Postmenopausal onset of androgen excess: a diagnostic and therapeutic algorithm based on extensive clinical experience.

PURPOSE: Postmenopausal hyperandrogenism is a rare condition that requires identifying those women bearing a life-threatening tumor. We aimed to study diagnostic work-up and management of postmenopausal androgen excess, proposing an algorithm for clinical decision supporting. METHODS: We conducted an observational cross-sectional study and longitudinal follow-up including 51 consecutive menopausal patients reported for hyperandrogenism between 2003 and 2023 to our clinics. We assessed diagnostic testing accuracy and performance by receiver operating characteristic curves, their respective areas under the curve (AUCROC), and 95% confidence intervals (95%CI), for distinguishing between benign and malignant conditions, and androgen excess source. RESULTS: Most commonly, postmenopausal hyperandrogenism derived from benign conditions such as ovarian hyperthecosis (n = 9). However, four (8%) patients had borderline/malignant tumors arising at the ovaries (n = 3) or adrenals (n = 1). These latter were more likely to develop virilization than those with benign disorders [specificity(95%CI)]: 0.87 (0.69; 0.92)]. Circulating total testosterone [AUCROC(95%CI): 0.899 (0.795; 1.000)] and estradiol [AUCROC(95%CI): 0.912 (0.812; 1.000)] concentrations showed good performances for discriminating between both conditions. Transvaginal-ultrasonography found two out of three potentially malignant ovarian neoplasms, and another was apparent on a pelvic computed tomography scan. An adrenal computed tomography scan also located an androgen-secreting carcinoma. CONCLUSIONS: Clinical or biochemical features of an aggressive androgen-secreting tumor should lead to urgently obtaining a targeted imaging. At first, an abdominal-pelvic CT scan represents the best choice to perceive adrenal malignancy, and may identify aggressive ovarian tumors. When warning signs are lacking, a calm and orderly work-up allows properly addressing the diagnostic challenge of postmenopausal hyperandrogenism.

Satisfaction analysis of overground gait exoskeletons in people with neurological pathology. a systematic review.

BACKGROUND: People diagnosed with neurological pathology may experience gait disorders that affect their quality of life. In recent years, research has been carried out on a variety of exoskeletons in this population. However, the satisfaction perceived by the users of these devices is not known. Therefore, the objective of the present study is to evaluate the satisfaction perceived by users with neurological pathology (patients and professionals) after the use of overground exoskeletons. METHODS: A systematic search of five electronic databases was conducted. In order to be included in this review for further analysis, the studies had to meet the following criteria: [1] the study population was people diagnosed with neurological pathology; [2] the exoskeletons had to be overground and attachable to the lower limbs; and [3]: the studies were to include measures assessing either patient or therapist satisfaction with the exoskeletons. RESULTS: Twenty-three articles were selected, of which nineteen were considered clinical trials. Participants diagnosed with stroke (n = 165), spinal cord injury (SCI) (n = 102) and multiple sclerosis (MS) (n = 68). Fourteen different overground exoskeleton models were analysed. Fourteen different methods of assessing patient satisfaction with the devices were found, and three ways to evaluate it in therapists. CONCLUSION: Users' satisfaction with gait overground exoskeletons in stroke, SCI and MS seems to show positive results in safety, efficacy and comfort of the devices. However, the worst rated aspects and therefore those that should be optimized from the users' point of view are ease of adjustment, size and weight, and ease of use.

Modern Concepts in Melanocytic Tumors. / Conceptos modernos en tumores melanocíticos.

The advent of molecular pathology has fueled unprecedented advances in the diagnosis and understanding of melanocytic tumors. These advances, however, have also generated concepts that may be difficult to grasp for clinical practitioners, who are not always conversant with the array of genetic techniques employed in the laboratory. These same practitioners, however, are being increasingly called on to provide treatments that are often based on the latest molecular findings for melanocytic tumors. We review the most recent concepts in the pathway classification of melanocytic tumors, including intermediate lesions known as melanocytomas. We examine the genetic and molecular techniques used to study these tumors, look at where they overlap, and discuss their limitations and some of the most difficult-to-interpret results.

[Translated article] Histopathologic and Trichoscopic Correlations in Nonscarring Alopecias.

Trichoscopy is an essential tool in the evaluation of alopecia. The current compilation of trichoscopic signs in this setting helps distinguish between different forms of hair loss and has improved our understanding of the pathogenic mechanisms involved. The trichoscopic signs are always linked to the pathogenic mechanisms of the alopecia being examined. We examine correlations between the main trichoscopic and histopathologic findings in nonscarring alopecias.

