tissue when present; (5) conjunctival and resorbable sutures. In addition, a systematic literature review was performed. Only reports presenting outcomes of surgical treatment of bleb dysesthesia after filtering procedure were included in review. Results. Four eyes were included consecutively in the study in a period of 4 years. On average, they developed circumferential bleb dysesthesia 9.3 ± 4.7 months after uneventful combined phacotrabeculectomy with Mitomycin C as primary procedure. Surgical reduction was decided after failure of lubricants in controlling ocular discomfort. Two cases showed a dense fibrous tissue beneath the conjunctiva that was excised to ensure filtration. In all cases, a rapid disappearance of symptoms with very good aesthetic and functional outcome was observed. After 12-month follow-up, patients remained asymptomatic and maintained intraocular pressure of 10.7 ± 1.2 mmHg without treatment. A systematic review of the literature obtained 15 eligible case series (n = 123) with rates of success within 46–100%, favoring less aggressive approaches to reduce bleb size. Conclusion. Bleb dysesthesia is a rare complication of filtering glaucoma surgery. This modified bleb-limiting conjunctivoplasty technique (with removal of subjacent fibrous tissue if present) is able to target the underlying etiology providing ocular discomfort relief while maintaining bleb function and may be considered as first-choice surgical treatment.

Sterile and decellularized allograft tendons are viable biomaterials used in reconstructive surgeries for dense connective tissue injuries. Established allograft processing techniques including gamma irradiation and sodium dodecyl sulfate (SDS) can affect tissue integrity. Supercritical carbon dioxide (SCCO2) represents a novel alternative that has the potential to decellularize and sterilize tendons with minimized exposure to denaturants, shortened treatment time, lack of toxic residues, and superior tissue penetration, and thus efficacy. This study attempted to develop a single-step hybrid decellularization and sterilization protocol for tendons that involved SCCO2 treatment with various chemical additives. The processed tendons were evaluated with mechanical testing, histology, scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy. Uniaxial mechanical testing showed that tendons treated with SCCO2 and additive NovaKillTM Gen2 and 0.1% SDS had significantly higher (p &lt, 0.05) ultimate tensile stress (UTS) and Young&rsquo, s modulus compared to gamma-irradiated and standard-SDS-treated tendons. This was corroborated by the ultrastructural intactness of SCCO2-treated tendons as examined by SEM and FTIR spectroscopy, which was not preserved in gamma-irradiated and standard SDS-treated tendons. However, complete decellularization was not achieved by the experimented SCCO2-SDS protocols used in this study. The present study therefore serves as a concrete starting point for development of an SCCO2-based combined sterilization and decellularization protocol for allograft tendons, where additive choice is to be optimized.

Although the transcription factor EGR1 is known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, it still has many fewer names than biological functions. A broad range of signals induce Egr1 gene expression via numerous regulatory elements identified in the Egr1 promoter. EGR1 is also the target of multiple post-translational modifications, which modulate EGR1 transcriptional activity. Despite the myriad regulators of Egr1 transcription and translation, and the numerous biological functions identified for EGR1, the literature reveals a recurring theme of EGR1 transcriptional activity in connective tissues, regulating genes related to the extracellular matrix. Egr1 is expressed in different connective tissues, such as tendon (a dense connective tissue), cartilage and bone (supportive connective tissues), and adipose tissue (a loose connective tissue). Egr1 is involved in the development, homeostasis, and healing processes of these tissues, mainly via the regulation of extracellular matrix. In addition, Egr1 is often involved in the abnormal production of extracellular matrix in fibrotic conditions, and Egr1 deletion is seen as a target for therapeutic strategies to fight fibrotic conditions. This generic EGR1 function in matrix regulation has little-explored implications but is potentially important for tendon repair.

The paper deals with the possibility of processing category 2 animal byproducts with a ferment preparation. We chose collagen-rich cattle lips and ears as the category 2 byproducts for our study. The selected samples were processed in the following sequence: fixation, rinsing with running water, densifying the samples, slicing into sections, dying sections, and enclosing the sections under cover glass. The pathohistomorphologic changes found in the control samples significantly differ both before the processing and after the use of the ferment preparation Protepsin, which caused destructive metabolic and hydrolytic processes in the dense connective tissue of the ear and lip framework and led to softening of the muscle parenchyma of the organs.

Background: Squamous cell lung carcinoma (SqCLC) is a type of non-small-cell lung cancer, accounting for 25–30% of all lung cancer cases with a median advanced stage survival of 8–11 months. Here we present a rare case of long-term survival with metastatic SqCLC following coil embolisation of the right pulmonary artery. Case presentation: The 49-year-old patient was diagnosed with stage IV (cT4N3M1) SqCLC in 2007 due to a biopsy-proven central malignant tumour in the right lung and bilateral mediastinal lymphadenopathy. A magnetic resonance imaging scan also revealed a metastatic lesion in the liver. Soon after the diagnosis, the patient experienced pulmonary haemorrhage, which was managed by obturating the intermediate bronchus and performing coil embolisation of the right pulmonary artery. The patient also received chemotherapy in 2007 and 2009 without radiological changes. At three different time points in years 2010–2019, biopsies of the primary tumour were taken. All showed dense connective tissue with no indication of cancer growth. In 2020, a positron emission tomography scan showed no pathological metabolic activity in the lungs and liver. Currently, the patient remains in a stable clinical condition with a good performance status. Conclusion: The long-term clinical benefit indicates a direct effect of coil embolisation on tumour progression. We suggest that coil embolisation of tumour-feeding arteries could be considered as a potential treatment method for patients with SqCLC.

