Manifestations Of Disease Research Articles

Comorbidity of inflammatory bowel diseases and periodontal pathology

Inflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, are a global disease of the 21st century. Periodontitis is the sixth most common disease in the world (second among dental pathologies after caries) and the leading cause of tooth loss in adults. At the beginning of the 21st century, the concept of “periodontal medicine” was formed, within the framework of which the bidirectional connection of periodontal pathology with systemic diseases of the body is considered. Extraintestinal manifestations of inflammatory bowel disease are associated with the generalized nature of the inflammatory response. In clinical guidelines, only aphthous stomatitis is described as a systemic manifestation of Crohn’s disease and ulcerative colitis from the oral cavity. Periodontitis is considered a less representative non-specific oral manifestation of inflammatory bowel disease. We searched the Pubmed and Scopus information databases for articles published before 02/15/2024 that examined the relationship between inflammatory bowel disease and periodontal pathology. The results of clinical studies, their synthesis in systematic reviews and meta-analyses, indicate a bidirectional relationship between Crohn’s disease and ulcerative colitis with periodontal pathology. The most likely mechanism is associated with a change in the microbiocenosis of the oral cavity and a further change in the intestinal microbiome due to oral intake of periodontal organisms, which leads to impaired intestinal permeability and the development of immune reactions that play a key role in the development of periodontal diseases and inflammatory bowel diseases.

Central retinal artery occlusion as the initial manifestation of mixed connective tissue disease in a young woman: a case report

BackgroundRetinal artery occlusions are rare amongst young adults, and relevant risk factors and etiology remain unclear. In this report, we present a case of central retinal artery occlusion (CRAO) as the initial manifestation of mixed connective tissue disease (MCTD) in a young woman.Case presentationA 22-year-old female presented to the emergency department with a sudden decrease in visual acuity in her right eye for 1 hour. She reported a similar episode in her left eye five years prior, which resolved spontaneously after 2 hours. Initially misdiagnosed with optic neuritis in the right eye at another hospital, she was referred to our institution the following day. Clinical examination revealed a CRAO in her right eye. A detailed medical history revealed that she had developed livedo reticularis (LR) on both lower limbs five years ago, which had been overlooked and untreated. Further rheumatologic history, hematologic tests, and an autoimmune work-up confirmed a diagnosis of mixed connective tissue disease (MCTD).ConclusionIn young patients presenting with CRAO, further examinations should be conducted to investigate systemic disease or an embolic source to prevent future sequelae.

Clinical manifestations of gastroesophageal reflux disease in medical university students

Clinical manifestations of gastroesophageal reflux disease in medical university students

Lipid droplet-associated proteins in alcohol-associated fatty liver disease: A proteomic approach.

The earliest manifestation of alcohol-associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol-induced changes in hepatic LD proteome as a function of LD size. Adult male Wistar rats (180-200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large-, medium-, and small-sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses. Morphological analysis of LD1-LD3 fractions of ethanol-fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different-sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large-sized LDs during the development of alcohol-associated hepatic steatosis. Several significantly altered proteins were identified in different-sized LDs isolated from livers of ethanol-fed rats. Ethanol-induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large-sized LDs in the liver.

Association of enthesitis with severity of psoriasis in psoriatic arthritis: an observational study.

The relationship between dermatological and articular manifestations of psoriatic disease remains incompletely elucidated. There is no strong correlation between the severity of cutaneous psoriasis and the clinical phenotypes of psoriatic arthritis (PsA). This study aims to examine the correlation between the severity of psoriasis and various clinical features, including measures of severity and activity of PsA, in a real-world clinical setting. Seventy-six consecutive adult patients of both genders with confirmed diagnoses of psoriatic arthritis (PsA) and psoriasis were included in the study. The Psoriasis Area and Severity Index (PASI) was assessed alongside various PsA variables: tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness, presence of dactylitis and number of affected digits, presence of enthesitis and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), patient's global assessment (PGA), and examiner's global assessment (EGA). Associations were analyzed using the Spearman correlation test and the Kruskal-Wallis test. Statistical significance was established at p = 0.05. Forty-two men and thirty-four women, median age of 56 (range 33-85) years, participated in the study. The median duration of psoriasis was 216 (range 0-600) months and median duration of PsA was 120 (range 7-456) months. There was no significant correlation between PASI and any PsA variables, except for the correlation between PASI and the presence of enthesitis (ρ = 0.285; p = 0.013). Moreover, older patients and patients with a long history of psoriasis manifested more often with enthesis as a sign of PsA. Our findings emphasize the correlation between the severity of psoriasis and presence of enthesitis in patients with PsA.

