Basal Zone Research Articles

Mucous membrane pemphigoid - a report of four cases

Introduction. Mucous membrane pemphigoid (MMP) is a rare autoimmune, chronic inflammatory disease that affects mucous membranes, most commonly the eyes and mouth, with or without skin involvement. It is a complex disease with several complications, including scarring, especially on conjunctival mucosa, that can lead to visual loss. Case report. We report four patients (two men and two women) with MMP. In all patients, the disease started between seventy and eighty years of age. The diagnosis was confirmed based on clinical appearance, histology, direct and indirect immunofluorescence studies, indirect split skin technique, and enzyme-linked immunosorbent assay (ELISA) test. The majority of lesions were on the gums and buccal mucosa; one patient had laryngeal involvement and a lesion on the umbilicus. No ocular involvement and no malignancy were detected. Direct immunofluorescence tests revealed continuous linear IgG deposition in the basal membrane zone in two patients, and they were treated with oral nicotinamide and tetracycline hydrochloride. In two patients, we detected IgG along with IgA linear deposition; they received treatment with methylprednisolone. Complete remission was achieved in all patients. Conclusion. Early diagnosis and an adequate therapeutic approach are necessary for the MMP treatment in long-term disease control and reduction of disease-related complications.

Bullous scabies, the light shed on etiopathogenesis and treatment: report of five paediatric cases.

Bullous scabies (BS) is an infrequent and atypical presentation of scabies, with a predilection for elderly males. The mechanism of BS is not fully understood; superinfection, friction due to pruritus, autoeczemation, direct injury from mite's lytic enzymes, cross-reactivity of scabies protein with basal membrane zone antigens are considered to be possible reasons. To define clinical features of paediatric BS cases, which is an extremely rare subtype of scabies. This is a retrospective study of paediatric BS cases seen at two tertiary care centres. Previously described bacterial culture, antibiogram and follow-up records were investigated retrospectively. Confirmed scabies cases, according to the "International Alliance for the Control of Scabies (IACS)" with bullae were included. All cases were treated with 10% sulfur ointment for 3 consecutive days, two cycles. Households of cases were also treated simultaneously. Systemic antibiotics were added to patients with elevated acute phase reactants according to the antibiogram results. Informed consent was obtained from patients' parents. Five BS cases were included. Three cases were male, two cases were female. Four cases had staphylococcus aureus, one had group-A beta haemolytic streptococcus positive bullae culture. All cases achieved a rapid complete resolution of symptoms after topical 10% sulfur ointment. Paediatric BS is an extremely rare entity of scabies. Bacterial superinfection plays a key role in bullae formation. 10% sulfur ointment is a highly effective treatment option for paediatric BS.

Клинико-морфологическая диагностика эозинофильного эзофагита

Eosinophilic esophagitis (EoE) is an immune-mediated disease that presents with dysphagia and esophageal bolus obstruction and is characterized by predominant intraepithelial eosinophilic infiltration at histology. The aim of our literature review was to delineate clinical and morphological EoE features in terms of differential diagnosis with other esophageal diseases, i.e., gastroesophageal reflux disease (GERD), inflammatory bowel diseases (IBDs), autoimmune diseases, and rare esophageal disorders. Clinical features of dysphagia and esophageal bolus obstruction and endoscopic criteria (according to EREFS) are typical of EoE. Nevertheless, eosinophilia of the esophageal mucosa is not a specific marker of mucosal injury and is not sufficient for EoE diagnosis. Therefore, eosinophilic esophagitis histological scoring system (EoEHSS) was developed. It involves assessment of intraepithelial eosinophilic infiltration, basal zone hyperplasia, eosinophilic abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Complex clinical, endoscopic, and histological evaluation allows accurate diagnosis of EoE and other causal factors of esophageal eosinophilia. Keywords: eosinophilic esophagitis, esophageal eosinophilia, gastroesophageal reflux disease, celiac disease, inflammatory bowel diseases, achalasia, atopy

