Oclacitinib therapy in two cats with refractory proliferative and necrotising otitis externa.

Feline proliferative and necrotising otitis externa (PNOE) is a rare immune-mediated condition, usually self-limiting or responsive to immunosuppressants such as topical tacrolimus. This case report describes two cats with refractory PNOE that responded successfully to oclacitinib. One cat also had middle ear involvement and the other cat had extra-auricular dermatitis.

Multilocus Molecular Phylogeny of the Umbilicaria aprina Group (Umbilicariaceae, Lichenized Ascomycota) Supports Species Level and Neo-Endemic Status of Umbilicaria krascheninnikovii.

The Northeast Asian endemic species of lichen-forming fungus Umbilicaria krascheninnikovii is herein discussed in the global context of biogeography and phylogeny of the U. aprina group. The name U. krascheninnikovii has been erroneously used by lichenologists for Umbilicaria spp. from high latitudes or altitudes worldwide, as there are omphalodisc apothecia and rough "crystals" of a necral layer on the upper surface. To test the monophyly and phylogenetic relationships within the U. aprina group, four independent DNA regions (nrITS/5.8S, RPB2, mtLSU, and mtSSU) were used for six rare species, including a dozen specimens of U. krascheninnikovii from its locus classicus in Kamchatka. The study is based on the phylograms obtained using maximum likelihood and a Bayesian phylogenetic inference framework. As a result of phylogenetic and biogeographic analyses, it was shown that U. krascheninnikovii is a neo-endemic of the areas of modern volcanism in Kamchatka, Japan, as well as in the Kurile Islands, where this species was recorded for the first time. The morphology of U. krascheninnikovii is herein described and illustrated. Increasing the role of the sexual process and reducing asexual thalloconidiogenesis are shown to be apomorphic traits in the U. aprina group. The combination of sexual and asexual reproduction provides adaptive advantages in changing environmental conditions.

Figurate erythema in 11 Eastern European sphynx cats.

BACKGROUND: In humans, figurate erythema (FE) represents a heterogenous group of dermatoses with circular or serpiginous erythematous skin lesions; FE has not been reported in cats. OBJECTIVES: To report clinical and histological characteristics and outcomes of FE in sphynx cats from Baltic sea-bordering countries. ANIMALS: Eleven client-owned sphynx cats with FE. MATERIALS AND METHODS: We recruited cases meeting the following criteria: (i) a sphynx breed, (ii) FE with or without scaling, (iii) a chronic, waxing-and-waning course lasting longer than a month and (iv) an absence of other skin diseases. RESULTS: Of 11 cats, there were seven Donskoys, one Peterbald, one Ukrainian Levkoy and two presumed Canadian sphynxes; all except one were males, and the age of onset was <12 months in eight cats. Skin lesions lasted between 1.2 and 56 months, and they consisted of erythematous plaques with a linear-to-serpiginous, annular, gyrate or iris configuration predominating on the trunk and extremities. Scaling was often seen trailing the edge of the centrifugally expanding erythema. All cats were otherwise asymptomatic or mildly pruritic. Dermatophytosis was ruled out by special stains and/or fungal cultures in eight cats. Microscopic lesions revealed focal, mild-to-moderate epidermal hyperplasia and hyperkeratosis, minimal-to-mild dysplasia and subepidermal collagen smudging. Special stains were negative for dermatophytes. The clinical remission of FE was not achieved with diet changes or medical interventions; yet, a spontaneous, transient, partial or complete improvement occurred in most cats. CONCLUSION AND CLINICAL RELEVANCE: This is the first report of FE in sphynx cats from Eastern Europe.

Chromosomal Instability in Gastric Cancer: Role in Tumor Development, Progression, and Therapy.

According to the Cancer Genome Atlas (TCGA), gastric cancers are classified into four molecular subtypes: Epstein-Barr virus-positive (EBV+), tumors with microsatellite instability (MSI), tumors with chromosomal instability (CIN), and genomically stable (GS) tumors. However, the gastric cancer (GC) with chromosomal instability remains insufficiently described and does not have effective markers for molecular and histological verification and diagnosis. The CIN subtype of GC is characterized by chromosomal instability, which is manifested by an increased frequency of aneuploidies and/or structural chromosomal rearrangements in tumor cells. Structural rearrangements in the CIN subtype of GC are not accidental and are commonly detected in chromosomal loci, being abnormal because of specific structural organization. The causes of CIN are still being discussed; however, according to recent data, aberrations in the TP53 gene may cause CIN development or worsen its phenotype. Clinically, patients with the CIN subtype of GC demonstrate poor survival, but receive the maximum benefit from adjuvant chemotherapy. In the review, we consider the molecular mechanisms and possible causes of chromosomal instability in GC, the common rearrangements of chromosomal loci and their impact on the development and clinical course of the disease, as well as the driver genes, their functions, and perspectives on their targeting in the CIN subtype of GC.