Vascular Malformations: A Histopathologic and Conceptual Appraisal.

In the field of vascular anomalies, distinguishing between vascular malformations and tumors has become crucial for a correct therapeutic approach. However, the differential diagnosis between these two groups is not always well explained in classical texts, mainly because many vascular malformations are still known with old names that suggest a tumoral nature. Also, genetic and pathogenic knowledge of these entities has greatly increased in recent decades, so researchers and clinicians now have a better understanding of vascular malformations. In this paper, we present the main histopathological tips to recognize and identify a vascular malformation as such. We also contextualize such information in the clinical and pathogenic knowledge for a better understanding of these entities.

Vascular Malformations: A Histopathologic and Conceptual Appraisal. / [Artículo traducido] Malformaciones vasculares: un enfoque histopatológico y conceptual.

In the field of vascular anomalies, distinguishing between vascular malformations and tumors has become crucial for a correct therapeutic approach. However, the differential diagnosis between these two groups is not always well explained in classical texts, mainly because many vascular malformations are still known with old names that suggest a tumoral nature. Also, genetic and pathogenic knowledge of these entities has greatly increased in recent decades, so researchers and clinicians now have a better understanding of vascular malformations. In this paper, we present the main histopathological tips to recognize and identify a vascular malformation as such. We also contextualize such information in the clinical and pathogenic knowledge for a better understanding of these entities.

Effects of ATLAS 2030 gait exoskeleton on strength and range of motion in children with spinal muscular atrophy II: a case series.

BACKGROUND: Children with spinal muscular atrophy (SMA) present muscle weakness and atrophy that results in a number of complications affecting their mobility, hindering their independence and the development of activities of daily living. Walking has well-recognized physiological and functional benefits. The ATLAS 2030 exoskeleton is a paediatric device that allows gait rehabilitation in children with either neurological or neuromuscular pathologies with gait disorders. The purpose is to assess the effects in range of motion (ROM) and maximal isometric strength in hips, knees and ankles of children with SMA type II after the use of ATLAS 2030 exoskeleton. METHODS: Three children (mean age 5.7 ± 0.6) received nine sessions bi-weekly of 60 min with ATLAS 2030. ROM was assessed by goniometry and strength by hand-held dynamometer. All modes of use of the exoskeleton were tested: stand up and sit down, forward and backward walking, and gait in automatic and active-assisted modes. In addition, different activities were performed during the gait session. A descriptive analysis of all variables was carried out. RESULTS: The average time of use was 53.5 ± 12.0 min in all sessions, and all participants were able to carry out all the proposed activities as well as to complete the study. Regarding isometric strength, all the measurements increased compared to the initial state, obtaining the greatest improvements for the hip flexors (60.2%) and extensors muscles (48.0%). The ROM increased 12.6% in hip and 34.1% in the ankle after the study, while knee ROM remained stable after the study. CONCLUSION: Improvements were showed in ROM and maximal isometric strength in hips, knees and ankles after using ATLAS 2030 paediatric gait exoskeleton in all three children. This research could serve as a preliminary support for future clinical integration of ATLAS 2030 as a part of a long-term rehabilitation of children with SMA. TRIAL REGISTRATION: The approval was obtained (reference 47/370329.9/19) by Comunidad de Madrid Regional Research Ethics Committee with Medical Products and the clinical trial has been registered on Clinical Trials.gov: NCT04837157.

Effects of mesenchymal stem cell culture on radio sterilized human amnion or radio sterilized pig skin in burn wound healing.

Deep second and third degree burns treatment requires fibroblasts, keratinocytes and other skin cells in order to grow new dermis and epidermis. Cells can proliferate, secrete growth factors and extracellular matrix required to repair the damaged tissue. Radiosterilized human amnion and radiosterilized pig skin have been used as natural origin skin dressings for burned patients. Adipose-derived mesenchymal stem cells can differentiate into fibroblasts and keratinocytes and improve wound-healing progress. These cells can stimulate vascular tissue formation, release growth factors, synthetize new extracellular matrix and immunoregulate other cells. In this study, we developed mesenchymal stem cells-cellularized skin substitutes based from radiosterilized human amnion or pig skin. Third-degree burns were induced in mice animal models to evaluate the effect of cellularized skin substitutes on burn wound healing. Mesenchymal phenotype was immunophenotypically confirmed by flow cytometry and cell viability was close to 100%. Skin recovery was evaluated in burned mice after seven and fourteen days post-coverage with cellularized and non-cellularized sustitutes. Histological techniques and immunofluorescence were used to evaluate re-epithelization and type I collagen deposition. We determined that cellularized-human amnion or cellularized-pig skin in combination with mesenchymal stem cells improve extracellular matrix deposition. Both cellularized constructs increase detection of type I collagen in newly formed mouse skin and can be potentially used as skin coverage for further clinical treatment of burned patients.