Yeast Solutions and Hyperpolarization Enable Real-Time Observation of Metabolized Substrates Even at Natural Abundance.

Metabolic changes in an organism often occur much earlier than macroscopic manifestations of disease, such as invasive tumors. Therefore, noninvasive tools to monitor metabolism are fundamental as they provide insights into in vivo biochemistry. NMR represents one of the gold standards for such insights by observing metabolites. Using nuclear spin hyperpolarization greatly increases the NMR sensitivity, enabling μmol/L sensitivity with a time resolution of about one second. However, a metabolic phantom with reproducible, rapid, and human-like metabolism is needed to progress research in this area. Using baker's yeast as a convenient metabolic factory, we demonstrated in a single study that yeast cells provide a robust and rapidly metabolizing phantom for pyruvate and fumarate, including substrates with a natural abundance of 13C: we observed the production of ethanol, carbon dioxide, bicarbonate, lactate, alanine from pyruvate, malate, and oxaloacetate from fumarate. For observation, we hyperpolarized pyruvate and fumarate via the dissolution dynamic nuclear polarization (dDNP) technique to about 30% 13C polarization that is equivalent to 360,000 signal enhancement at 1 T and 310 K. Major metabolic pathways were observed using tracers at a natural abundance of 13C, demonstrating that isotope labeling is not always essential in vitro. Enriched [1-13C]pyruvate revealed minor lactate production, presumably via the D-lactate dehydrogenase (DLD) enzyme pathway, demonstrating the sensitivity gain using a dense yeast solution. We foresee that yeast as a metabolic factory can find application as an abundant MRI phantom standard to calibrate and optimize molecular MRI protocols. Our study highlights the potential of using hyperpolarization to probe the metabolism of yeast and other microorganisms even with naturally abundant substrates, offering valuable insights into their response to various stimuli such as drugs, treatment, nourishment, and genetic modification, thereby advancing drug development and our understanding of biochemical processes.

Optic Chiasmitis as an Isolated Manifestation of Myelin Oligodendrocyte Glycoprotein-Associated Disease – a Case Report

IntroductionThe most common cause of chiasmopathy is compression of the optic chiasm by parasellar tumours. The tumours may produce any pattern of visual field defect depending on the tumour location and the patient’s chiasmal anatomy. Rare, non-compressive causes of chiasmopathy include, among others, infectious, post-infectious, inflammatory, autoimmune, demyelinating, toxic and ischaemic processes. Chiasmopathy can also occur due to trauma and radiation treatment.Case reportWe report a case of a 43-year-old patient who was admitted to our department because of a two-month history of headaches and constant, symmetrical blurriness over the temporal sides of vision. After a wide-ranging diagnostic process, the patient was diagnosed with an isolated optic chiasmitis in the course of myelin oligodendrocyte glycoprotein-associated disease, which is a rare, monophasic or relapsing, antibody-mediated inflammatory demyelinating disorder of the central nervous system.ConclusionsIt is crucial to remember that parasellar tumours are not the only cause of bitemporal hemianopsia. Patients with bitemporal hemianopsia, if there is no compressive lesion of the optic chiasm, should be investigated for optic chiasmitis. Optic chiasmitis is not a diagnosis in itself, but a sign of an underlying pathology, and during its evaluation should be treated as a variation of atypical optic neuritis. We hope that this ophthalmic manifestation of a rare neurological disease will make other clinicians aware of the utter importance of careful evaluation of visual disturbances.

Peculiar hyper vascular manifestations in idiopathic multicentric castleman disease without tafro syndrome: a case report.

