Endotypes of Chronic Rhinosinusitis with Primary and Recurring Nasal Polyps in the Latvian Population.

Chronic rhinosinusitis (CRS) is a complex syndrome with various inflammatory mechanisms resulting in different patterns of inflammation that correlate with the clinical phenotypes of CRS. Our aim was to use detected IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, Ki 67, HBD-2, HBD-3, and LL-37 to classify specific inflammatory endotypes in chronic rhinosinusitis with the tissue of nasal polyps (CRSwNP). Samples from 35 individuals with primary and recurrent CRSwNP were taken during surgery. The tissues were stained for the previously mentioned biomarkers immunohistochemically. A hierarchical cluster analysis was performed. The clinical parameters were compared between clusters. Five clusters had significantly different biomarkers between groups. There were no significant differences in the clinical parameters, except for the Lund-Mackay score, which was significantly higher in cluster 4 compared to that of cluster 1 (p = 0.024). Five endotypes of (CRSwNP) are characterized by different combinations of type 1, type 2, and type 3 tissue inflammation patterns. In the Latvian population, endotypes associated with neutrophilic inflammation or a combination of neutrophilic inflammation and type 2 inflammation are predominant. Increased proliferation marker Ki 67 values are not associated with more severe inflammation in the tissue samples of chronic rhinosinusitis with nasal polyps.

Characterization of Angiogenic, Matrix Remodeling, and Antimicrobial Factors in Preterm and Full-Term Human Umbilical Cords.

BACKGROUND: Little is known about morphogenetic changes in the umbilical cord during the maturation process. Extracellular matrix remodeling, angiogenesis, progenitor activity, and immunomodulation are represented by specific markers; therefore, the aim of this study was to determine the expression of matrix metalloproteinase-2 (MMP2), tissue inhibitor of metalloproteinases-2 (TIMP2), CD34, vascular endothelial growth factor (VEGF), and human ß-defensin 2 (HBD2) in preterm and full-term human umbilical cord tissue. METHODS: Samples of umbilical cord tissue were obtained from 17 patients and divided into two groups: very preterm and moderate preterm birth umbilical cords; late preterm birth and full-term birth umbilical cords. Routine histology examination was conducted. Marker-positive cells were detected using the immunohistochemistry method. The number of positive structures was counted semi-quantitatively using microscopy. Statistical analysis was carried out using the SPSS Statistics 29 program. RESULTS: Extraembryonic mesenchyme cells are the most active cell producers, expressing MMP2, TIMP2, VEGF, and HBD2 at notable levels in preterm and full-term umbilical cord tissue. Statistically significant differences in the expression of CD34, MMP2, and TIMP2 between the two patient groups were found. The expression of VEGF was similar in both patient groups, with the highest number of VEGF-positive cells seen in the extraembryonic mesenchyme. The expression of HBD2 was the highest in the extraembryonic mesenchyme and the amniotic epithelium, where mostly moderate numbers of HBD2-positive cells were detected. CONCLUSIONS: Extracellular matrix remodeling in preterm and term umbilical cords is strongly regulated, and tissue factors MMP2 and TIMP2 take part in this process. The expression of VEGF is not affected by the umbilical cord's age; however, individual patient factors can affect the production of VEGF. Numerous CD34-positive cells in the endothelium of the umbilical arteries suggest a significant role of progenitor cells in very preterm and moderate preterm birth umbilical cords. Antimicrobial activity provided by HBD2 is essential and constant in preterm and full-term umbilical cords.

Comparison of Tissue Factors in the Ontogenetic Aspects of Human Cholesteatoma.