The identification of byproducts from the catalytic reduction reaction of 4-nitrophenol to 4-aminophenol: A systematic spectroscopic study.

Acetaminophenol, commonly recognized as paracetamol (considered safer than aspirin) is formed by nitration of phenol (4-nitrophenol (4-NP)) for its conversion to 4-aminophenol (4-AP), followed by the acetylation for the final product. As 4-NP is an intermediate product in acetaminophenol (paracetamol) production from phenol the dynamic analysis of acetylation of amine group is important. This study focuses on the feasibility of spectroscopic studies to monitor the removal of 4-NP using sodium borohydride (NaBH4) probe reaction in the presence of silver, gold, and bimetallic Ag/Au nanoparticles. UV-visible absorbance and fluorescence spectroscopy measurements reveal the formation of 1,4-benzoquinone (BQ), hydroquinone (HQ), and phenol (Ph) as the final products, in addition to the formation of typically reported 4-AP. The intermediates of NaBH4 seem to play a significant role in the formation of BQ, which converts to HQ in the basic medium followed by the formation of phenol in an acidic medium. Complete kinetic analysis with respect to spectroscopic studies of the standard compounds is presented. Similar results were obtained with 4-NP spiked river and seawater samples. The present findings may lead to catalytic benchmarking that can differ from most of the current practices and highlight the importance of adopting a holistic approach towards the fundamental understanding of 4-NP catalytic reduction that must take into account the concentration of NaBH4 and pH interdependencies.

Effect of the charge state on the structure of the Au60 cluster.

This manuscript outlines a DFT-D study of a neutral and charged Au60 cluster. The neutral structure features an I-symmetry, while 1-, 1+, and 2+ charge states result in a structure with Cs symmetry. The main difference among neutral and charged clusters is their compactness and we used a polyhedral approach to analyze their structure in terms of tetrahedral and octahedral building blocks. Moreover, we calculated their IR/Raman spectra to distinguish among them.

On the structure of Au11(SR)9 and Au13(SR)11 clusters.

Thiolated gold clusters are constituted by building blocks (Au4, Au6, Au12 and so on) and protected by staple motifs (-S-Au-S-Au-S-…). In this study, we propose the structure of Au11(SR)9 and Au13(SR)11 clusters that are in the synthesis route of the ubiquitous Au15(SR)13 cluster. Our DFT-D calculations support one triangular Au3 unit as the smallest one comprising the structure of the Au11(SR)9 cluster, while it competes with the Au4 unit found in the Au13(SR)11 cluster. The ligand effects on the electronic, optical and chiroptical properties were studied by considering H, CH3, phenyl and adamantyl as protecting ligands. In the case of the Au11(SR)9 cluster, its Au3 inner core is protected by one dimer motif and one [Au6(SR)6] cyclomer when H and CH3 were considered as ligands, and the preference for Au3 over Au4 inner core was calculated to be 0.042 (H), 0.190 (CH3), and 0.117 eV (adamantyl). In contrast, the preference for one Au4 core increased when using phenyl ligands (0.23 eV energy difference) and dimer and pentamer motifs. Moreover, the Au13(SR)11 cluster (R = CH3) has one Au4 inner core and is protected by the combination of cyclomer, monomer and dimer motifs, and the isomer containing one Au3 inner core and protected by one tetramer and one [Au6(SR)6] cyclomer is 0.170 eV less stable. This implies that the Au3 unit is important in these small sizes and that the energetic preference depends on the used ligand types. Moreover, we discuss the IR/Raman, optical absorption (UV-vis), and circular dichroism (CD) spectra of our predicted new structures.

Outcomes of patients on second- and third-line ART enrolled in ART adherence clubs in Maputo, Mozambique.