Castleman disease affects lymph nodes with abnormal cell growth. It has unicentric (single node) Castleman disease (UCD) and multicentric (multiple nodes) Castleman disease (MCD) forms. MCD is systemic, with diverse symptoms, necessitating systemic treatment. Idiopathic MCD (iMCD) clinical subtypes are divided into iMCD- not otherwise specified (NOS) and iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticular fibrosis, organomegaly). UCD, iMCD-NOS, and iMCD-TAFRO mainly exhibit histopathology of hyaline vascular type, plasma cell type, and hyper vascular type, respectively. A 21-year-old female with no comorbidities presented to the outpatient department (OPD) with left inguinal swelling, gradually growing over four years, accompanied by fever and weight loss. Her past medical history included pulmonary TB 5 years prior and miscarriages. Vitals are within normal limits. Examination revealed a tender, nonreducible inguinal lump and a smaller neck swelling. Serological tests for infections were negative. Imaging revealed enlarged lymph nodes. Biopsy confirmed Castleman disease of the hyper vascular type. We performed surgical removal of the enlarged lymph nodes followed by close regular follow-up along with potential chemotherapy for relapse. Hyper vascular type of the lymph node histology in Idiopathic multicentric Castleman disease without TAFRO syndrome must be considered a differential diagnosis in lymphoproliferative disease.

Diagnosis of fungal diseases in quinoa (Chenopodium quinoa Willd) in Burkina Faso

Quinoa is an Andean pseudo-cereal crop that is mainly cultivated for its energy and protein-rich, gluten-free seeds. Quinoa is currently being popularized in Burkina Faso, but manifestations of fungal diseases have been observed on the plants. The aim of this study was to establish a causal relationship between the observed symptoms and the associated fungal pathogens. Samples of symptomatic organs were collected from the three agro-ecological zones and examined for fungal pathogen species via isolation on media. A total of six (6) diseases and twenty-nine (29) fungal species were described and identified in the collected organs. The diseases were present in the following proportions: (i) panicle browning followed by complete plant drying (45.36%), (ii) brown crown rot (41.20%), (iii) brown stalk rot (27.31%), (iv) damping-off (22.68%), (v) chlorosis with necrotic brown leaf spots (19.33%), and (vi) plant wilting (13.88%). The essential epidemiological factors of these pathologies are discussed.

Risk of Intestinal Complications, Extraintestinal Morbidity, and Mortality in Patients with Crohn’s Disease and Ocular Involvement

ABSTRACT Purpose Patients with Crohn’s disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease. Methods In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities. Results Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48–2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15–1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89–2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31–1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29–1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33–1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65–2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37–1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11–2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14–1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18–1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22–1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37–1.71, p < 0.001). Conclusions Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement.

The impact of war situation on endometriosis patients: Evaluating physical and mental health outcomes.

To investigate the impact of war situation on physical functioning, mental health status, and disease manifestations among endometriosis patients. Questionnaire-based study analyzing physical and psychosocial well-being. The study includes 50 endometriosis patients at Sheba Medical Center who completed a detailed questionnaire before and after the onset of the October 7, 2023, War in Israel. Significant deterioration in physical and mental health after the onset of war (pain score 6 vs 7; p < 0.001). Although having a first-degree relative affected by the war was associated with health deterioration (OR, 5.44; p = 0.02), similar pattern of health status aggregation was observed also in a subgroup of 19 women without family involvement, suggesting the general war situation as a likely cause. Starting new anti-anxiety or antidepressant medications and psychological therapy had a protective effect (OR, 0.21; p = 0.05). War situation exacerbates endometriosis symptoms, highlighting the importance of early psychological interventions to mitigate negative impacts.

Exposure to Gold Induces Autoantibodies against Nuclear Antigens in A.TL Mice.

To demonstrate causation or/and assess pathogenic mechanisms of environment-induced autoimmunity, various animal models that mimic the characteristics of the human autoimmune diseases need to be developed. Experimental studies in mice reveal the genetic factors that contribute to autoimmune diseases. Here, the immune response of two mouse strains congenic for non-H-2 genes, A.TL (H-2tl) and A.SW (H-2s), was evaluated after 15 weeks' exposure to gold aurothiomalate (AuTM). AuTM-treated A.TL mice showed anti-nuclear antibodies (ANA) with homogenous and/or fine speckled staining patterns and serum autoantibodies to ds-DNA, chromatin, histones, and ribonucleoproteins (RNP). Female A.TL mice showed a stronger immune response than males, as well as an increase of B cells in their spleen after 15 weeks of gold exposure. A.SW exposed for AuTM showed the induction of anti-nucleolar antibodies (ANoA) with a clumpy staining pattern, as well as an increase in splenic B and T cells. The serum autoantibodies levels in A.SW mice were limited compared to those of A.TL mice. Overall, A.TL presents a stronger immune response after gold exposure than A.SW. The immune response developed in A.TL presents similarities with the clinical manifestations in human autoimmune diseases. Thus, gold-exposed A.TL could constitute a potential experimental mouse model for the study of autoimmunity.