Epigenomic Profiling Advises Therapeutic Potential of Leukotriene Receptor Inhibitors for a Subset of Triple-Negative Breast Tumors.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the LTB4R/LTB4R2 genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high LTB4R/LTB4R2 expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the LTB4R and LTB4R2 genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4, p = 2.6 × 10-6; R = -0.21, p = 0.015) and cg21886367 (R = -0.45, p = 7.3 × 10-8; R = -0.24, p = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated LTB4R. To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated LTB4R/LTB4R2 genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating LTB4R/LTB4R2 hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.

Adsorption Ability of Graphene Aerogel and Reduced Graphene Aerogel toward 2,4-D Herbicide and Salicylic Acid.

Within this work, new aerogels based on graphene oxide are proposed to adsorb salicylic acid (SA) and herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) from aqueous media. Graphene oxide aerogel (GOA) and reduced graphene oxide aerogel (rGOA) were obtained by freeze-drying processes and then studied by Raman spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET) analysis. The influence of contact time and the concentration of the adsorbates were also assessed. It was found that equilibrium for high adsorption is reached in 150 min. In a single system, the pseudo-first-order, pseudo-second-order kinetic models, Intraparticle diffusion, and Elovich models were used to discuss the detail of the aerogel adsorbing pollutant. Moreover, the Langmuir, Freundlich, and Temkin adsorption models were applied to describe the equilibrium isotherms and calculate the isotherm constants.

Histopathological characterisation of trunk-dominant canine pemphigus foliaceus, and comparison with classic facial and insecticide-triggered forms.

BACKGROUND: While the clinical features were described recently, the histopathological characterisation of trunk-dominant canine pemphigus foliaceus (PF) is lacking, and whether it differs from classic facial or insecticide-triggered PF is unknown. HYPOTHESIS/OBJECTIVES: This study describes the histopathological findings of trunk-dominant PF, and compares the results to classic facial and insecticide-triggered PF. ANIMALS: Skin biopsies from 103 dogs with clinically characterised trunk-dominant (n = 33), classic facial (n = 26) and insecticide-triggered PF (n = 44) were included. MATERIALS AND METHODS: Histological sections, randomised and blinded, were scored for over 50 morphological parameters of pustules, epidermis, dermis, adnexa and crusts. Intact pustule area and width were measured by digital microscopy. RESULTS: In trunk-dominant PF, 77 intact pustules were predominantly subcorneal (0.0019-1.940 mm2 area, 0.0470-4.2532 mm wide), and contained from one to over 100 acantholytic keratinocytes. Pustules had boat acantholytic cells, corneocytes, perinuclear eosinophilic rings, neutrophil rosettes, acantholytic cell necrosis, rafts, cling-ons and/or eosinophils. Peripustular epidermal spongiosis, necrosis and lymphocyte exocytosis occurred, as did follicular pustules. Mixed dermal inflammation often contained eosinophils. Trunk-dominant PF did not differ from the other PF groups except for few parameters, such as having fewer rafts (p = 0.003). Additional autoimmune inflammatory patterns occurred in all PF groups. CONCLUSIONS AND CLINICAL RELEVANCE: Trunk-dominant PF and other canine PF variants are histologically similar, which indicates shared pathomechanisms. The identification of common boat acantholytic cells and corneocyte separation has implications for the mechanisms of acantholysis. The diversity of histopathological and polyautoimmunity features support complicated immune mechanisms. Finally, results indicate that diagnostic biopsies cannot differentiate between these PF variants in dogs.

Highly Stable Docetaxel-Loaded Nanoparticles Based on Poly(D,L-lactide)-b-Poly(ethylene glycol) for Cancer Treatment: Preparation, Characterization, and In Vitro Cytotoxicity Studies.