BACKGROUND: An acquired cholesteatoma is a benign but locally aggressive lesion in the middle ear. It is characterized by chronic inflammation and the destruction of surrounding bone. Therefore, the aim of this study was to compare defensins HßD-2 and HßD-4; pro- and anti-inflammatory cytokines IL-1α and IL-10; proliferation marker Ki-67; transcription factor NF-κß; angiogenetic factor VEGF; Sonic hedgehog gene protein SHH; and remodeling factors MMP-2, MMP-9, TIMP-2, and TIMP-4 in adult and pediatric cholesteatoma tissue, and to compare these groups with control skin tissue. METHODS: The study included 25 cholesteatoma tissue material samples from children, 25 from adults, and 7 deep external ear canal skin samples from cadavers. The tissues were stained immunohistochemically and evaluated using semi-quantitative methods. Nonparametric tests, such as the Kruskal-Wallis test and Spearman rank correlation, were used. RESULTS: There were no statistically discernible differences between the adult and children groups when comparing the relative numbers of factor-positive cells. CONCLUSIONS: There are no histopathological differences between adult and children cholesteatoma tissues.

Distribution and appearance of myosin, dystrophin, and collagen IV in strabismus-affected extraocular muscle tissue compared with control tissue.

OBJECTIVE: Extraocular muscles have complex development processes. The present study aimed to analyze the presence of myosin, dystrophin, and collagen IV in the strabismus-affected extraocular muscle. METHODS: This research was an observational case-control study. Myosin, dystrophin, and collagen IV were detected by histological and immunohistochemical analyses of extraocular muscle samples from concomitant strabismus patients and controls. A semi-quantitative grading method and statistical analysis were used. RESULTS: In the strabismus-affected extraocular muscle, morphological analysis demonstrated different-sized muscle fibers. Immature muscle fibers and an increased amount of connective tissue were also noted. Strong positive correlations were identified between myosin and collagen IV and between dystrophin and collagen IV. CONCLUSIONS: The presence of newly formed muscle fibers, increased connective tissue, and variable diameters of skeletal striated muscle fibers indicate the decreased quality of extraocular muscles in strabismus cases. Reduced levels of myosin and dystrophin and a near absence of collagen IV in strabismus-affected skeletal striated muscle fibers characterized the muscular dystrophy of strabismus. Adjuvant therapy aimed at normalizing the metabolism of these muscles may be appropriate alongside concomitant strabismus treatment.

Automatization of CT Annotation: Combining AI Efficiency with Expert Precision.

The integration of artificial intelligence (AI), particularly through machine learning (ML) and deep learning (DL) algorithms, marks a transformative progression in medical imaging diagnostics. This technical note elucidates a novel methodology for semantic segmentation of the vertebral column in CT scans, exemplified by a dataset of 250 patients from Riga East Clinical University Hospital. Our approach centers on the accurate identification and labeling of individual vertebrae, ranging from C1 to the sacrum-coccyx complex. Patient selection was meticulously conducted, ensuring demographic balance in age and sex, and excluding scans with significant vertebral abnormalities to reduce confounding variables. This strategic selection bolstered the representativeness of our sample, thereby enhancing the external validity of our findings. Our workflow streamlined the segmentation process by eliminating the need for volume stitching, aligning seamlessly with the methodology we present. By leveraging AI, we have introduced a semi-automated annotation system that enables initial data labeling even by individuals without medical expertise. This phase is complemented by thorough manual validation against established anatomical standards, significantly reducing the time traditionally required for segmentation. This dual approach not only conserves resources but also expedites project timelines. While this method significantly advances radiological data annotation, it is not devoid of challenges, such as the necessity for manual validation by anatomically skilled personnel and reliance on specialized GPU hardware. Nonetheless, our methodology represents a substantial leap forward in medical data semantic segmentation, highlighting the potential of AI-driven approaches to revolutionize clinical and research practices in radiology.

The presence and distribution of various genes in postnatal CLP-affected palatine tissue.