Infectious disease events in people with HIV receiving kidney transplantation: Analysis of the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study

BackgroundSince the implementation of universal antiretroviral therapy, kidney transplantation (K-Tx) has become a valuable option for treatment of end-stage kidney disease for people with HIV (PWH) with similar patient and graft survival as compared to HIV-uninfected patients. Little is known about the hazards and manifestations of infectious disease (ID) events occurring in kidney transplant recipients with HIV.MethodsUsing linked information collected in the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS), we described in-depth demographical and clinical characteristics of PWH who received a K-Tx since 2008. Further, we performed recurrent time to event analyses to understand whether HIV was an independent risk factor for ID events.ResultsOverall, 24 PWH with 57 ID events were included in this study (100% match of SHCS to STCS). Of these, 17 (70.8%) patients had at least one ID event: 22 (38.6%) viral (HIV not counted), 18 (31.6%) bacterial, one (1.8%) fungal and 16 (28.1%) probable infections. Most ID events affected the respiratory tract (25, 37.3%) or the urinary tract (13, 19.4%). Pathogen types and infection sites were similar in PWH and a matched control group of HIV-uninfected patients. HIV was not an independent risk factor for ID events (adjusted hazard ratio 0.94, p = 0.9).ConclusionBy linking data from two large national Swiss cohorts, we provided in-depth information on ID events in PWH receiving a K-Tx in Switzerland. HIV infection was not associated with an increased hazard for ID events after K-Tx.

Erdosteine in the treatment of acute and chronic diseases of the respiratory system: resolution of the scientific forum of experts “In the Spotlight”

Airway mucus hypersecretion is a pathophysiologic manifestation of acute and chronic airway inflammatory disease. Mucolytics can reduce mucus viscosity and promote mucus discharge and therefore can be considered pathogenetically based therapy.The purpose of this publication with the resolution of the scientific forum of experts was to discuss pharmacological features, efficacy, and safety of erdosteine.Results. Experts of thescientific forum not only reviewed the results of clinical trials, but also voted on the use of mucoactive drugs according to the principle of Delphi consensus. Comparison of the efficacy and safety of mucoactive drugs (erdosteine, acetylcysteine, carbocysteine, ambroxol) in patients with respiratory diseases by the experts during voting showed that the highest level of agreement among the experts was achieved for the drug Elmucin® (erdosteine) in terms of its mucolytic activity and other pharmacological features, as well as when discussing the safety of the compared drugs in the officially recommended doses. The highest level of agreement was also noted on the erdosteine efficacy in COPD patients in reducing the frequency and duration of disease exacerbations, as well as reducing the risk of hospitalization of COPD patients when used long-term as part of combination therapy. The demonstrated safety profile was the most beneficial among the reviewed mucoactive drugs.Conclusion. Elmucin® is a mucolytic with pleiotropic effects such as complex mucoactive action, potent antioxidant, anti-inflammatory and antibacterial activity with anti-adhesive effect for pathogens that determine its clinical efficacy in the treatment of acute and chronic airway diseases.

Pulmonary Rehabilitation for Diseases Other Than COPD.

Review the current literature regarding pulmonary rehabilitation (PR) for non-chronic obstructive pulmonary disease (COPD) diagnoses and what the evidence is regarding expected outcomes based on disease manifestations. Literature search was performed using PubMed database from March 2024 to June 2024. Terms included "pulmonary rehabilitation" and "exercise training" in conjunction with key words "interstitial lung disease (ILD)," "idiopathic pulmonary fibrosis," "asthma," "bronchiectasis," "post-acute sequalae of SARS-CoV-2 (PASC)," "long COVID," "pulmonary hypertension (PH)," and "lung cancer." Results were filtered for English language, randomized controlled trial, clinical trial, observational trial, meta-analysis, and guidelines. Emphasis was placed on more recent publications since prior reviews, where applicable. The abundance of literature involved ILD, where studies have demonstrated significant improvements in exercise capacity, health-related quality of life (HRQoL), and dyspnea, despite heterogeneity of diseases; benefits are similar to those seen with COPD. Those with milder disease have more sustained benefits longer term. Patients with asthma benefit in severe disease, lower exercise activity, elevated body mass index, or when comorbid conditions are present, and breathing exercises can improve symptoms of breathlessness. Patients with PASC have a multitude of symptoms and lack benefits in HRQoL measurements; PR improves performance on post-COVID-19 functional status scale, a more comprehensive measurement of symptoms. Those with bronchiectasis benefit from PR when airflow limitation or exacerbations are impacting symptoms and HRQoL. Those with stable PH can improve their exertional capacity without change in disease severity. PR reduces perioperative complications in those with lung cancer and preserve fitness during treatment.

