Influence of tumor topography on clinical-morphological profile of laryngeal malignancies.

AIM: Laryngeal cancers are redoubtable because they are still diagnosed in advanced stages which results in poor survival and the decline of life quality. The authors intend to identify if the tumor topography influences clinical behavior, the morphological profile and therapeutic strategy. PATIENTS, MATERIALS AND METHODS: The study group included 188 patients with laryngeal malignancies diagnosed and treated in an Ear, Nose and Throat (ENT) Department. The patients have been divided into four groups according to the tumor topography and extension. Three categories of parameters were defined (epidemiological, clinical, and morphological) and analyzed comparatively between the four groups using filter scales and the χ² (chi-squared) correlation test. RESULTS: Epidemiological parameters (sex, age, socio-economic status) showed no significant differences between the four groups. Clinical parameters (symptoms, lymphadenopathies, surgical procedures, and hospitalization) instead registered significant differences between the four groups. Morphological parameters (longitudinal diameter, transverse diameter, shape, gross aspect, histopathological aspect, grade, local invasion - pT, lymph node invasion - pN, metastases - pM and tumor stage), excepting shape, registered too significant differences between the four groups. The analysis of the whole set of parameters in each group revealed different, distinct profiles for each of the topographic groups, especially for glottic and large tumors. Our results concerning the entire series of tumors ranged in the limits of variation of each of the parameters observed in the literature. CONCLUSIONS: Our study revealed that tumors placed in different regions of the larynx have distinct profiles from epidemiological, clinical, and morphological points of view. However, the profile of our entire group of tumors proved to be comparable with the literature data.

Multicenter Epidemiological Study of Nosebleeds Requiring Hospitalization.

Epistaxis is a common presenting symptom either emergency condition or ambulatory in Otorhinolaryngology, affecting people of all ages. A multicentric retrospective descriptive study of 380 patients who were hospitalized with epistaxis over a 3.8 year period was carried out. Data collected was analyzed using IBM SPSS Statistics 25 and illustrated using Microsoft Office/Word 2016. The current study showed that male adults after 60 years old are most affected by nasal bleeding. More than half of hospitalized patients have severe epistaxis at the time of hospitalization. However, further studies are necessary to be done in order to fully elucidate the epidemiology of nosebleeds requiring hospitalization.

Etiological Profile of Epistaxis: Pre-Pandemic Versus Pandemic.

Nosebleed or epistaxis is one of the most common forms of presenting an emergency in the ENT field. Since March 11, 2020, the World Health Organisation has proclaimed COVID-19 a global pandemic, and the world has been closed down. The main objective of the study is to analyse and compare the dynamics of epistaxis aetiology among the cases that required hospitalisation in the pre-pandemic period and the period of the COVID 19 pandemic. The study is multicenter retrospective from October 2018 to May 2022, including 380 cases of hospitalised epistaxis, with the mention that March 2020 is considered the beginning of the pandemic period. 60.8% of the patients enrolled in the study in the pre-pandemic period (60.8%) and 39.2% in the pandemic period. Differences between groups were not statistically significant between study entries (pre-pandemic vs. pandemic) and age (p=0.331), gender (p=0.916) or existence of local causes for epistaxis (p=0.895). Patients with general causes for epistaxis were more frequently enrolled in the pandemic period, while patients without general causes for epistaxis were more frequently enrolled in the pre-pandemic period. Patients with a hospitalisation period of more than 5 days were more frequently enrolled in the pre-pandemic period while patients with a hospitalisation period of 3 to 5 days were more frequently enrolled in the pandemic period. Also, patients with idiopathic epistaxis were more frequently enrolled in the pre-pandemic period. Based on the results presented in our study, the period of the Covid 19 pandemic directly influenced both the number of patients and the period of hospitalisation.

Current approach of juvenile nasopharyngeal angiofibroma: a case series.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor that affects predominantly males and is known by its highly vascular character. We have performed a 3-year retrospective study of patients with JNA surgically treated within the third ENT Department of Prof. Dr. Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania. In all the cases, the patients were investigated both clinically and through medical imaging before surgery and all tumors were embolized. Our study comprised of eight cases, of which seven were solved by endoscopic endonasal approach and one case was treated through a combined endonasal-external approach. JNA should always be managed through a multidisciplinary team (MDT) approach in centers with adequate experience, to gain favorable results.

Radiofrequency EMF irradiation effects on pre-B lymphocytes undergoing somatic recombination.

Intense electromagnetic fields (EMFs) induce DNA double stranded breaks (DSBs) in exposed lymphocytes.We study developing pre-B lymphocytes following V(D)J recombination at their Immunoglobulin light chain loci (IgL). Recombination physiologically induces DNA DSBs, and we tested if low doses of EMF irradiation affect this developmental stage. Recombining pre-B cells, were exposed for 48 h to low intensity EMFs (maximal radiative power density flux S of 9.5 µW/cm2 and electric field intensity 3 V/m) from waves of frequencies ranging from 720 to 1224 MHz. Irradiated pre-B cells show decreased levels of recombination, reduction which is dependent upon the power dose and most remarkably upon the frequency of the applied EMF. Although 50% recombination reduction cannot be obtained even for an S of 9.5 µW/cm2 in cells irradiated at 720 MHz, such an effect is reached in cells exposed to only 0.45 µW/cm2 power with 950 and 1000 MHz waves. A maximal four-fold recombination reduction was measured in cells exposed to 1000 MHz waves with S from 0.2 to 4.5 µW/cm2 displaying normal levels of γH2AX phosphorylated histone. Our findings show that developing B cells exposure to low intensity EMFs can affect the levels of production and diversity of their antibodies repertoire.

Involvement of inflammatory cells in chronic rhinosinusitis with nasal polyps.

Inflammation plays an important role in the pathogenesis of nasal polyps. Understanding the biomolecular action mechanisms of inflammatory elements can contribute to improving the prognosis of these lesions. The study analyzed the distribution and immunohistochemically quantified eosinophils [eosinophil major basic protein (BMK-13)], lymphocytes [cluster of differentiation (CD) 4, CD8, CD20] and plasmocytes (CD138) in both the epithelial and stromal compartment in relation to composite scores, which included specific histopathological parameters for 50 sinonasal polyps. Inflammatory elements predominated at stromal level, the high histological composite scores being frequently associated with increased expression of inflammatory elements. Also, the numerical distribution of inflammatory elements indicated positive linear relations within the groups BMK-13∕CD8 and CD4∕CD20∕CD138, and a negative linear relation between the two groups. This aspect can support the existence of alternative or sequential pathogenic mechanisms involved in the pathogenesis of sinonasal polyps, and the results obtained can be used for a better stratification of patients in order to optimize the therapy.

Comparative clinicopathological aspects of chronic tonsillitis and adenoiditis in children.

Chronic palatal and nasopharyngeal inflammations are common lesions in pediatric pathology, with major effects on children's development. The study included 34 cases of chronic tonsillitis and adenoiditis for which we quantified immunohistochemically and analyzed the distribution of inflammatory elements in the follicular, extrafollicular and epithelial compartments, in relation to the composite histological scores and the clinico-epidemiological profile of the lesions. The cases were more frequent under the age of 10, in female patients, coming from urban areas, with the diagnosis of tonsillitis. B-lymphocytes have been associated with follicular areas in tonsillitis and epithelial areas in adenoiditis. In all compartments, T-lymphocytes were more frequently associated with tonsillitis and plasma cells associated with adenoiditis. Macrophages and dendritic cells had a relatively uniform distribution for the three compartments in all cases. The results obtained indicate different inflammatory phenotypes for chronic tonsillitis and adenoiditis, an aspect that may be useful for stratifying patients for optimal therapy.

Clinical-morphological profiles of esophageal carcinoma's main types.

AIM: The purpose of the study was to define and then to compare particularly the morphological profiles of the main morphological types of esophageal carcinoma (EC). PATIENTS, MATERIALS AND METHODS: The studied group included 46 operated EC patients. Few parameters were clinical (gender and age). The rest of them described both gross and histological features of the entire group and of the two main histological types of carcinoma (lesion' site, lateral extension, lesion dimensions, gross aspect, and histological type, and tumor grade, and stage). Stratification scales of cases were defined according to each parameter in order to compare the data and a statistical apparatus [Student's t-test and χ² (chi-squared) test] was used. RESULTS: The studied tumors were encountered mostly in mature adult and elderly men, usually in the lower segments of the esophagus. Many of them had between five and ten cm in the long diameter and produced stenosis. Most of them had infiltrating appearance combined often with protruding or∕and ulcerated aspects. Usually, the tumors were poorly differentiated and in stage III. The two main histological types of EC showed different morphological profiles. Data from the literature revealed sometimes wide ranges of variation for the studied morphological parameters. Our results were within these ranges of variation. CONCLUSIONS: ECs proved to be aggressive and late diagnosed tumors in general, with distinct morphological and behavioral profiles for the two main histological types. Comparisons with literature data confirmed many of our observations regarding the clinical and morphological aspects of both ECs as a whole and its histological types.

The Design of New HIV-IN Tethered Bifunctional Inhibitors Using Multiple Microdomain Targeted Docking.

Currently, used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes changes these viral enzymes, which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome of the host T lymphocyte, highlighting its main functional and structural features to be subjected to inhibitory action. From a functional and structural perspective we present all classes of HIV-IN inhibitors with their most representative candidates. For each chosen compound we also explain its mechanism of IN inhibition. We use the recently resolved cryo EM IN tetramer intasome DNA complex onto which we dock various reference IN inhibitory chemical scaffolds such as to target adjacent functional IN domains. Pairing compounds with complementary activity, which dock in the vicinity of a IN structural microdomain, we design bifunctional new drugs which may not only be more resilient to IN mutations but also may be more potent inhibitors than their original counterparts. In the end of our review we propose synthesis pathways to link such paired compounds with enhanced synergistic IN inhibitory effects.

Transglutaminase mediated microencapsulation of sea buckthorn supercritical CO2 extract in whey protein isolate and valorization in highly value added food products.

Sea buckthorn carotenoids extracted using CO2 supercritical fluids method were encapsulated within whey proteins isolate by transglutaminase (TG) mediated crosslinking reaction, coacervation and freeze drying. The encapsulation efficiency was 36.23 ±â€¯1.58%, with ß-carotene the major carotenoid present in the powder. The confocal analysis revealed that TG-ase mediated cross-linking reaction enhanced the complexes stability to such a manner that a double microencapsulation was performed. The powder showed an antioxidant activity of 2.16 ±â€¯0.14 mMol Trolox/g DW and an antifungal activity against Penicillium expansum MIUG M11. Four variants of domestic ice creams were obtained, with a total carotenoids content variation of 1.63 ±â€¯0.03 mg/g D.W. in sample with 2% powder and 6.38 ±â€¯0.04 mg/g D.W. in samples with 4% extract, having satisfactory antioxidant activity. The storage stability test showed a decrease in both total carotenoids content and antioxidant activity in all samples during 21 days at -18 °C. A protective effect of microencapsulation was evidenced.

Chondrosarcoma of the hyoid bone: a case report.

Chondrosarcoma is a malignancy of the mesenchymal tissue derived from transformed cells that produce the cartilage matrix. In the neck area, it represents less than 0.5% of malignant tumor pathology. Chondrosarcoma of the hyoid bone is extremely rare, only 20 cases having been published so far (PubMed 2014). We present the case of a 30-year-old patient from the urban area, admitted in the ENT (Ear, Nose & Throat) Emergency Service with inspiratory dyspnea, dysphagia, stomatolalia, with evolutive and progressive clinical history of 2-3 months. Endoscopic examination revealed a pharyngolaryngeal tumor process located in the right vallecula, who by mass effect displaces the above-hyoid epiglottis. CT (computerized tomography) scan described a cervical polycystic tumor aspect, with multiple septae and inside calcifications with a diameter of 3-4 mm. Surgery consisted in removal of the tumor process together with the hyoid bone. Histopathological and especially immunohistochemical examination established the diagnosis of low-grade chondrosarcoma of the hyoid bone. For assessment of the phenotype of the tumor cells, the following immunohistochemical markers were used: p53, Ki67. The patient followed radiochemotherapic oncological treatment and returned for regular follow-ups. There was a positive development with no signs of regional or remote relapse or metastasis for 24 months after surgical treatment. Surgery is the treatment of choice, with complete removal of the tumor, with chemoradiation playing an adjuvant role. Regular tracking of the patient is mandatory.

TNF-α evaluation in tonsil cancer.

Squamous cell tonsil carcinoma is the most frequent form of oropharyngeal cancer, representing 70-80% of the total of head and neck malignant tumors. Poor clinical symptoms make that 60-80% of patients with squamous cell tonsil carcinoma have a late diagnosis, in the third and fourth stages, when the tumor exceeds the organ limits, invading the pharyngeal wall or the tongue base, being associated with metastases in the laterocervical lymphatic ganglions. The tumor necrosis factor alpha (TNF-α) represents an important inflammation mediator associated to carcinogenesis and even to tumor progression. We evaluated the seric values of TNF-α in a group of patients with tonsil cancer in comparison to a group of patients with chronic tonsillitis, as well as the reaction of mastocytes and macrophages in the two types of tonsil lesions. Seric levels of TNF-α in squamous cell tonsil carcinoma were quite high, varying from 1000 to 2000 pg÷mL, and in four patients, with poorly differentiated tonsil carcinoma in the fourth stage, the TNF-α values varied from 2000 to 4000 pg÷mL. In the patients undergoing radiotherapy, the TNF-α seric levels were within normal limits. In chronic tonsillitis, the TNF-α seric level varied from 10 to 200 pg÷mL. There were not observed any significant differences between the two types of tonsil lesions, regarding the macrophages and mast cells density on the surface unit.

Advances in structure-function relationships of tyrosinase from Agaricus bisporus - investigation on heat-induced conformational changes.

A combination of fluorescence spectroscopic measurements, inactivation kinetics and in silico prediction was used in the present study to investigate the heat induced behaviour of tyrosinase from Agaricus bisporus. The phase diagram indicated the existence of at least two distinct species induced by the temperature increase up to 75°C. Regardless of calcium ion presence, the fluorescence intensity results suggest that tyrosinase tends to form aggregates after 10min at 75°C. The quenching experiments using acrylamide and iodide demonstrate a more flexible conformation of tyrosinase at higher temperature. Detailed insights into tyrosinase structure after performing molecular dynamics simulations, suggest important structural rearrangements of the protein with the temperature increase. The copper coordinating His(94) residue was predicted to be involved in salt bridge formation with Glu(98), therefore causing significant alteration of the substrate binding site with increasing temperature. These significant changes in tyrosinase structure at temperatures over 60°C might lead to enzyme inactivation.

pH-induced structural changes of tyrosinase from Agaricus bisporus using fluorescence and in silico methods.

BACKGROUND: Tyrosinases are involved in enzymatic browning reactions in damaged fruits during post-harvest handling and processing. The overall structure of tyrosinase from Agaricus bisporus mushrooms at different pH values was monitored using fluorescence spectroscopy and molecular dynamics simulations. RESULTS: When the pH value was increased from 6.0 to 9.0, the protein passed through several structural intermediates, including the tetramer, trimer and dimer stages. Changes in the secondary and tertiary structure of tyrosinase at neutral pH were outlined after running molecular dynamics simulations. A detailed check at the single-molecule level by means of molecular modeling tools suggested that the most important contribution to the fluorescence intensity is given by the H subunits with seven Trp and nine Tyr residues exposed to the solvent, whereas the lectin-like folded L subunits have only six Trp and three Tyr residues, of which only Trp(15) , Trp(59) and Trp(93) are partially exposed to the solvent. CONCLUSIONS: The results indicated that the enzyme was sensitive to pH. The experimental results revealed the unfolding of the native tetrameric enzyme in acidic pH range, causing exposure of the hydrophobic residues.

DNA bending in the synaptic complex in V(D)J recombination: turning an ancestral transpososome upside down.

In all jawed vertebrates RAG (recombination activating gene) recombinase orchestrates V(D)J recombination in B and T lymphocyte precursors, assembling the V, D and J germline gene segments into continuous functional entities which encode the variable regions of their immune receptors. V(D)J recombination is the process by which most of the diversity of our specific immune receptors is acquired and is thought to have originated by domestication of a transposon in the genome of a vertebrate.  RAG acts similarly to the cut and paste transposases, by first binding two recombination signal DNA sequences (RSSs), which flank the two coding genes to be adjoined, in a process called synaptic or paired complex (PC) formation. At these RSS-coding borders, RAG first nicks one DNA strand, then creates hairpins, thus cleaving the duplex DNA at both RSSs. Although RAG reaction mechanism resembles that of insect mobile element transposases and RAG itself can inefficiently perform intramolecular and intermolecular integration into the target DNA, inside the nuclei of the developing lymphocytes transposition is extremely rare and is kept under proper surveillance. Our review may help understand how RAG synaptic complex organization prevents deleterious transposition. The phosphoryl transfer reaction mechanism of RNAseH-like fold DDE motif enzymes, including RAG, is discussed accentuating the peculiarities described for various transposases from the light of their available high resolution structures (Tn5, Mu, Mos1 and Hermes). Contrasting the structural 3D organization of DNA in these transpososomes with that of the RSSs-DNA in RAG PC allows us to propose several clues for how evolutionarily RAG may have become "specialized" in recombination versus transposition.

Morphology and morphopathology of hypopharyngo-esophageal cancer.

Cervical esophageal cancer and hypopharyngeal cancer represent a major diagnostic issue in early stages, considering the fact that the implication of both cervical esophageal and hypopharyngeal cancers shows a poor prognostic from the very beginning. Positive diagnosis can only be made after histopathological analysis and immunohistochemical analysis in addition. The bioptic material is sampled by rigid endoscopy this being the only viable method of assessing data on the tumor prior to the surgery. As much as 95% of tumors located at this site are epidermoid carcinomas with different staging and characteristics, other types of tumors being adenocarcinomas, lymphomas, etc. Several risk factors influence the biology of this site thus inflicting both cellular and molecular modifications that are the origin of cancer development.

Histopathological and immunohistochemical study of laterocervical lymph node metastases of unknown primary origin.

In this study, we examined histopathologically and immunohistochemically 24 cases of laterocervical lymph node metastases with unknown primary origin. For immunohistochemical study, we used a large panel of antibodies represented by CK7, CK19, CK20, CKAE1/AE3, CK34betaE12, TTF1, HBME-1, CEA, MUC5AC and EBV. In the cases studied tumors accompanied by seemingly primitive adenopathies were located in the thyroid, lung, esophagus, stomach, rhinopharynx, hypopharynx, oropharynx and larynx.

Non-Hodgkin lymphomas of Waldeyer's ring.

Lymphomas represent malignant lymphoproliferative diseases and they are generally classified as Hodgkin's (HL) or non-Hodgkin malignant lymphomas (NHML). Head and neck lymphomas represent one of the most common sites of extranodal lymphomas, second after the gastrointestinal tract. Waldeyer's ring structures include the palatine tonsils, the nasopharyngeal lymphatic tissue, and the lingual tonsil. We investigated 38 patients with malignant lymphoma with ages ranging from 21 to 95 years, all localized in the Waldeyer's ring. Good knowledge of the clinical characteristics of these lymphomas and the methods to establish the differential diagnosis are essential for a correct therapy of the disease.

Histopathological and immunohistochemical aspects in chronic suppurative maxillary rhinosinusitis.

Chronic rhinosinusitis is a multifactorial disease with pathophysiological mechanisms, which remain unclear, and with a high prevalence worldwide. They generate social problems due to the high number of days of leave and relatively elevated medical expenses. The histopathological and immunohistochemical study that we conducted revealed many lesional aspects of the epithelium of the sinus mucosa, which ranged from hypertrophy, hyperplasia and metaplasia, to erosion and discontinuities. In the chorion of the sinus mucosa there was an inflammatory infiltrate composed mainly of lymphocytes, plasma cells and macrophages, and also a highly developed vascular network. Among immune cells, T-cells appeared to be more numerous than B-lymphocytes and macrophages. We believe that microscopic changes are due mainly to microscopic organisms that make up the biofilm of the sinus cavity, whose virulence has been more or less influenced by exogenous or endogenous factors.

The importance of tumor proliferation markers in assessing lesions of the palatine tonsil.

Oropharyngeal cancer, and especially squamous cell carcinoma, is one of the most common cancers worldwide, and its incidence is increasing, with the palatine tonsil being one of the main locations. The etiopathogenic factors, together with its location as well as the available immunohistochemical methods, make this type of cancer an accessible one in terms of diagnosis. However, it is usually diagnosed in late stages. Therefore, we tried to elucidate the causes of treatment failures and development of local recurrence. For this, we reassessed the proliferative pattern of tonsil lesions using the anti-p53, anti-PCNA and anti-Ki67 antibodies on 73 tonsil fragments collected after curative surgery on adults aged between 28 and 86 years. Following the reevaluation of the histopathological examination using markers for cell proliferation, the diagnosis was modified in 16 cases, representing about 22% of the cases take into study. By using immunohistochemical markers in the histopathological examination the diagnosis is improved, leading to a more appropriate therapeutical approach.