Aim of the study was to investigate the atherosclerotic calcification employing our original technique of tissue staining, embedding, and backscattered scanning electron microscopy. Materials and methods . Atherosclerotic plaques excised during the carotid endarterectomy have been fixed in 10 % neutral phosphate buffered saline formalin for 24 hours, stained in 2 % osmium tetroxide for 60 hours and in alcoholic uranyl acetate for 5 hours with the subsequent epoxy resin embedding, grinding, polishing, lead citrate counterstaining for 7 minutes, sputter coating with carbon and backscattered scanning electron microscopy. We then analysed localisation, structure, and microenvironment of the calcium deposits. Results . Within the atherosclerotic plaques, we identified 3 distinct calcification morphologies: compact homogenous macrocalcifications, sheet-like heterogeneous macrocalcifications along the destructed collagen and elastin fibers, and microcalcifications around large calcium deposits with the sharp margins. However, even relatively homogenous compact macrocalcifications had uneven distribution of electron density. In conjunction with groups of mineral deposits of distinct calcium phosphate phases including nascent calcified loci, this testified to ongoing calcium phosphate maturation while multiple microcalcifications merging into the single macrocalcification indicated ossification. Compact ossifying macrocalcifications with smooth margins frequently had a dense connective tissue capsule. The microenvironment of calcium deposits was often characterised by leaky neovessels. Conclusion . Diversity of calcification morphologies and ossification in atherosclerotic plaques is similar to those observed in calcific aortic valve disease and bioprosthetic heart valve failure. Combined with atherosclerotic plaque disaggregation followed by flow cytometry and singlecell RNA sequencing, our technique may improve our understanding of atherosclerotic calcification and lead to the identification of appropriate therapeutic targets to prevent or retard this process.

ObjectiveTo assess the feasibility of using tissue sound speed as a quantitative marker of breast density.MethodsThis study was carried out under an Institutional Review Board–approved protocol (written consent required). Imaging data were selected retrospectively based on the availability of US tomography (UST) exams, screening mammograms with volumetric breast density data, patient age of 18 to 80 years, and weight less than 300 lbs. Sound speed images from the UST exams were used to measure the volume of dense tissue, the volume averaged sound speed (VASS), and the percent of high sound speed tissue (PHSST). The mammographic breast density and volume of dense tissue were estimated with three-dimensional (3D) software. Differences in volumes were assessed with paired t-tests. Spearman correlation coefficients were calculated to determine the strength of the correlations between the mammographic and UST assessments of breast density.ResultsA total of 100 UST and 3D mammographic data sets met the selection criteria. The resulting measurements showed that UST measured a more than 2-fold larger volume of dense tissue compared to mammography. The differences were statistically significant (P < 0.001). A strong correlation of rS = 0.85 (95% CI: 0.79–0.90) between 3D mammographic breast density (BD) and the VASS was noted. This correlation is significantly stronger than those reported in previous two-dimensional studies (rS = 0.85 vs rS = 0.71). A similar correlation was found for PHSST and mammographic BD with rS = 0.86 (95% CI: 0.80–0.90).ConclusionThe strong correlations between UST parameters and 3D mammographic BD suggest that breast sound speed should be further studied as a potential new marker for inclusion in clinical risk models.

Relevance. The number of ventral hernias recurrence after abdominal wall endoprosthetics with the lightweight endoprosthesis is 8-10%. The purpose of the research is to study the morphological changes of the connective tissue, surrounding a lightweight polypropylene endoprosthesis, at the early stages of implantation at the use of platelet-rich autoplasma. Materials and methods. The results of experimental research of the course of wound process in the abdominal wall tissues during the implantation of the lightweight polypropylene prosthesis on 50 Chinchilla rabbits divided into 2 groups of 25 animal units each have been analyzed. Subaponeurotic implantation of the prosthesis was carried out in the first group of animals. In the second group, the platelet-rich autoplasma was twice introduced after the implantation of the prosthesis during surgery and on the third day of the postoperative period at the rate of 0,5 ml plasma per 1 cm2 of the endoprosthesis. The animals were taken away from the experiment on the 3rd, 7th, 10th, 14th and 21st day. Morphometric and histological study of reactive changes of tissue surrounding the implanted endoprosthesis was carried out. Results and its discussion. In the animals of the second group, the inflammatory response to prosthesis implantation was 1,3 times lower on the third day, 1,2 times lower on the 7th day, and 1,1 times lower on the 10th day, than in the first group. Fibroblastic response, on the contrary, has increased into 1,2 times on the third day, into 1,14 during the 7th day and into 1,18 during the 14th day after the introduction of autoplasma. The thickness of the connective tissue capsule in the second group was 1,57 times higher than in the first group on the 21st day of the experiment. At this time, in the first group, the immature connective tissue capsule has been represented by the loose collagen fibers and fibroblastic cells without separation into the layers. In the second group, a dense connective tissue frame has been formed by the mature collagen fibers arranged compactly and in parallel to each other. The layer-by-layer structure of the capsule is well expressed: the inner layer consists of the fibroblastic cells, and the outer layer consists of the mature collagen fibers. Conclusion. The use of platelet-rich plasma to stimulate reparative processes in the implantation of the lightweight polypropylene prosthesis in the abdominal wall is pathogenetically justified and effective.