BACKGROUND: Worldwide cleft lip with or without a cleft palate (CL/P) is the most common craniofacial birth defect. Apart from changes in facial appearance, additionally affected individuals often suffer from various associated comorbidities requiring complex multidisciplinary treatment with overall high expenses. Understanding the complete pathogenetic mechanisms of CL/P might aid in developing new preventative strategies and therapeutic approaches, help with genetic counselling, and improve quality of life. Many genes have been associated with the development of orofacial clefts; however, the majority require further research. Based on the role of PAX7, PAX9, SHH, SOX3, WNT3A, and WNT9B in orofacial development, the intention was to use chromogenic in situ hybridization to detect the six genes in postnatal CLP-affected palatine tissue and compare their distribution within the tissue samples. RESULTS: Statistically significant differences in the distribution of PAX7, PAX9, WNT3A, and WNT9B were observed. In total, 19 pairs of moderate to very strong positive correlations were noted. CONCLUSIONS: Changes in the cleft-affected palatine epithelium primarily seem to be associated with the PAX7 gene; however, PAX9, WNT3A, WNT9B, and SOX3 role seems to be more limited. Whilst connective tissue changes seem to depend on PAX7 only, SHH seems to participate individually and indistinctly. Numerous positive correlations reflect the complicating interactions of the pathways and their components in the orofacial cleft morphopathogenesis.

Assessment of professional singers using laryngeal, respiratory, and airflow measurements.

PURPOSE: In the pedagogy of classical vocal singing, it can be difficult to determine the human voice fach, especially for the voice of aspiring vocalists. Hence, an objective metric-based system for the determination of the human voice is needed. In the present study, we investigated the anthropological and aerodynamic parameters for 60 professional singers with a professionally confirmed singing range. METHODS: Amongst the 60 included professional singers, there were ten participants each for sopranos, mezzo-sopranos, altos (female vocal fach), and tenors, baritones, basses (male vocal fach). Airflow measurements were recorded using spirometry whilst anthropological measurements were taken using CT scans. Appropriate statistical analyses were done using the Mann-Whitney U test and Kruskal Wallis H test with post-hoc tests and Bonferroni correction. p < 0.05 was considered statistically significant. RESULTS: Soprano singers, who have the highest pitch, were found to be the shortest and least heavy, whilst basses, who have the lowest pitch, were found to be tallest and heaviest amongst the study participants. Furthermore, sopranos had the smallest lung volumes while the basses had the largest lung volumes (raw spirometry measures). However, when normalized ratios were considered, no differences were observed. Finally, laryngeal size showed sexual dimorphism due to developmental changes. CONCLUSIONS: A mix of anthropological and aerodynamic measurements may be useful to assist singers and vocal pedagogues to assess and determine voice types before the beginning of their vocal studies.

Medical education in Latvia: an overview of current practices and systems.

Located in northern Europe, Latvia is one of the three Baltic States with a population of 1.9 million. The country has a rich history of medical education spanning a century and is becoming an emerging global hub for medical education. Although the surge in international students has been beneficial for the development of educational and research infrastructure, increasing demands from local students, along with institutional capacity constraints, have overburdened the available resources. Substantial investments are being made to adapt to the rapidly changing geopolitical and techno-biomedical landscape. This perspective paper presents an overview of the country's medical education system, its challenges, and prospects from pre-university to doctoral level.

Antimicrobial Peptides and Interleukins in Cleft Soft Palate.

Cleft palate is one of the most common and well-studied congenital anomalies; however, the role of protective tissue factors in its pathophysiology is still debated. The aim of our study was to evaluate interleukin and antimicrobial peptide appearance and distribution in cleft palate. Eight soft palate samples were obtained during veloplasty procedures. Immunohistochemical staining was applied to detect HBD-2-, HBD-3-, HBD-4-, LL-37-, IL-10-, and CD-163-positive cells via light microscopy. For statistical evaluation, the Mann-Whitney U test and Spearman's rank correlation coefficient were used. A significant difference between study groups was observed for HBD-2 and IL-10 in epithelial and connective tissue as well as HBD-4 in connective tissue. The number of HBD-3-positive cells was moderate in the patients, and few were observed in the controls. The number of LL-37-positive cells varied from a moderate amount to a numerous amount in both study groups, whilst CD-163 marked a moderate number of positive cells in patients, and a few-to-moderate amount was observed in the controls. Numerous correlations between studied factors were revealed in cleft tissues. The increase in antimicrobial peptides HBD-2 and HBD-4 and anti-inflammatory cytokine IL-10 suggested a wide compensatory elevation of the local immune system against cleft-raised tissue changes. The correlations between the studied factors (HBD-2, HBD-3, HBD-4, LL-37, and IL-10) proved the synergistic involvement of common local defense factors in postnatal cleft palate morphopathogenesis.

Antimicrobial and Defense Proteins in Chronic Rhinosinusitis with Nasal Polyps.

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) presently remains a difficult disease to manage. Antimicrobial and defense proteins are important factors that could help characterize the role of microorganisms in CRSwNP pathogenesis, as the concept of microbial dysbiosis in CRS is still being considered. Our aim is to investigate the complex appearance, relative distribution and interlinks of human ß defensin 2 (HBD-2), human ß defensin 3 (HBD-3), human ß defensin 4 (HBD-4), and cathelicidin LL 37 (LL 37) in chronic rhinosinusitis with nasal polyps (CRSwNP)-affected human nasal mucosa. Materials and Methods: The study group consisted of 48 samples from patients with CRSwNP. Samples were collected during functional endoscopic sinus surgery. The control group consisted of 17 normal healthy nasal mucosa samples gathered during routine septoplasty. ß-defensin-2, ß-defensin-3, ß-defensin-4 and cathelicidin LL 37 in tissue were detected via immunohistochemical analysis. Results: HBD-2, HBD-3 and LL 37 were significantly decreased in epithelial cells in both primary and recurrent nasal polyp samples (p < 0.001) in comparison to control samples. HBD-2 was decreased in the subepithelial connective tissue of primary nasal polyp samples when compared to both recurrent polyp (p = 0.050) and control (p = 0.033) samples. In subepithelial connective tissue, significantly more HBD-3-positive structures were observed in primary nasal polyp samples (p = 0.049) than in control samples. In primary polyp samples, moderate correlations between connective tissue HBD-3 and connective (R = 0.584, p = 0.001) and epithelial tissue LL 37 (R = 0.556, p = 0.002) were observed. Conclusions: Decreased HBD-2, HBD-3 and LL 37 concentrations in the epithelium suggest a dysfunction of the epithelial barrier in patients with nasal polyps. Decreased subepithelial connective tissue HBD-2 suggests different responses to nasal microbiota in patients with primary nasal polyps compared to recurrent nasal polyps. Increased HBD-3 in subepithelial connective tissue suggests a possible role of this antimicrobial peptide in the pathogenesis of primary nasal polyps.

Characterization of SHH, SOX3, WNT3A and WNT9B Proteins in Human Non-Syndromic Cleft Lip and Palate Tissue.

Orofacial clefts have been associated with specific cleft candidate genes which encode regulatory proteins required for orofacial region development. Cleft candidate genes encode proteins involved with the cleft morphopathogenesis process, but their exact interactions and roles are relatively unclear in human cleft tissue. This study evaluates the presence and correlations of Sonic Hedgehog (SHH), SRY-Box Transcription Factor 3 (SOX3), Wingless-type Family Member 3A (WNT3A) and 9B (WNT9B) protein containing cells in different cleft tissue. Non-syndromic cleft-affected tissue was subdivided into three groups-unilateral cleft lip (UCL) (n = 36), bilateral cleft lip (BCL) (n = 13), cleft palate (CP) (n = 26). Control tissue was obtained from five individuals. Immunohistochemistry was implemented. The semi-quantitative method was used. Non-parametric statistical methods were applied. A significant decrease in SHH was found in BCL and CP tissue. SOX3, WNT3A and WNT9B had a significant decrease in all clefts. Statistically significant correlations were found. The significant decrease in SHH could be associated with BCL and CP pathogenesis. SOX3, WNT3A and WNT9B could have morphopathogenetic involvement in UCL, BCL, and CP. Similar correlations imply the presence of similar pathogenetic mechanisms in different cleft variations.

Morphopathogenesis of Adult Acquired Cholesteatoma.

Background and Objectives. The aim of this study was to compare the distribution of proliferation markers (Ki-67, NF-κß), tissue-remodeling factors (MMP-2, MMP-9, TIMP-2, TIMP-4), vascular endothelial growth factor (VEGF), interleukins (IL-1 and IL-10), human beta defensins (HßD-2 and HßD-4) and Sonic hedgehog gene protein in cholesteatoma and control skin. Methods. Nineteen patient cholesteatoma tissues and seven control skin materials from cadavers were included in the study and stained immunohistochemically. Results. Statistically discernible differences were found between the following: the Ki-67 in the matrix and the Ki-67 in the skin epithelium (p = 0.000); the Ki-67 in the perimatrix and the Ki-67 in the connective tissue (p = 0.010); the NF-κß in the cholesteatoma matrix and the NF-κß in the epithelium (p = 0.001); the MMP-9 in the matrix and the MMP-9 in the epithelium (p = 0.008); the HßD-2 in the perimatrix and the HßD-2 in the connective tissue (p = 0.004); and the Shh in the cholesteatoma's perimatrix and the Shh in the skin's connective tissue (p = 0.000). Conclusion. The elevation of Ki-67 and NF-κß suggests the induction of cellular proliferation in the cholesteatoma. Intercorrelations between VEGF, NF-κß and TIMP-2 induce neo-angiogenesis in adult cholesteatoma. The similarity in the expression of IL-1 and IL-10 suggests the dysregulation of the local immune status in cholesteatoma. The overexpression of the Sonic hedgehog gene protein in the cholesteatoma proves the selective local stimulation of perimatrix development.

Temporomandibular Joint Ankylosis in a Girl Child: Immunochemical Evaluation of Tissue Material Obtained from Repeated Arthroplasty Surgeries.

Temporomandibular joint ankylosis (TMJA) is a rare, but debilitating, condition that leads to TMJ joint hypomobility. Surgery is the mainstay for treatment, which is accompanied by rehabilitative and psychological support. Despite the advances in surgical techniques, the recurrence of TMJA post-surgery has been reported as a common complication. Therefore, it becomes essential to investigate and understand the histo-morpho-pathological processes governing these ankylotic changes. Given the lack of such studies in the literature, herein we present a case of a girl child who underwent primary surgery at the age of six years, followed by a second surgery at the age of twelve years. Ankylotic tissue samples collected during both surgeries were studied using various immunohistochemical markers for tissue remodeling, inflammation, antimicrobial activity, and transcriptional regulation. The expression of MMP-2 and -9 was downregulated in repeated surgery materials, whilst MMP-13 was rarely detected in both tissues. Strong MMP-8, TIMP-2, and TIMP-4 expressions were noted in both tissues, showing their anti-inflammatory and protective roles. Moderately strong expression of bFGF, FGFR-1, IL-1α, and TNF-α could indicate sustained tissue growth in the background of inflammation (wound healing). Interestingly, the expression of ß-defensin-2 was found to be constant in both tissues, thereby indicating possible ECM remodeling and collagen breakdown. Finally, a moderate expression of RUNX-2, coupled with a low expression of WNT-1 and -3a, could indicate a slow and delayed bone regeneration process. Our results showcase the complex myriad of pathways that could be involved in the progression of TMJA and post-surgery healing processes. Immunopathological studies could aid in improving the diagnosis, treatment, and prognosis for patients affected with TMJA.

Local Defense Factors in Cleft-Affected Palate in Children before and during Milk Dentition Age: A Pilot Study.