Eozinofilni ezofagitis

Eosinophilic esophagitis (EoE) is an inflammatory disorder characterized by intraepithelial eosinophilic infiltration followed by esophageal dysfunction. Pathophysiological mechanism of EoE is still not well understood, with several factors that may contribute, such as host immunity, environmental and genetic factors. Modern diagnostic for EoE should include: esophageal dysfunction, esophageal biopsy with at least 15 eosinophils per high power field and absence of other pathology characterized by increased number of eosinophils. The most common presenting symptoms in adults are dysphagia, heartburn, food impaction and chest pain. Children are usually presented with nausea and vomiting, anorexia, heartburn, regurgitation, chest burn and abdominal pain. Endoscopically, patients with EoE are characterized by longitudinal furrows (vertical lines, darker than surrounding mucosa), esophageal trachealization (numerous transversal rings, as in trachea), exudate (white plaques), edema (decreased mucosal vascularization), strictures and crepe-paper mucosa (mucosal friability and tearing during endoscopy). Histological features of EoE could be separated into major and minor criteria. Major criteria include: intraepithelial infiltration by eosinophils (>15 eosinophils/HPF), eosinophilic microabscesses (≥4 eosinophils in a collection), eosinophils occupying outer layer of the squamous epithelium, epithelial sloughing and eosinophil degranulation. Minor criteria include: basal zone hyperplasia, lengthening of the epithelial papillae, intracellular edema and subepithelial fibrosis. In order to set adequate diagnosis, all other conditions related to increased number of eosinophils should be excluded. The most common and the most important differential is gastroesophageal reflux disease (GERD). Treatment of the EoE encompasses: proton pump inhibitors (PPI), corticosteroids (topical and systemic), elimination diet and esophageal dilation.

Characterization of blocks within a near seafloor Neogene MTC, Orange Basin: Constraints from a high-resolution 3D seismic data

Submarine mass wasting processes in deepwater settings can incorporate large blocks, which may play a key role in deepwater geological processes and geohazard assessment. However, there is a limited understanding of the deformation style arising from the interaction between submarine blocks and structural/bathymetric barriers such as ramps. The deformation and kinematic history of several submarine blocks (with a thickness of up to 150 m) within a near seafloor mass transport complex in the Orange Basin are documented using seismic geomorphic methods. The interpreted blocks are preserved in three discrete fault-bounded morphological terrains within a Neogene mass-transport complex. These terrains vary in lengths from 2 km to 6 km; they have heights of 60 m to 150 m and are characterized by discrete and localized structural highs on the present-day seafloor. Block sizes vary across terrains suggesting differences in the block evolution process. Blocks near the ramp appear in seismic profiles comprising (a) Chaotic and transparent seismic reflections and (b) parallel to sub-parallel, continuous, low to moderate amplitude reflections. This variability in seismic facies of the blocks reflects the degree of their interaction and translation over a ramp at the basal shear zone of the mass transport complex, evidenced by the difference in the block features on the upslope portion of the ramp versus the downslope part. Notably, the deformation styles recorded in the blocks show the impact of the ramp during mass flow, which has broader implications for understanding the internal mechanisms of blocky mass transport complexes in many continental margins.

Emplacement dynamics of a crystal-rich, highly viscous trachytic flow of the Sancy stratovolcano, France

Emplacement dynamics of highly viscous, silicic lava flows remain poorly constrained due to a lack of consideration of crystal-rich cases. Emplacement models mostly apply to glassy or microlitic, vesiculated rhyolitic flows. However, crystalline, vesicle-free silicic lava can flow differently. We studied the Grande Cascade unit, which is a vesicle-free, phenocryst-rich, trachytic flow in the Monts Dore massif, France. Field work was carried out to define internal structures, and oriented samples were collected for chemical, petrological, and anisotropy of magnetic susceptibility analyses, allowing us to estimate emplacement temperature and viscosity. These data allow us to define a new silicic lava flow subtype that is low in temperature (800−900 °C), high in silica content (up to 66.8 wt%), high in viscosity (109−1011 Pa s), rich in phenocrysts (∼35%), and lacks vesicles. Brittle deformation of the lava occurs upon extrusion, generating a cataclasite basal layer and thin (3-m-thick) shear zone that accommodates all of the stress, allowing most of the flow’s volume to slide over its base as a 40-m-thick plug in which there is no deformation. Blocks are rare, of a single size (10 ± 1 cm), and result from localized break-up of the basal shear zone. Emplacement dynamics are different from those of glassy, pumiceous lava flows. They are closer to glacier dynamics, where most of the volume slides over a thin basal shear zone and till is generated there by abrasion and milling of the underlying layer. For the Grande Cascade lava flow, abrasion means that the flow lacks its classical blocky crust and instead the flow base is marked by a layer rich in fine-grained material. The structures and emplacement dynamics of this crystal-rich flow are consistent with ideal, gravity-driven shear flow. We thus argue for a global reassessment of silicic-rich lava emplacement based on crystal content and using a multidisciplinary approach focused on well-exposed examples in the rock record.

The epiphytic bryophyte succession of Buxus sempervirens forests in the Fırtına Valley, Rize (North Türkiye)

In this study, the epiphytic bryophyte succession of the Buxus sempervirens L. forests in Fırtına Valley (Çamlıhemşin-Rize, North Türkiye), one of the nine biodiversity hotspots in Türkiye, were investigated. For this purpose, a total of 60 sampling plots were taken from the live trunks of the B. sempervirens trees of different ages. Twenty-nine epiphytic bryophyte species were determined (24 mosses and 5 liverworts) within the sample plots. Also, six different life form types and four different habitat affinity categories were determined. The mat type life form is in the first place with 34.4% whereas the and cortico-saxicolous species are the most common with 51.7%. Two-Way Indicator Species Analysis (TWINSPAN) classified the epiphytic bryophyte communities on the trunks of the B. sempervirens at the second level into two main clusters (A and B) and three sub-clusters (A1, B1 and, B2). Detrended Correspondence Analysis (DCA) axis 1 was interpreted as gradient along the height of the epiphytic habitat (from the lower base to the upper zone) on trunks and the DCA axis 2 was interpreted as gradient of moisture (from mesic to xeric). Exsertotheca crispa (Hedw.) S.Olsson, Enroth & D.Quandt was the species with the highest Index of Ecological Significance (IES) value on the lower bases of the aged trees. Species diversity and epiphytic cover in the upper zones were lower than in the basal and middle zones in the study area. While Metzgeria furcata, (L.) Corda, Oxyrrhynchium hians (Hedw.) Loeske, Plagiothecium nemorale (Mitt.) A.Jaeger, and Radula lindenbergiana Gottsche ex C.Hartm were only found on old trees, Ctenidium molluscum (Hedw.) Mitt. and Pseudoleskeella nervosa (Brid.) Nyholm were only found on middle-aged trees.

Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat

ABSTRACT The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta’s sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11–12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.

Role of progesterone on dexamethasone-induced alterations in placental vascularization and progesterone receptors in rats†.

Intrauterine growth restriction (IUGR) is manifested by lower maternal progesterone levels, smaller placental size, and decreased placental vascularity indicated by lower expression of vascular endothelial growth factor (VEGF). Studies showed that progesterone increases angiogenesis and induces VEGF expression in different tissues. Therefore, the aim of the present study is to evaluate the effect of progesterone on placental vascular bed and VEGF expression and the modulation of nuclear and membranous progesterone receptors (PR) in dexamethasone-induced rat IUGR model. Pregnant Sprague-Dawley rats were allocated into four groups and given intraperitoneal injections of either saline, dexamethasone, dexamethasone, and progesterone or progesterone. Injections started on gestation day (DG) 15 and lasted until the days of euthanization (19 and 21 DG). Enzyme-linked immunosorbent assay was used to evaluate plasma progesterone levels. Real-time PCR and western blotting were used to evaluate gene and protein expressions of VEGF, and PR in labyrinth and basal placental zones. Immunohistochemistry was used to locate VEGF and different PRs in placental cells. Immunofluorescence was used to monitor the expression of blood vessel marker (αSMA). Dexamethasone decreased the vascular bed fraction and the expression of VEGF in both placental zones. Progesterone co-treatment with dexamethasone prevented this reduction. Nuclear and membrane PRs showed tissue-specific expression in different placental zones and responded differently to both dexamethasone and progesterone. Progesterone treatment improves the outcomes in IUGR pregnancy. Progesterone alleviated DEX-induced IUGR probably by promoting placental VEGF and angiogenesis.

Effect of Rhodomyrtus tomentosa Hassk. on HIF1α and VEGF expressions on hypertension placental

Context: HIF1α and VEGF are proteins marker oxidative stress and a decrease in placental growth factor (PlGF). Decreasing of HIF1α and VEGF in rats displayed poor trophoblast differentiation, placental abnormalities, and fetal mortality. Rhodomyrtus tomentosa is a flowering plant in the Myrtaceae family that has the potential to be a source of health-promoting chemicals. Aims: To analyze HIF1α and VEGF in serum and hypertension placental tissue after giving Rhodomyrtus tomentosa (RHO) leaves extract. Methods: Six treatments were given to the rats that were identified as being pregnant and pregnant rats with hypertension were given RHO with three doses: (a) normal pregnant rats (control); (b) hypertensive rats; (c) hypertensive rats + 100 mg/kg BW of RHO; (d) hypertensive rats +200 mg/kg BW of RHO; and (e) hypertensive rats + 400 mg/kg BW of RHO and (f) hypertensive rats + nifedipine. Under ketamine anesthesia, pregnant rats were removed on their 20th day of gestation. Immunohistochemistry and ELISA were used to assess HIF1α and VEGF protein expression. Results: There was a significant difference (p<0.01) in the expression of HIF1α and VEGF in the labyrinthine zone and yolk sac of the rat placenta between the normal (C-) and hypertensive (C+) groups. HIF1α and VEGF expression decreased when RHO was administered at doses ranging from 100 to 400 mg/kg BW. However, there was no significant change (p>0.05) in VEGF expression in the basal zone of the rat placenta across all groups. Conclusions: Rhodomyrtus tomentosa leaves extract decreases HIF1α and VEGF expressions in serum and repairs the tissue of the placenta's labyrinth, basal, and yolk sacs.

Congenital Rift Valley fever in Sprague Dawley rats is associated with diffuse infection and pathology of the placenta.

Rift Valley fever (RVF) is a disease of animals and humans associated with abortions in ruminants and late-gestation miscarriages in women. Here, we use a rat model of congenital RVF to identify tropisms, pathologies, and immune responses in the placenta during vertical transmission. Infection of late-gestation pregnant rats resulted in vertical transmission to the placenta and widespread infection throughout the decidua, basal zone, and labyrinth zone. Some pups from infected dams appeared normal while others had gross signs of teratogenicity including death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had widespread hemorrhage throughout multiple placenta layers. Teratogenic events were associated with significant increases in placental pro-inflammatory cytokines, type I interferons, and chemokines. RVFV displays a high degree of tropism for all placental tissue layers and the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. Given the potential for RVFV to emerge in new locations and the recent evidence of emerging viruses, like Zika and SARS-CoV-2, to undergo vertical transmission, this study provides essential understanding regarding the mechanisms by which RVFV crosses the placenta barrier.

Quantitative and geomorphologic parameterization of megaclasts within mass-transport complexes, offshore Taranaki Basin, New Zealand

Mass-transport complexes (MTCs) in sedimentary basins reflect the gravitational transport of sediments from the shelf edge to the abyssal plain. Megaclasts, large sedimentary blocks of hundreds of meters long within MTCs, can record kinematic and sedimentary information deemed essential to understanding source-to-sink systems. Yet, deformation structures in such megaclasts remain poorly understood. This study uses high-quality, three-dimensional (3-D) seismic reflection data from the deep-water Taranaki Basin offshore New Zealand to analyze the morphological character of 123 megaclasts and propose a new classification scheme based on their morphometric properties. The megaclasts are up to 400 m tall, 1900 m long, and 1200 m wide. In the study area, they are high- to moderate-amplitude features owing to their different lithologies and continuous-to-contorted seismic facies. The megaclasts can be classified as undeformed, rotated, deformed, and highly deformed based on their internal deformational styles. Two different kinds of morphological depressions observed on their basal shear zones further indicate whether the megaclasts are transported or formed in situ. Our study demonstrates that quantitative parameterization of the megaclasts provides important information about their deformational processes and a more complete understanding of megaclast emplacement along continental margins.

Penetrative Strain and Partitioning of Convergence‐Related Shallow Crustal Shortening, Across Scales, in the Lesser‐ and Sub‐Himalayan Thrusts: Insights From the Eastern Himalaya, Sikkim

AbstractShortening estimates from regional balanced cross‐sections remain lower than the predicted shortening from paleomagnetism and area‐balancing methods in the Himalaya. To reconcile this shortening deficit, we evaluate the shortening contribution from the often‐ignored penetrative strain of quartz grains and integrate these results with two published regional balanced cross‐sections from Sikkim Himalaya. Penetrative strain progressively decreases from the internal to the external thrusts with changing deformation conditions. Strain increases toward the basal thrust zone within each thrust indicating strain localization. Strain ellipsoids are folded along with the thrusts indicating the strain initiated before thrusting and folding. The layer‐normal shortening (LNS) strain dominates the internal thrusts. A combination of LNS and layer‐parallel shortening (LPS) strain exist in the low‐strained external thrust sheets. Approximately 78–91 km of shortening is recorded as penetrative strain in the Lesser‐ and Sub‐Himalayan thrusts. Lateral structural variations in the thrusts are reflected in the thrust‐sheet scale shortening and in the strain ellipsoid orientations, but not in the grain‐scale shortening. Shortening is partitioned differently across scales; the duplex records the highest thrust‐sheet scale shortening, while the roof thrust toward the hinterland records the highest grain‐scale shortening. Due to the dominance of LNS strain, removing strain from thrusts will collectively decrease ∼54–59 km of base lengths, thereby reducing the total minimum shortening of the Sikkim Himalaya by ∼13%. Therefore, the penetrative strain does not contribute to the shortening deficit in the Sikkim Himalaya.

The use of microplastics as a reliable chronological marker of the Anthropocene onset in Southeastern South America

Microplastics (MPs) represent an emergent contamination marker. For this reason, we analyzed the vertical distribution of MPs in six sediment cores retrieved from the Patos-Mirim System, the world's largest coastal lagoonal system. The sediment cores span from mid Holocene to present times according to both radiocarbon and lead dating and are located close to both urban/industrial and agricultural regions. We identified a basal pre-disturbance MP-free zone in all cores and an uppermost contaminated 70-cm-zone, where a general increasing trend in MPs content resembling the human anthropization process was recorded. The predominant format of MPs was fiber, followed by fragments. The most commonly identified polymers were rayon, PVC, acrylate, polycarbonate and cellophane. Urban/industrial and agricultural activities were shown as clear sources of MPs, leading to comparable MPs concentration values in the sediment cores. Thus, MPs are collectively a reliable indicator of the Anthropocene onset, and in the Patos-Mirim System the most appropriate chronology can be assigned to the beginning of 1970s, matching the intensification of anthropogenic activities in the area.

Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE is one of the leading causes of chronic refractory dysphagia in adults and children. EoE is a clinicopathologic disorder and the histological portion of the diagnosis requires enumerating the density of esophageal eosinophils in esophageal biopsies, and evaluating additional features such as basal zone hyperplasia is helpful. However, this task requires time-consuming, somewhat subjective manual analysis, thus reducing the ability to process the complex tissue structure and infer its relationship with the patient's clinical status. Previous artificial intelligence (AI) approaches that aimed to improve histology-based diagnosis focused on recapitulating identification and quantification of the area of maximal eosinophil density, the gold standard manual metric for determining EoE disease activity. However, this metric does not account for the distribution of eosinophils or other histological features, over the whole slide image. Here, we developed an artificial intelligence platform that infers local and spatial biomarkers based on semantic segmentation of intact eosinophils and basal zone distributions. Besides the maximal density of eosinophils [referred to as Peak Eosinophil Count (PEC)] and a maximal basal zone fraction, we identify the value of two additional metrics that reflect the distribution of eosinophils and basal zone fractions. This approach enables a decision support system that predicts EoE activity and potentially classifies the histological severity of EoE patients. We utilized a cohort that includes 1,066 biopsy slides from 400 subjects to validate the system's performance and achieved a histological severity classification accuracy of 86.70%, sensitivity of 84.50%, and specificity of 90.09%. Our approach highlights the importance of systematically analyzing the distribution of biopsy features over the entire slide and paves the way toward a personalized decision support system that will assist not only in counting cells but can also potentially improve diagnosis and provide treatment prediction.

Implementation and Assessment of Lung Ultrasound Training Curriculum for Physiotherapists With a Focus on Image Acquisition and Calculation of an Aeration Score.

Described here is the implementation of a lung ultrasound course for physiotherapists focused on the acquisition and retention of knowledge and skills. Initially, we provided online lectures in a virtual learning environment (VLE), in which we taught the semiquantification of edema through a lung ultrasound score (LUS). Afterward, the physiotherapists participated in face-to-face lectures (which resumed the online lectures), followed by hands-on training and simulation with ultrasound. We assessed knowledge acquisition through a multiple-choice test with 30 questions (totaling 10 points). The test was applied before accessing the VLE (pre-VLE), before the face-to-face course and at its end (pre- and post-course). Physiotherapists collected actual patients' ultrasound scans, which were uploaded to the VLE and assessed by three supervisors, who performed a consensus LUS calculation and gave virtual written feedback. Thirteen physiotherapists collected 59 exams. The test results were 3.60 ± 1.58 (pre-VLE), 5.94 ± 1.45 (pre-course) and 8.50 ± 0.71 (post-course), with p < 0.001 for all. The intraclass correlation coefficient for LUS between physiotherapists and supervisors was 0.814 (p < 0.001), with moderate-to-weak agreement for LUS of the lung apical, median and basal zones, with κ=0.455.334, and 0.417 (p < 0.001 for all). Trainees were found to have increased short-term acquisition and retention of knowledge and skills, with a good intraclass correlation coefficient between them and the consensus of supervisors for the LUS of actual patients.

S2362 Paraneoplastic Mucous Membrane Pemphigoid: Not Your Typical Cause of Odynophagia

Introduction: Paraneoplastic Mucous Membrane Pemphigoid (MMP) is a rare inflammatory autoimmune disorder that primarily affects the oral, ocular and aerodigestive mucous membranes and is associated with an underlying malignancy. IgG, IgA, and C3 autoantibodies target basal membrane zones causing subepithelial blisters with erosive lesions in the mucosa. It is rarely seen in the clinical setting, with an incidence of 2-10 cases in 100,000 individuals. High clinical suspicion is needed in order to diagnose Paraneoplastic MMP presenting as odynophagia and dysphagia. Case Description/Methods: A 88 year old female presented with a 5 month history of worsening odynophagia, dysphagia to solids and liquids and a fifty pound weight loss. Physical examination was remarkable for diffuse erosive lesions of the oral mucosa, tense bullae on the soft palate, and bilateral temporal symblepharon along with inflammation of upper and lower eyelids. Laboratory workup demonstrated elevated Cancer Antigen-125 (574.20 U/mL). Immunofluorescence study of biopsies taken from esophageal mucosa, right lateral tongue lesions and the left inferior conjunctiva were remarkable for IgG, IgM, IgA interkeratinocytic deposits at lower level of the epidermis and C3 linear deposits at the dermoepidermal junction consistent with Paraneoplastic Mucous Membrane Pemphigoid. Chest-abdominal-pelvic computed tomography scan demonstrated an irregular enhancing right adnexal mass, intra-abdominal lymphadenopathy, left hemiabdomen omental metastatic deposits and bilateral pulmonary nodules. Computed tomography guided core biopsy of a left omentum deposit was remarkable for primary ovarian metastatic high grade serous carcinoma. Due to refractory odynophagia and dysphagia, intravenous Solumedrol was initiated with subsequent improvement of symptoms. Patient was discharged with multidisciplinary team follow up for chemotherapy initiation and Rituxan induction. Discussion: Paraneoplastic MMP is an uncommon autoimmune mucocutaneous disease diagnosed when there is presence of stomatitis, histologic features of acantholysis or interface dermatitis, demonstration of anti-plakin autoantibodies on biopsy, with an underlying neoplasm. Less than 500 cases have been reported where clinical features, presentation, and autoantibodies profiles have varied widely between patients highlighting the challenge of diagnosis. Early recognition of Paraneoplastic MMP presenting as odynophagia is difficult due to the overlap of symptoms in more prevalent conditions.

ELECTROFACIES DEFINITION AND ZONATION OF THE LOWER CRETACEOUS BARRA VELHA FORMATION CARBONATE RESERVOIR IN THE PRE‐SALT SEQUENCE OF THE SANTOS BASIN, SE BRAZIL

Lower Cretaceous carbonates in the pre‐salt succession in the Santos Basin, eastern Brazil, are highly heterogeneous in terms of their reservoir characteristics as a result of depositional and diagenetic factors. Electrofacies have widely been used for reservoir zonation and, when allied with computer‐based methods such as neural networks, may help with the study of such complex reservoir rocks and with the identification of high‐quality reservoir zones. In this work, an unsupervised artificial neural network known as a self‐organizing map (SOM) was used to carry out a zonation of the pre‐salt carbonates in the Aptian Barra Velha Formation, the main reservoir unit in the Santos Basin. Available data included gramma‐ray, neutron porosity, resistivity deep, sonic, density, photoelectric factor, total porosity and effective porosity profiles from 21 wells together with mineralogical models. Core descriptions and thin section images were used as additional data for the lithological characterization of the electrofacies and consequently for reservoir zonation. A total of four electrofacies were defined from the SOM application, and five reservoir zones were identified.The characterization of the reservoir zones also considered the structural locations of the wells based on the relative depth to top‐ Barra Velha Formation; well locations were classified as structurally high, intermediate or low. Based on the reservoir zone characteristics, the results could be correlated with zonations in previous studies. A general tendency was noted for there to be an increase of finer‐grained sediments in the formation in wells located in structural lows; packstone and mudstone facies were prevalent in these wells and were in general characterized as poor‐quality reservoir rocks. By contrast, the shrubstones and grainstones which were more frequent in structurally high wells comprised higher quality reservoir rocks.The basal reservoir zone showed wide lithological variation compared to the overlying reservoir zones. Grainstone‐dominated facies were identified in the middle of the formation, and the uppermost reservoir zones were characterized by an upward increase in shrubstones and reworked grainstones which in general pointed to better quality reservoirs.

233. ENDOSCOPIC REFERENCE SCORE AND HISTOLOGICAL SCORING SYSTEM ARE COMPLEMENTARY ASSESSMENTS FOR CHARACTERIZING FIBROSTENOTIC OR INFLAMMATORY PHENOTYPES IN EOSINOPHILIC ESOPHAGITIS PATIENTS

Abstract The Histologic Scoring System (HSS) assesses severity/extent of histologic features (eosinophil density [ED]/basal zone hyperplasia [BZH]/eosinophil abscesses [EA]/eosinophil surface layering [SL]/surface epithelial alteration [SEA]/dyskeratotic epithelial cells [DEC]/dilated intercellular spaces [DIS]/lamina propria fibrosis [LPF]) in eosinophilic esophagitis (EoE). The Endoscopic Reference Score (EREFS) assesses endoscopic feature severity (edema/exudates/furrows/rings/strictures). We correlated HSS components with inflammatory/remodeling EREFS components in placebo-treated EoE patients from 2 trials—phase 2 proof-of-concept (POC; NCT02379052), phase 3 TREET part A (Phase3-PartA; NCT03633617). POC was a 12-week trial in adults, and Phase3-PartA was a 24-week trial in adults and adolescents. Proximal/mid/distal esophagus biopsies were collected at baseline/end of treatment (EOT) and scored by HSS for grade (severity)/stage (extent)/components (higher scores = greater severity). Endoscopies were scored by EREFS (higher scores = greater severity) and inflammatory (edema+exudates+furrows) and remodeling (rings+stricture) subscores calculated. Pearson correlation and single co-variate regression model analyses were performed between baseline HSS grade/stage, total/individual components scores and EREFS total/components scores and subscores, and for the change in scores from baseline at EOT (ΔEOT). Moderate-to-strong correlations (r > 0.3) were observed between total EREFS and HSS grade/stage for baseline/ΔEOT in POC and baseline in Phase3-PartA (Table). Moderate correlations were observed between BZH and EREFS remodeling subscore and rings for ΔEOT in Phase3-PartA; DIS grade and EREFS remodeling subscore and strictures for baseline and ΔEOT in POC but not Phase3-PartA; and EREFS inflammation and remodeling subscores and components for SEA and SL at baseline and ΔEOT in POC. Moderate-to-strong correlations were observed between EREFS inflammation subscore and DIS stage and between edema and DIS grade/stage at baseline in both studies. Similar results were observed using regression analyses. Specific components of HSS and EREFS, reflecting inflammatory and remodeling processes, are closely correlated, when examined by Pearson correlations or regression analyses, and can aid identification of fibrostenotic or inflammatory phenotypes in EoE. Correlations of DIS with endoscopic inflammatory and remodeling features reflect the role of barrier dysfunction in maintaining chronic inflammation that ultimately leads to remodeling.

Ventrolateral Prefrontal Cortex Contributes to Human Motor Learning.

This study assesses the involvement in human motor learning, of the ventrolateral prefrontal cortex (BA 9/46v), a somatic region in the middle frontal gyrus. The potential involvement of this cortical area in motor learning is suggested by studies in nonhuman primates which have found anatomic connections between this area and sensorimotor regions in frontal and parietal cortex, and also with basal ganglia output zones. It is likewise suggested by electrophysiological studies which have shown that activity in this region is implicated in somatic sensory memory and is also influenced by reward. We directly tested the hypothesis that area 9/46v is involved in reinforcement-based motor learning in humans. Participants performed reaching movements to a hidden target and received positive feedback when successful. Before the learning task, we applied continuous theta burst stimulation (cTBS) to disrupt activity in 9/46v in the left or right hemisphere. A control group received sham cTBS. The data showed that cTBS to left 9/46v almost entirely eliminated motor learning, whereas learning was not different from sham stimulation when cTBS was applied to the same zone in the right hemisphere. Additional analyses showed that the basic reward-history-dependent pattern of movements was preserved but more variable following left hemisphere stimulation, which suggests an overall deficit in somatic memory for target location or target directed movement rather than reward processing per se. The results indicate that area 9/46v is part of the human motor learning circuit.