Qingxin Jieyu Granule alleviates myocardial infarction through inhibiting neutrophil extracellular traps via activating ANXA1/FPR2 axis

BackgroundMyocardial infarction (MI), representing the most severe manifestation of coronary artery disease (CAD), stands as a primary concern in the prevention and management of cardiovascular diseases. Clinical evidence demonstrates that Qingxin Jieyu Granule (QXJYG) is efficacious in treatment of MI patients. However, the mechanisms underlying its therapeutic effects remain to be elucidated. PurposeThis study aimed to evaluate the effects of QXJYG on MI and investigate its underlying mechanisms. Materials and methodsThe MI model in rats was developed through ligating the left anterior descending (LAD) artery. The effect of QXJYG on cardiac function impairment in MI rats was assessed by echocardiography, while the improvement of cardiomyocyte morphology and myocardial fibrosis after treatment with QXJYG was evaluated through hematoxylin-eosin (H&E) staining and Masson staining. The chemical constituents of QXJYG in blood were identified by using the UPLC-Q-TOF/MS technique. Furthermore, the molecular mechanism underlying the QXJYG therapeutic effect in MI was postulated based on the disease gene-drug target network analysis. Other technical methods such as ELISA, immunohistochemical staining, Western Blot analysis and application of pharmacological inhibitors were employed to verify the effectiveness of QXJYG in treating MI and explore its potential molecular targets. ResultsThe cardiac function in experimental rats post-MI was significantly impaired, as evidenced by an enlarged infarction area, disordered arrangement of cardiomyocytes, and aggravated myocardial fibrosis. QXJYG treatment significantly enhanced the cardiac function and reduced the pathological damage of the cardiac tissue in MI rats. Through the network pharmacology analysis, we identified that FPR2 might be a potential target of QXJYG in its cardiac protection role. QXJYG markedly downregulated the level of neutrophil extracellular traps (NETs) in MI rats, specifically manifested as a significant reduction in the Histone-DNA level and expression of myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) proteins. Furthermore, QXJYG upregulated the levels of ANXA1 and FPR2 proteins in MI rats. The level of FPR2 was markedly reduced in MI rats upon administration of WRW4, a specific inhibitor of FPR2, which was associated with exacerbated MI injury and an elevated level of NETs. When WRW4 was co-administered with QXJYG, the cardioprotective effects of QXJYG on MI were significantly diminished. However, the addition of DNase I did not result in significant changes of the outcomes in MI rats after QXJYG intervention. ConclusionQXJYG treatment alleviates cardiac tissue injury in MI rats by inhibiting NETs through activating the ANXA1/FPR2 axis. The findings extend our understanding of the therapeutic effectiveness of QXJYG and offer a scientific foundation for the clinical utilization of QXJYG.

New Aspects of Mortellaro’s Disease: A Literature Review

Introduction. All over the word, hoof diseases, and Mortellaro’s disease in particular, are being among the most widespread and difficult to treat diseases in dairy cattle husbandry. They cause irreparable economic damage to the dairy industry by reducing the cattle reproductive ability indicators, feed conversion ratio, which compels to spend considerable amounts on treatment, prevention and culling of animals. Mortellaro’s disease is especially widespread in Europe and Western countries, but the current rate of national economy growth leads to the necessity to purchase the cattle abroad, which results in the increase of the Mortellaro’s disease incidence in Russia: at the farms where cattle has been imported, the percentage of the disease is 14.17±5.15% of the total number of hoof diseases in the herd. The aim of this review is to summarise the results of scientific research on the Mortellaro’s disease pathogenesis over the past 20 years.Materials and Methods. To achieve the stated objective, the criteria of inclusion into the search were defined. It was decided to include in the review the studies/reports presenting the results on: 1) the disease etiology and factors affecting the course of Mortellaro’s disease; 2) symptoms of Mortellaro’s disease manifestation in different species of farm animals; 3) the methods of Mortellaro’s disease treatment. The materials published in Elsevier, ASM Journal, Irish Veterinary Journal, Thieme, American Dairy Science Association, Epidemics, Schweiz Arch Tierheilkd, Journal of Clinical Microbiology, eLIBRARY.RU, Google Scholar have been investigated in the frame of the literature search. The search by the following keywords was done: interdigital dermatitis, Mortellaro’s disease, hoof diseases of cattle, contagious interdigital dermatitis. The time range of sources – those published within the period from 2003 to 2023.Results. In total, 44 articles have been analysed, 33 of which have been included in the present review. According to the studied materials, one of the prerequisites underlying the spread of Mortellaro’s disease in the Russian Federation is the import of the infected cattle, since the measures undertaken during the temporary housing and quarantine periods do not give the desired result. The animals get infected with the bacteria of the genus Treponema, which are localized deep in the hoof tissues, therefore, after the disease is endured, it turns into its chronic form. The specific symptoms of Mortellaro’s disease course in various cattle breeds have been established: in beef cows and buffaloes the interdigital dermatitis is characterised by a low level of pain symptom severity; in sheep – by the ulcerative lesions of the сoronary band, which progress and lead to the destruction of the abaxial hoof wall and loss of the hoof horn. The areas with the erosion are very painful, but the intercellular adhesive junctions are not lost, which allows for positive prognosis of the disease. The main indicators of productivity and fertility are reduced due to the disease, as is the immunity in general, and there is an estrous cycle delay. In the samples of patients sick with the digital dermatitis, an increase of the number of intact and degranulated mast cells is observed, compared to the healthy ones, which indicates that mast cells can play an important role in the pathogenesis of digital dermatitis. Nowadays, the Mortellaro’s disease treatment abroad and in Russia is based on the elimination of symptoms, and not the pathogen itself. The local treatment is mainly represented by the antiseptic baths, surgical treatment, local application of antibiotics to the wound. The experiments on antibiotic susceptibility of Treponema, which are the important step in the search for the specific treatment of Mortellaro’s disease, have been performed. The antibiotic susceptibility tests gave positive results (all isolates of Treponema were sensitive to tiamulin, valnemulin, tylosin, aivlosin, lincomycin, doxyclin), however, the difficulty lies in the method of drug administration into the source of Treponema localization, since the conventional ways of administration of antibiotics entail restrictions on the sale of milk and meat.Conclusion. The presented review of the scientific publications on Mortellaro’s disease made it possible to summarise the currently known results and identify the areas for further research. For example, it should be still investigated why the interdigital dermatitis requires the presence of many Treponema species rather than one? What role do representatives of the Mycoplasma, Porphyromonas and other bacteria play in the pathogenesis of the studied disease? And of course, there is a serious scientific gap in finding treatment of Mortellaro’s disease capable of eliminating the pathogen itself, rather than its symptoms. It should be mentioned that not all Treponema species can be cultivated, which also slows down the scientific process and makes the problem of Mortellaro’s disease treatment relevant worldwide.

ChatGPT M.D.: Is there any room for generative AI in neurology?

ChatGPT, a general artificial intelligence, has been recognized as a powerful tool in scientific writing and programming but its use as a medical tool is largely overlooked. The general accessibility, rapid response time and comprehensive training database might enable ChatGPT to serve as a diagnostic augmentation tool in certain clinical settings. The diagnostic process in neurology is often challenging and complex. In certain time-sensitive scenarios, rapid evaluation and diagnostic decisions are needed, while in other cases clinicians are faced with rare disorders and atypical disease manifestations. Due to these factors, the diagnostic accuracy in neurology is often suboptimal. Here we evaluated whether ChatGPT can be utilized as a valuable and innovative diagnostic augmentation tool in various neurological settings. We used synthetic data generated by neurological experts to represent descriptive anamneses of patients with known neurology-related diseases, then the probability for an appropriate diagnosis made by ChatGPT was measured. To give clarity to the accuracy of the AI-determined diagnosis, all cases have been cross-validated by other experts and general medical doctors as well. We found that ChatGPT-determined diagnostic accuracy (ranging from 68.5% ± 3.28% to 83.83% ± 2.73%) can reach the accuracy of other experts (81.66% ± 2.02%), furthermore, it surpasses the probability of an appropriate diagnosis if the examiner is a general medical doctor (57.15% ± 2.64%). Our results showcase the efficacy of general artificial intelligence like ChatGPT as a diagnostic augmentation tool in medicine. In the future, AI-based supporting tools might be useful amendments in medical practice and help to improve the diagnostic process in neurology.

Phosphorylation of Ser711 residue in the hypervariable region of zoonotic genotype 3 hepatitis E virus is important for virus replication.

Hepatitis E virus (HEV) is distinct from other hepatotropic viruses because it is zoonotic. HEV-1 and HEV-2 exclusively infect humans, whereas HEV-3 and HEV-4 are zoonotic. However, the viral and/or host factors responsible for cross-species HEV transmission remain elusive. The hypervariable region (HVR) in HEV is extremely heterogenetic and is implicated in HEV adaptation. Here, we investigated the potential role of Serine phosphorylation in the HVR in HEV replication. We first analyzed HVR sequences across different HEV genotypes and identified a unique region at the N-terminus of the HVR, which is variable in the human-exclusive HEV genotypes but relatively conserved in zoonotic HEV genotypes. Using predictive tools, we identified four potential phosphorylation sites that are highly conserved in zoonotic HEV-3 and HEV-4 genomes but absent in human-exclusive HEV-1 strains. To explore the functional significance of these putative phosphorylation sites, we introduced mutations into the HEV-3 infectious clone and indicator replicon, replacing each Serine residue individually with alanine or aspartic acid, and assessed the impact of these substitutions on HEV-3 replication. We found that the phospho-blatant S711A mutant significantly reduced virus replication, whereas the phospho-mimetic S711D mutant modestly reduced virus replication. Conversely, mutations in the other three Serine residues did not significantly affect HEV-3 replication. Furthermore, we demonstrated that Ser711 phosphorylation did not alter host cell tropism of zoonotic HEV-3. In conclusion, our results showed that potential phosphorylation of the Ser711 residue significantly affects HEV-3 replication in vitro, providing new insights into the potential mechanisms of zoonotic HEV transmission.IMPORTANCEHEV is an important zoonotic pathogen, causing both acute and chronic hepatitis E and extrahepatic manifestation of diseases, such as neurological sequelae. The zoonotic HEV-3 is linked to chronic infection and neurological diseases. The specific viral and/or host factors facilitating cross-species HEV infection are unknown. The intrinsically disordered HVR in ORF1 is crucial for viral fitness and adaptation, both in vitro and in vivo. We hypothesized that phosphorylation of Serine residues in the HVR of zoonotic HEV by unknown host cellular kinases is associated with cross-species HEV transmission. In this study, we identified a conserved region within the HVR of zoonotic HEV strains but absent in the human-exclusive HEV-1 and HEV-2. We elucidated the important role of phosphorylation at the Ser711 residue in zoonotic HEV-3 replication, without altering the host cell tropism. These findings contribute to our understanding the mechanisms of cross-species HEV transmission.

MDVarP: modifier ~ disease-causing variant pairs predictor

BackgroundModifiers significantly impact disease phenotypes by modulating the effects of disease-causing variants, resulting in varying disease manifestations among individuals. However, identifying genetic interactions between modifier and disease-causing variants is challenging.ResultsWe developed MDVarP, an ensemble model comprising 1000 random forest predictors, to identify modifier ~ disease-causing variant combinations. MDVarP achieves high accuracy and precision, as verified using an independent dataset with published evidence of genetic interactions. We identified 25 novel modifier ~ disease-causing variant combinations and obtained supporting evidence for these associations. MDVarP outputs a class label ("Associated-pair" or "Nonrelevant-pair") and two prediction scores indicating the probability of a true association.ConclusionsMDVarP prioritizes variant pairs associated with phenotypic modulations, enabling more effective mapping of functional contributions from disease-causing and modifier variants. This framework interprets genetic interactions underlying phenotypic variations in human diseases, with potential applications in personalized medicine and disease prevention.