Stability and narrow size distribution are among the main requirements that apply to drug formulations based on polymeric nanoparticles. In this study, we obtained a series of particles based on biodegradable poly(D,L-lactide)-b-poly(ethylene glycol) (P(D,L)LAn-b-PEG113) copolymers with varied hydrophobic P(D,L)LA block length n from 50 to 1230 monomer units stabilized by poly(vinyl alcohol) (PVA) by a simple "oil-in-water" emulsion method. We found that nanoparticles of P(D,L)LAn-b-PEG113 copolymers with relatively short P(D,L)LA block (n ≤ 180) are prone to aggregate in water. P(D,L)LAn-b-PEG113 copolymers with n ≥ 680 can form spherical unimodal particles with values of hydrodynamic diameter less than 250 nm and polydispersity less than 0.2. The aggregation behavior of P(D,L)LAn-b-PEG113 particles was elucidated in terms of tethering density and conformation of PEG chains at the P(D,L)LA core. Docetaxel (DTX) loaded nanoparticles based on P(D,L)LA680-b-PEG113 and P(D,L)LA1230-b-PEG113 copolymers were formulated and studied. It was observed that DTX-loaded P(D,L)LAn-b-PEG113 (n = 680, 1230) particles are characterized by high thermodynamic and kinetic stability in aqueous medium. The cumulative release of DTX from the P(D,L)LAn-b-PEG113 (n = 680, 1230) particles is sustained. An increase in P(D,L)LA block length results in a decrease in DTX release rate. The in vitro antiproliferative activity and selectivity studies revealed that DTX-loaded P(D,L)LA1230-b-PEG113 nanoparticles demonstrate better anticancer performance than free DTX. Favorable freeze-drying conditions for DTX nanoformulation based on P(D,L)LA1230-b-PEG113 particles were also established.

DNA Methylation and Prospects for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy for Triple-Negative and Luminal B Breast Cancer.

Despite advances in the diagnosis and treatment of breast cancer (BC), the main cause of deaths is resistance to existing therapies. An approach to improve the effectiveness of therapy in patients with aggressive BC subtypes is neoadjuvant chemotherapy (NACT). Yet, the response to NACT for aggressive subtypes is less than 65% according to large clinical trials. An obvious fact is the lack of biomarkers predicting the therapeutic effect of NACT. In a search for epigenetic markers, we performed genome-wide differential methylation screening by XmaI-RRBS in cohorts of NACT responders and nonresponders, for triple-negative (TN) and luminal B tumors. The predictive potential of the most discriminative loci was further assessed in independent cohorts by methylation-sensitive restriction enzyme quantitative PCR (MSRE-qPCR), a promising method for the implementation of DNA methylation markers in diagnostic laboratories. The selected most informative individual markers were combined into panels demonstrating cvAUC = 0.83 (TMEM132D and MYO15B markers panel) for TN tumors and cvAUC = 0.76 (TTC34, LTBR and CLEC14A) for luminal B tumors. The combination of methylation markers with clinical features that correlate with NACT effect (clinical stage for TN and lymph node status for luminal B tumors) produces better classifiers, with cvAUC = 0.87 for TN tumors and cvAUC = 0.83 for luminal B tumors. Thus, clinical characteristics predictive of NACT response are independently additive to the epigenetic classifier and in combination improve prediction.

Rheological Characterization and Printability of Polylactide (PLA)-Alumina (Al2O3) Filaments for Fused Deposition Modeling (FDM).

This article presents the study of the rheological properties and the printability of produced ceramic-polymer filaments using fused deposition method (FDM) 3D printing technology. Powder mixtures with an alumina content of 50 to 70 vol.% were fabricated by a wet processing route. A series of rheological experiments of the obtained mixtures were conducted in the temperature range from 200 to 220 °C for the commercial polylactide (PLA) powder and from 200 to 240 °C for ceramic-polymer, which corresponds to the recommended temperatures for 3D printing of commercial PLA filaments. The composition with the maximum content of alumina leads to a powdery material in which the molten polymer is insufficient to measure the rheological properties. In spite of this, the filaments were prepared from all the obtained mixtures with a tabletop single-screw extruder, the diameter and surface profile of which were analyzed. As the ceramic content increased, the diameter and surface roughness of the filaments increased. Therefore, it was only possible to print an object from a filament with the lowest ceramic content. However, the print quality of the 3D printed objects from the fabricated ceramic-polymer filament is worse (imperfect form, defects between layers) compared to the commercial PLA filament. To eliminate such defects in the future, it is necessary to conduct additional research on the development of printing modes and possibly modify the software and components of the 3D printer.

Peculiarities of γ-Al2O3 Crystallization on the Surface of h-BN Particles.

The main goal of the present work was to synthesize a composite consisting of h-BN particles coated with a γ-Al2O3 nanolayer. A method was proposed for applying nanocrystalline γ-Al2O3 to h-BN particles using a sol-gel technique, which ensures the chemical homogeneity of the composite at the nano level. It has been determined that during crystallization on the h-BN surface, the proportion of spinel in alumina decreases from 40 wt.% in pure γ-Al2O3 to 30 wt.% as a result of the involvement of the B3+ ions from the surface nitride monolayers into the transition complex. For comparison, nano-alumina was synthesized from the same sol under the same conditions as the composite. The characterization of the obtained nanostructured powders was carried out using TEM and XRD. A mechanism is proposed for the formation of a nanostructured γ-Al2O3@h-BN composite during the interaction of Al-containing sol and h-BN suspension in aqueous organic media. The resulting composite is a promising model of powdered raw materials for the development of fine-grained ceramic materials for a wide range of applications.