OBJECTIVES: Adherence clubs (AC) offer patient-centred access to antiretroviral therapy (ART) while reducing the burden on health facilities. AC were implemented in a health centre in Mozambique specialising in patients with a history of HIV treatment failure. We explored the impact of AC on retention in care and VL suppression of these patients. METHODS: We performed a retrospective analysis of patients enrolled in AC receiving second- or third-line ART. The Kaplan-Meier estimates were used to analyse retention in care in health facility, retention in AC and viral load (VL) suppression (VL < 1000 copies/mL). Predictors of attrition and VL rebound (VL ≥ 1000 copies/mL) were assessed using multivariable proportional hazards regression. RESULTS: The analysed cohort contained 699 patients, median age 40 years [IQR: 35-47], 428 (61%) female and 97% second-line ART. Overall, 9 (1.3%) patients died, and 10 (1.4%) were lost to follow-up. Retention in care at months 12 and 24 was 98.9% (95% CI: 98.2-99.7) and 96.4% (95% CI: 94.6-98.2), respectively. Concurrently, 85.8% (95% CI: 83.1-88.2) and 80.9% (95% CI: 77.8-84.1) of patients maintained VL suppression. No association between predictors and all-cause attrition or VL rebound was detected. Among 90 patients attending AC and simultaneously having VL rebound, 64 (71.1%) achieved VL resuppression, 10 (11.1%) did not resuppress, and 14 (15.6%) had no subsequent VL result. CONCLUSION: Implementation of AC in Mozambique was successful and demonstrated that patients with a history of HIV treatment failure can be successfully retained in care and have high VL suppression rate when enrolled in AC. Expansion of the AC model in Mozambique could improve overall retention in care and VL suppression while reducing workload in health facilities.

OBJECTIFS: Les clubs d'adhésion (CA) offrent un accès centré sur le patient à la thérapie antirétrovirale (ART) tout en réduisant la charge des établissements de santé. Les CA ont été mis en œuvre dans un centre de santé au Mozambique spécialisé dans les patients ayant des antécédents d'échec du traitement du VIH. Nous avons exploré l'impact des CA sur la rétention dans les soins et la suppression de la CV chez ces patients. MÉTHODES: Nous avons effectué une analyse rétrospective des patients enrôlés dans les CA sous ART de deuxième ou troisième intention. Les estimations de Kaplan-Meyer ont été utilisées pour analyser la rétention dans les soins dans les établissements de santé, la rétention dans les CA et la suppression de la charge virale (CV) (CV <1000 copies/mL). Les prédicteurs de l'attrition et du rebond de la CV (VL ≥ 1000 copies/mL) ont été évalués à l'aide d'une régression à risques proportionnels multivariés. RÉSULTATS: La cohorte analysée contenait 699 patients, d'âge médian 40 ans [IQR: 35-47], 428 (61%) femmes, 97% de traitement de deuxième intention. Dans l'ensemble, 9 (1,3%) patients sont décédés, 10 (1,4%) ont été perdus de vue. La rétention dans les soins à 12 et 24 mois était de 98,9% (IC95%: 98,2-99,7) et de 96,4% (IC95%: 94,6-98,2), respectivement. De même, 85,8% (IC95%: 83,1-88,2) et 80,9% (IC95%: 77,8-84,1) des patients ont maintenu une suppression de la CV. Aucune association entre les prédicteurs et l'attrition toutes causes ou le rebond de la CV n'a été détectée. Parmi 90 patients enrôlés dans les CA et ayant simultanément un rebond de la CV, 64 (71,1%) ont atteint une re-suppression de la CV, 10 (11,1%) n'ont pas atteint une re-suppression et 14 (15,6%) n'avaient pas de résultats de CV ultérieurs. CONCLUSION: La mise en œuvre des CA au Mozambique a été un succès et a démontré que les patients ayant des antécédents d'échec du traitement anti-VIH peuvent être retenus avec succès dans les soins et ont un taux élevé de suppression de la CV lorsqu'ils sont enrôlés dans les CA. L'expansion du modèle CA au Mozambique pourrait améliorer la rétention globale dans les soins et la suppression de la CV tout en réduisant la charge de travail dans les établissements de santé.

Augmenting Global Coherence in EEG Signals with Binaural or Monaural Noises.

Internal stochastic resonance (internal SR) is a phenomenon of non-linear systems in which the addition of a non-zero level of noise produces an enhancement in the coherence between two or more signals. In a previous study, we found that the simultaneous administration of multisensory visual and auditory noise augments global coherence in electroencephalographic (EEG) signals via this phenomenon. Here, we examined whether such global coherence can also be augmented with at least one noisy acoustic source. We performed experiments on healthy subjects and applied the following binaural and monaural noise-stimulation protocols. First, we administered to the left ear Gaussian noise of fixed intensity, while we delivered to the right ear a second Gaussian noise of variable intensity levels (binaural protocol). Second, we applied the Gaussian noise of the same variable intensity levels but only to one ear (monaural protocol). We performed a permutation test analysis, finding that during both noise protocols there was a significant enhancement in the global coherence in EEG signals via the occurrence of internal SR within central pathways of the auditory system.

A new lower limb portable exoskeleton for gait assistance in neurological patients: a proof of concept study.

BACKGROUND: Few portable exoskeletons following the assist-as-needed concept have been developed for patients with neurological disorders. Thus, the main objectives of this proof-of-concept study were 1) to explore the safety and feasibility of an exoskeleton for gait rehabilitation in stroke and multiple sclerosis patients, 2) to test different algorithms for gait assistance and measure the resulting gait changes and 3) to evaluate the user's perception of the device. METHODS: A cross-sectional study was conducted. Five patients were recruited (4 patients with stroke and 1 with multiple sclerosis). A robotic, one-degree-of-freedom, portable lower limb exoskeleton known as the Marsi Active Knee (MAK) was designed. Three control modes (the Zero Force Control mode, Mode 1 and Mode 3) were implemented. Spatiotemporal gait parameters were measured by the 10-m walking test (10MWT), the Gait Assessment and Intervention Tool (G.A.I.T.) and Tinetti Performance Oriented Mobility Assessment (gait subscale) before and after the trials. A modified QUEST 2.0 questionnaire was administered to determine each participant's opinion about the exoskeleton. The data acquired by the MAK sensors were normalized to a gait cycle, and adverse effects were recorded. RESULTS: The MAK exoskeleton was used successfully without any adverse effects. Better outcomes were obtained in the 10MWT and G.A.I.T. when Mode 3 was applied compared with not wearing the device at all. In 2 participants, Mode 3 worsened the results. Additionally, Mode 3 seemed to improve the 10MWT and G.A.I.T. outcomes to a greater extent than Mode 1. The overall score for the user perception of the device was 2.8 ± 0.4 95% CI. CONCLUSIONS: The MAK exoskeleton seems to afford positive preliminary results regarding safety, feasibility, and user acceptance. The efficacy of the MAK should be studied in future studies, and more advanced improvements in safety must be implemented.

Crenosoma Striatum in Lungs of European Hedgehogs (Erinaceus Europeus) from Portugal.

Crenosoma striatum is a host-specifi c metastrongiloid nematode causing respiratory tract disease in hedgehogs (Erinaceus europaeus). Since few studies have reported C. striatum in hedgehogs and little genetic data is available concerning this lungworm, this study aimed to determine the occurrence of C. striatum in a population sample of hedgehogs from Portugal, additionally providing morphological, histological and molecular data. From 2017 to 2018 a survey of infection was carried out in 11 necropsied hedgehogs. Worms were extracted from fresh lung tissues and microscopically evaluated. Molecular characterization of partial mitochondrial (12S rRNA) and nuclear (18S rRNA) genes was performed. The presence of lungworms in pulmonary tissues of five hedgehogs (45.5%) was detected. Morphological and histopathological analyses evidenced adult forms of nematodes consistent with C. striatum. Molecular characterization of 18S rRNA genes confirmed the classifi cation as C. striatum. Also, novel genetic data characterizing the mitochondrial (12S rRNA) gene of C. striatum is presented. This is the first report of C. striatum infection in hedgehogs of Portugal. The findings here reported provide new insights regarding the geographic distribution and the molecular identification of this lungworm species.

Effect of the charge state on bare monoicosahedral [Au13]z+ and diphosphine-protected Au13 clusters [Au13(dmpe)5Cl2]z+: structural, electronic and vibrational DFT studies.

In this paper a GGA-PBE study of [Au13]z+ bare clusters (z = +3, +5) and diphosphine protected [Au13(dmpe)5Cl2]z+ clusters (z = 1, 3) is presented. To explore the application of the [Au13((P(CH3)2CH2)2)5Cl2]3+ cluster as a cisplatin carrier, we have evaluated the adsorption energy of one cisplatin dimer interacting with the complex (0.53 eV). By considering a 1+ charge state, we have determined one cluster featuring a slight reduced HOMO-LUMO gap, with an inner Au13 core heavily distorted (strong charge effects). It is found that the filling/distribution of the superatomic energy levels is affected by the addition of two electrons to the [Au13(dmpe)5Cl2]3+ cluster with a reduction of its symmetry (C1 point group). In addition, the calculated IR and Raman spectra of charged [Au13(dmpe)5Cl2]z+ clusters allow distinguishing them.

New two-dimensional carbon nitride allotrope with 1 : 1 stoichiometry featuring spine-like structures: a structural and electronic DFT-D study.

In this communication the prediction of a two-dimensional carbon nitride allotrope (CN) featuring a 1 : 1 stoichiometry is considered. Calculations were carried out under ambient conditions of pressure and temperature (1 atm, 300 K), to prove its dynamic (phonon) and thermal stability. The novel CN structure contains pentagonal rings (c-C3N2) linked by nitrogen atoms, and separated by holes, whereas the sp3-like C atoms are bonded to isocyano (C[triple bond, length as m-dash]N-) groups projecting out of its surface and resembling spine-like formations. The predicted structure has a calculated indirect bandgap of approximately 2.78 eV (hybrid HSE06 approximation), that is in the range of visible light, and this it might increase its use in the field of photocatalysis.

Raman Spectroscopy and Chemometric Modeling to Predict Physical-Chemical Honey Properties from Campeche, Mexico.

In this work, 10 chemometric models based on Raman spectroscopy were constructed to predict the physicochemical properties of honey produced in the state of Campeche, Mexico. The properties of honey studied were pH, moisture, total soluble solids (TSS), free acidity, lactonic acidity, total acidity, electrical conductivity, Redox potential, hydroxymethylfurfural (HMF), and ash content. These proprieties were obtained according to the methods described by the Association of Official Analytical Chemists, Codex Alimentarius, and the International Honey Commission. For the construction of the chemometric models, 189 honey samples were collected and analyzed in triplicate using Raman spectroscopy to generate the matrix data [X], which were correlated with each of the physicochemical properties [Y]. The predictive capacity of each model was determined by cross validation and external validation, using the statistical parameters: standard error of calibration (SEC), standard error of prediction (SEP), coefficient of determination of cross-validation (R2cal), coefficient of determination for external validation (R2val), and Student's t-test. The statistical results indicated that the chemometric models satisfactorily predict the humidity, TSS, free acidity, lactonic acidity, total acidity, and Redox potential. However, the models for electric conductivity and pH presented an acceptable prediction capacity but not adequate to supply the conventional processes, while the models for predicting ash content and HMF were not satisfactory. The developed models represent a low-cost tool to analyze the quality of honey, and contribute significantly to increasing the honey distribution and subsequently the economy of the region.

Non-muscle myosin II as a predictive factor in head and neck squamous cell carcinoma.

BACKGROUND: The present study attempted to provide information regarding non-muscle myosin II (MII) isoforms immunoreactivity in patients with head and neck squamous cell carcinoma (HNSCC) and analysis of the patients' clinical status after 5 years of monitoring. MATERIAL AND METHODS: A semiquantitative analysis of the immunoreactivity of the MII isoforms was performed in 54 surgical specimens and its correlation with clinical and pathological variables and prognosis was verified. Data were analyzed using chi-square, Mann-Whitney and Kruskal-Wallis tests. To evaluate the survival over the total monitoring time and any connection with the proteins studied, the Kaplan-Meier analysis was used. P values ≤0.05 were considered statistically significant. RESULTS: In the advanced stages of pathological tumor-node-metastasis, the expression of MIIB in adjacent non-neoplastic epithelial tissues tended to increase (p = 0.057). In tumoral zones there was an association of high expression among the three isoforms (MIIA/MIIB p=0,001, MIIB/MIIC p=0,006 and MIIA/MIIC p=0,012). Negative clinical evolution in patients was directly correlated to increased MIIC expression in the tumoral zone of invasion in HNSCC (p = 0.017). Based on clinical evolution after the monitoring period, patients with tumors expressing MIIC had poorer prognoses (p = 0.048). CONCLUSIONS: The present study suggests that MIIB expression in non-neoplastic adjacent epithelial tissues may indicate a potential for regional metastasis and that MIIC expression in the tumoral zone of invasion is predictive of negative evolution of the disease.