One of the most frequent congenital orofacial defects is the cleft lip and palate. Local tissue defense factors are known to be important in immune response and inflammatory and healing processes in the cleft tissue; however, they have only been researched in older children during mixed dentition. Thus, the aim of this study is to assess the distribution of LL-37, CD-163, IL-10, HBD-2, HBD-3, and HBD-4 in children before and during milk dentition. The unique and rare material of palate tissue was obtained from 13 patients during veloplastic surgeries during the time span of 20 years. Immunohistochemistry, light microscopy, semi-quantitative evaluation, and non-parametric statistical analysis were used. A significant decrease in HBD-3 and HBD-4 in the connective tissue was found, as well as several mutual statistically significant and strong correlations between HBD-2, HBD-3, HBD-4, and LL-37. Deficiency of HBD-3 and HBD-4 suggests promotion of chronic inflammation. The scarcity of HBD-4 could be connected to the different signaling pathways of dental pulp cells. Mutual correlations imply changes in the epithelial barrier, amplified healing efficiency, and increased antibacterial line of defense. Deprivation of changes in IL-10 quantity points to possible suppression of the factor. The presence of similar CD-163 immunoreactive substances produced by M2 macrophages was also observed.

Evaluation of the Multiple Tissue Factors in the Cartilage of Primary and Secondary Rhinoplasty in Cleft Lip and Palate Patients.

Cleft lip and palate (CLP) is one of the craniofacial defects. The objective of this study was to identify the differences in appearance between the tissue factors in cartilage of CLP patients after primary and secondary rhinoplasty. Immunohistochemistry was performed with MMP-2, MMP-8, MMP-9, TIMP-2, IL-1α, IL-10, bFGF, and TGFß1. The quantification of the structures was performed using a semi-quantitative census method. MMP-2, -9, IL-1a, and bFGF demonstrated higher number of positive cells in patients, while the number of MMP-8, IL-1a, -10 and TGFß1 cells was higher or equal in the control subjects. The only statistically significant difference between CLP-operated patients was found in the TIMP-2 group, where the primary CLP patient group had a higher number of TIMP-2 positive chondrocytes than the secondary CLP patient group (U = 53.5; p = 0.021). The median value of the primary CLP group was ++ number of TIMP-2 positive chondrocytes compared to +++ in the secondary CLP group. No statistically significant difference was found between primary and secondary rhinoplasty patients for other tissue factors. Commonly, the rich expression of different tissue factors suggests a stimulation of higher elasticity in cleft affected cartilage. The statistically significant TIMP-2 elevation in primary operated cartilage indicates an impact of the selective tissue remodeling for hard tissue.

Characterization of Cytokines and Proliferation Marker Ki-67 in Chronic Rhinosinusitis with Recurring Nasal Polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammation of the mucosa of the nose and paranasal sinuses with the presence of polyps, affecting between 2.7% and 4.4% of the population. Cytokine analysis has become important in research on inflammatory mechanisms in CRSwNP. Therefore, our aim is to investigate the complex appearance, relative distribution, and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, and Ki-67 in CRSwNP. METHODS: Samples of nasal polyps were obtained from 19 patients with previously diagnosed CRSwNP and the recurrence of polyps after previous surgeries. The control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviations. Tissues were stained for previously mentioned cytokines and Ki-67 immunohistochemically. RESULTS: Polyp samples showed an increased presence of cytokines in subepithelial connective tissue and a decreased appearance in epithelium when compared to controls. There were several very strong, strong, and moderate correlations among factors. CONCLUSIONS: IL-6 strongly correlates with other cytokines as well as with the proliferation marker Ki-67, which suggests significant stimulation of this regulatory cytokine and its possible involvement in the pathogenesis of recurrent nasal polyps. IL-4, IL-7, IL-10, and IL-12 correlate with Ki-67, which suggests the possible involvement of these cytokines in tissue cell proliferation in the case of recurrent nasal polyps.

Glycosaminoglycan, Antimicrobial Defence Molecule and Cytokine Appearance in Tracheal Hyaline Cartilage of Healthy Humans.

Hyaline cartilage is an important tracheal structure, yet little is known about its molecular composition, complicating investigation of pathologies and replacement options. Our aim was to research tracheal hyaline cartilage structure, protective tissue factors and variations in healthy humans. The tissue material was obtained from 10 cadavers obtained from the Riga Stradins University Institute of Anatomy and Anthropology archive. Tissues were stained with Bismarck brown and PAS for glycosaminoglycans, and immunohistochemistry was performed for HBD-2, HBD-3, HBD-4, IL-10 and LL-37. The slides were inspected by light microscopy and Spearman's rank correlation coefficient was calculated. The extracellular matrix was positive across hyaline cartilage for PAS, yet Bismarck brown marked positive proliferation and growth zones. Numerous positive cells for both factors were found in all zones. All of the antimicrobial defence molecules and cytokines were found in a moderate number of cells, except in the mature cell zone with few positive cells. Spearman's rank correlation coefficient revealed strong and moderate correlations between studied factors. Hyaline cartilage is a tracheal defence structure with a moderate number of antimicrobial defence protein and cytokine immunoreactive cells as well as numerous glycosaminoglycan positive cells. The extracellular matrix glycosaminoglycans provide structural scaffolding and intercellular signalling. The correlations between the studied factors confirm the synergistic activity of them.

Remodeling Factors, Transcription Factors and Angiogenetic Factors in Cholesteatoma in Ontogenetic Aspect.

Introduction: The main goal of our study was to describe the transcription factor (NF-κß), angiogenetic factor (VEGF), and remodeling markers (MMP-9 and TIMP-4) of the cholesteatoma tissue compared to control skin tissue. There are still uncertainties how transcription, angiogenetic and remodeling factors affect the cholesteatoma course. Materials and Methods: Eight cholesteatoma tissue specimens were retrieved from children, seven - from adults, seven skin controls - from cadavers. Obtained material immunohistochemically were stained for NF-κß, MMP-9, TIMP-4, VEGF. Non-parametric statistic methods were used. Results: A statistically significant higher numbers of NF-κß and TIMP-4 immunoreactive cells in the cholesteatoma compared to control group. A very strong positive correlation between MMP-9 and TIMP-4 was seen in the patient group. A strong positive correlation - between MMP-9 in matrix and MMP-9, VEGF in perimatrix, between TIMP-4 in matrix and TIMP-4 in perimatrix, NF-κß in the matrix and VEGF; between TIMP-4 in perimatrix and NF-κß in the matrix. Conclusions: Correlation between MMP-9 and TIMP-4 suggests that TIMP-4 in cholesteatoma tissue intercorrelates to MMP-9. TIMP-4 likely regulates the development of cholesteatoma. Disbalance between MMPs and TIMPs affects NF-κß and causes uncontrolled cell proliferation and immune response in this tumor. There is a lack of VEGF strong expression in cholesteatoma perimatrix.

Epidermoid cyst of the facial skin: an investigative case report.

Orofacial epidermoid cysts are rare entities that present as encapsulated, subepidermal painless masses, usually slow growing and asymptomatic. They are mostly limited to the floor of the mouth, tongue, lips, palate or jaws. Herein, we present an atypical case of epidermoid cyst originating from the left cheek facial epidermis in a 27-year-old male patient. The cyst presented as a swelling that was slowly progressing in size since the past 1 year with no discharge. Complete excision of the mass was done, and the cyst cavity was found to be filled with a cheesy-white, granular, semi-solid proteinaceous exudate which completely occluded the punctum. The patient post-operatively revealed persistent mechanical trauma due to incorrect workplace habits he developed, which led to the formation of the epidermoid cyst. Patient education was done and was advised to use proper workplace instrumentation.