The Influence of Surface Texturing of Ceramic and Superhard Cutting Tools on the Machining Process-A Review.

Machining is an indispensable manufacturing process for a wide range of engineering materials, such as metals, ceramics, and composite materials, in which the tool wear is a serious problem, which affects not only the costs and productivity but also the quality of the machined components. Thus, the modification of the cutting tool surface by application of textures on their surfaces is proposed as a very promising method for improving tool life. Surface texturing is a relatively new surface engineering technology, where microscale or nanoscale surface textures are generated on the cutting tool through a variety of techniques in order to improve tribological properties of cutting tool surfaces by reducing the coefficient of friction and increasing wear resistance. In this paper, the studies carried out to date on the texturing of ceramic and superhard cutting tools have been reviewed. Furthermore, the most common methods for creating textures on the surfaces of different materials have been summarized. Moreover, the parameters that are generally used in surface texturing, which should be indicated in all future studies of textured cutting tools in order to have a better understanding of its effects in the cutting process, are described. In addition, this paper proposes a way in which to classify the texture surfaces used in the cutting tools according to their geometric parameters. This paper highlights the effect of ceramic and superhard textured cutting tools in improving the machining performance of difficult-to-cut materials, such as coefficient of friction, tool wear, cutting forces, cutting temperature, and machined workpiece roughness. Finally, a conclusion of the analyzed papers is given.

Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies.

BACKGROUND: A fast adoption of a non-invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. Firstly, in Russia according a new regulation it was possible to perform a widescale testing of pregnant women in chromosomal abnormality risk. The aim of the study-to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow. METHODS: Based on the first trimester combined prenatal screening results 12,700 pregnant women were classified as a high-risk (cut-off ≥ 1:100) and an intermediate-risk (cut-off 1:101 - 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results from intermediate-risk group were considered for invasive prenatal diagnostic. RESULTS: 258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations (p < 0.05) were revealed for fetal fraction (FF) and both for some patient's (body mass index and weight) and fetus's (sex and high risk of aneuploidies) characteristics. NIPT showed as a high sensitivity as specificity for common trisomies and SCAs with an overall false positive rate 0.3%. CONCLUSIONS: NIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown a high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women.

Granulation of Silicon Nitride Powders by Spray Drying: A Review.

Spray drying is a widely used method of converting liquid material (aqueous or organic solutions, emulsions and suspensions) into a dry powder. Good flowability, narrow size distribution, and controllable morphology are inherent in powders produced by spray drying. This review considers the granulation factors that influence the final properties of the silicon nitride dried powders. The first group includes the types of atomizers, manifolds, and drying chamber configurations. The process parameters fall into the second group and include the following: inlet temperature, atomizing air flow, feed flow rate, drying gas flow rate, outlet temperature, and drying time. Finally, the last group, feedstock parameters, includes many factors such as feed surface tension, feed viscosity, solvent type, solid particle concentration, and additives. Given the large number of factors affecting morphology, particle size and moisture, optimizing the spray drying process is usually achieved by the "trial and error" approach. Nevertheless, some factors such as the effect of a solvent, dispersant, binder, and sintering additives considered in the literature that affect the Si3N4 granulation process were reviewed in the work. By summarizing the data available on silicon nitride powder production, the authors attempt to tackle the problem of its emerging demand in science and industry.

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis.

In the last few years, more and more scientists have suggested and confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. This is particularly interesting for a better understanding of processes that occur in the development and progression of various diseases. Appearing on the preclinical stages of diseases, epigenetic aberrations may be prominent biomarkers. Being dynamic and reversible, epigenetic modifications could become targets for a novel option for therapy. Therefore, in this review, we are focusing on histone modifications and ncRNAs, their mutual regulation, role in cellular processes and potential clinical application.

Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of IL6, IL6R, TNFRSF1A, CTLA4, IL10, IL23R, and PADI4; and by RT-PCR for HLA-DRB1 and HLA-B. Associations of polymorphic variants with olokizumab efficacy according to the scores ACR20, ACR50, and DAS28-CRP were determined. We analyzed the obtained data by using logistic regression, ROC curves, and multivariate ANOVA. A high predictive value of the response to olokizumab therapy at 24 weeks was found for the combination of HLA-DRB1*04 and HLA-B*27 alleles with SNPs located in non-HLA genes (IL1B, IL17A, PADI4, DHODH, GLCCI1, IL23R, and TNFAIP3), and clinical characteristics (age, RA duration, and intensity) according to ACR20. Thus, the comprehensive assessment of polymorphic variants of HLA and non-HLA genes considering population characteristics in combination with clinical parameters allows for the elaboration of an RA prognostic panel.

Improving Burst Wave Lithotripsy Effectiveness for Small Stones and Fragments by Increasing Frequency: Theoretical Modeling and Ex Vivo Study.

Introduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying the BWL frequency may more effectively fragment stones to dust. Methods: A linear elastic theoretical model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone's size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1-5 mm) were treated at (1) 390 kHz, (2) 830 kHz, and (3) 390 kHz followed by 830 kHz. The mass of fragments >1 and 2 mm was measured over 10 minutes of exposure. Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of the composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at a higher frequency, but not at a lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p = 0.0003), whereas larger stones broke equally well to submillimeter dust at high, low, or mixed frequencies. Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.

Parental Origin of the RB1 Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma.

Our aim was to identify RB1 alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an RB1 mutation affects its phenotypic expression. By NGS and MLPA, RB1 mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified RB1 mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an RB1 mutation. Additionally, in two families with retinoblastoma history, mutations were inherited by probands from unaffected parents. Overall, nine probands inherited RB1 mutations from clinically unaffected fathers and five, from mothers. Yet, we gained explanations of maternal "unaffectedness" in most cases, either as somatic mosaicism or as clinical presentation of retinomas in involution, rendering the proportion of paternal to maternal truly asymptomatic mutation carriers as 9:1 (p = 0.005). This observation supports an assumption that parental origin of an RB1 mutation influences the likelihood of developing retinoblastoma. Additionally, our study revealed a relatively high frequency of asymptomatic carriage of the RB1 mutations among the parents of retinoblastoma patients, highlighting the utmost necessity of molecular analysis among the probands' relatives irrespective of their clinical status and family history of retinoblastoma.

Comorbidity of ectopic thymoma-associated exfoliative dermatitis and pemphigus foliaceus in a cat.

An 8-year-old cat was presented with pruritus, purulent paronychia, scaling, crusting, and spontaneous alopecia. Histopathology revealed intraepidermal neutrophilic pustular acantholytic dermatitis and hyperkeratotic cytotoxic interface dermatitis. No thoracic mass was seen on a lateral radiograph. Ectopic thymoma was discovered on necropsy. This case highlights the necessity for thorough investigation of any case of feline exfoliative dermatitis and pemphigus foliaceus for the presence of thymoma. Key clinical message: Comorbidity of exfoliative dermatitis and pemphigus foliaceus in a cat should prompt a thorough investigation for presence of a thymoma, possibly with advanced imaging techniques.

Comorbidité de dermatite exfoliative et de pemphigus foliacé associés à un thymome ectopique chez un chat. Un chat de 8 ans a été présenté avec prurit, panaris purulent, desquamation, croûtes et alopécie spontanée. L'histopathologie a révélé une dermatite acantholytique neutrophilique intra-épidermique et une dermatite d'interface cytotoxique hyperkératosique. Aucune masse thoracique n'a été observée sur une radiographie latérale. Un thymome ectopique a été découvert à l'autopsie. Ce cas met en évidence la nécessité d'une investigation approfondie de tout cas de dermatite exfoliative féline et de pemphigus foliacé pour la présence d'un thymome.Message clinique clé :La comorbidité d'une dermatite exfoliative et de pemphigus foliacé chez un chat devrait inciter à une enquête approfondie pour la présence d'un thymome, éventuellement avec des techniques d'imagerie avancées.(Traduit par Dr Serge Messier).

Mutations in Epigenetic Regulation Genes in Gastric Cancer.

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority (n = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority (n = 41), in histone modifier genes, among which mutations were most commonly found in KMT2D and KMT2C. Somatic mutations in KMT2D, KMT2C, ARID1A and CHD7 were mutually exclusive (p = 0.038). Mutations in ARID1A were associated with distant metastases (p = 0.03). The overall survival of patients in the group with metastases and in the group with tumors with signet ring cells was significantly reduced in the presence of mutations in epigenetic regulation genes (p = 0.036 and p = 0.041, respectively). Separately, somatic mutations in chromatin remodeling genes correlate with low survival rate of patients without distant metastasis (p = 0.045) and in the presence of signet ring cells (p = 0.0014). Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts.