Pathological Elements Research Articles

Clinical Potential of Misshapen/NIKs-Related Kinase (MINK) 1—A Many-Sided Element of Cell Physiology and Pathology

Clinical Potential of Misshapen/NIKs-Related Kinase (MINK) 1—A Many-Sided Element of Cell Physiology and Pathology

Mesh optimization for the virtual element method: How small can an agglomerated mesh become?

We present an optimization procedure for generic polygonal or polyhedral meshes, tailored for the Virtual Element Method (VEM). Once the local quality of the mesh elements is analyzed through a quality indicator specific to the VEM, groups of elements are agglomerated to optimize the global mesh quality. A user-set parameter regulates the percentage of mesh elements, and consequently of faces, edges, and vertices, to be removed. This significantly reduces the total number of degrees of freedom associated with a discrete problem defined over the mesh with the VEM, particularly for high-order formulations. We show how the VEM convergence rate is preserved in the optimized meshes, and the approximation errors are comparable with those obtained with the original ones. We observe that the optimization has a regularization effect over low-quality meshes, removing the most pathological elements. In such cases, these “badly-shaped” elements yield a system matrix with very large condition number, which may cause the VEM to diverge, while the optimized meshes lead to convergence. We conclude by showing how the optimization of a real CAD model can be used effectively in the simulation of a time-dependent problem.

Changes in Neuroimmunological Synapses During Cerebral Ischemia.

The direct interplay between the immune and nervous systems is now well established. Within the brain, these interactions take place between neurons and resident glial cells, i.e., microglia and astrocytes, or infiltrating immune cells, influenced by systemic factors. A special form of physical cell-cell interactions is the so-called "neuroimmunological (NI) synapse." There is compelling evidence that the same signaling pathways that regulate inflammatory responses to injury or ischemia also play potent roles in brain development, plasticity, and function. Proper synaptic wiring is as important during development as it is during disease states, as it is necessary for activity-dependent refinement of neuronal circuits. Since the process of forming synaptic connections in the brain is highly dynamic, with constant changes in strength and connectivity, the immune component is perfectly suited for the regulatory task as it is in constant turnover. Many cellular and molecular players in this interaction remain to be uncovered, especially in pathological states. In this review, we discuss and propose possible communication hubs between components of the adaptive and innate immune systems and the synaptic element in ischemic stroke pathology.

Investigating the incremental value of urine sediment reporting in emergency medicine with a Sysmex UN urinalysis system

Abstract Objectives Urinalysis is widely used and is also frequently requested in emergency situations for screening hypovolemia, urinary tract infections, diabetes, ketoacidosis and hematuria. Our aim was to evaluate the impact of reporting urinary sediment in emergency department specimens with the Sysmex UN system. Methods We evaluated urinalyses requested by the emergency department over a three-month period and examined red blood cell count interference, compared leukocyte esterase dipsticks to cytofluorimetric leukocyte count and nitrites to cytofluorimetric bacterial count. We then examined digital microscopy images to identify additional elements of interest or pathology. Results We collected 532 cases, 354 with only chemical and cytofluorimetric analysis and 178 with digital microscopy. Automated erythrocyte counting showed a 7 % error rate, mainly false-positive results. Leukocyte esterase had a sensitivity of 88.22 % and specificity of 88.84 % at the lower limit, while nitrites had a sensitivity of 41.06 % and a specificity of 99.38 %. Pathological elements were detected in 126 samples by digital microscopy: 70 had casts, 36 crystals and seven cells with high pathological value. Conclusions Evaluation of urine sediments by trained specialists can provide potentially important information even in emergency situations, whereby the pre-analytical phase must always be taken into account.

Paradoxes: Cholesterol and Hypoxia in Preeclampsia.

Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular disease (CVD) not only due to multiple shared pathologic elements but also because changes that develop over decades in CVD appear and resolve within days in preeclampsia. Those affected by preeclampsia and their offspring experience increased lifetime risks of CVD. At the systemic level, preeclampsia is characterized by increased cellular, membrane, and blood levels of cholesterol; however, cholesterol-dependent signaling, such as canonical Wnt/βcatenin, Hedgehog, and endothelial nitric oxide synthase, is downregulated indicating a cholesterol deficit with the upregulation of cholesterol synthesis and efflux. Hypoxia-related signaling in preeclampsia also appears to be paradoxical with increased Hypoxia-Inducible Factors in the placenta but measurably increased oxygen in maternal blood in placental villous spaces. This review addresses the molecular mechanisms by which excessive systemic cholesterol and deficient cholesterol-dependent signaling may arise from the effects of dietary lipid variance and environmental membrane modifiers causing the cellular hypoxia that characterizes preeclampsia.

A Novel Approach to Dual Feature Selection of Atrial Fibrillation Based on HC-MFS.

This investigation sought to discern the risk factors for atrial fibrillation within Shanghai's Chongming District, analyzing data from 678 patients treated at a tertiary hospital in Chongming District, Shanghai, from 2020 to 2023, collecting information on season, C-reactive protein, hypertension, platelets, and other relevant indicators. The researchers introduced a novel dual feature-selection methodology, combining hierarchical clustering with Fisher scores (HC-MFS), to benchmark against four established methods. Through the training of five classification models on a designated dataset, the most effective model was chosen for method performance evaluation, with validation confirmed by test set scores. Impressively, the HC-MFS approach achieved the highest accuracy and the lowest root mean square error in the classification model, at 0.9118 and 0.2970, respectively. This provides a higher performance compared to existing methods, thanks to the combination and interaction of the two methods, which improves the quality of the feature subset. The research identified seasonal changes that were strongly associated with atrial fibrillation (pr = 0.31, FS = 0.11, and DCFS = 0.33, ranked first in terms of correlation); LDL cholesterol, total cholesterol, C-reactive protein, and platelet count, which are associated with inflammatory response and coronary heart disease, also indirectly contribute to atrial fibrillation and are risk factors for AF. Conclusively, this study advocates that machine-learning models can significantly aid clinicians in diagnosing individuals predisposed to atrial fibrillation, which shows a strong correlation with both pathological and climatic elements, especially seasonal variations, in the Chongming District.

Pathological Elements Created by the Father Factor in Franz Kafka

The novels, stories, letters and aphorisms of Franz Kafka, one of the most famous writers of modern German literature, bear the traces of childhood trauma. Through his writing, Kafka revealed a system of thought that he was unable to express during his childhood. Franz Kafka grew up in a patriarchal family dominated by authority and misunderstanding. The sense of marginalisation he experienced within the family, combined with exclusion and misunderstanding, created an insensitivity, first to his immediate environment and then to the outside world, and restricted Franz's emotions from childhood. Unable to establish a positive relationship with his father, Kafka reflected in his works the feelings of alienation, hatred, inadequacy, complexes and insecurity that he had repressed in his unconscious because of his father's oppressive structure and exploitative behaviour. To date, research on Franz Kafka has focused on his works, but the unconscious behind these works has not been evaluated. The aim of this study is to examine the traumas created by the father phenomenon in the background of Franz Kafka's works, and the psychopathological elements created by these childhood traumas.

Correlation of Pathology and Homoeopathic Theory of Miasm

Hahnemann the father of homoeopathy lived in an age when the science of pathology was still in its primitive stage. It was since about two decades after the death of Hahnemann that the science of pathology started to progress by various scientists. Today we find pathology with facts and daily enriching itself with new ones. Many persisting old terms have mostly changed. The keen and logical observer Hahnemann observed and deduced many facts and conditions for expressing which the modern terms were not available with him so he had no way other than to use some descriptive phrases or to use the various terms in current parlance of his time for denoting his observed or deduced facts and conditions. In this article an attempt has been done to co-relate the homoeopathic concept of disease with modern concept of medicine. Thus is Greek theory of disease, pathos is a manifestation of three factors. 1] First of all disease involves a pathogen, the negative dynamic influence which disrupts the state of health. A pathogen may be a disturbing physical, environmental or psychological influence that affects any of the three levels of being. It includes the exciting causes of acute diseases as well as the fundamental cause of chronic diseases. 2] We have the disease process which is a combination of specific nature the pathogen and the general reaction of the vital force against it. This includes the progression of a disease through its natural stages and cycles. This is normally called pathology, which includes signs and symptoms. 3] Thirdly a disease includes Ponos, the Greek word for toil. This is the strain that the pathological process places on the constitution and its energy reserves as it fights to restore the state of health. The general were and tear on the organism due to continuous adaptive and defensive reactions of the vital force against pathogenic influence also produces concomitant symptoms in the organism. If a disruption of normal homeostasis remains unresolved it leads to disorders of the mind and all systems of the organism. Co-relation of Pathology and Homoeopathy: Hahnemann tells us in the Organon that the complete expression of every symptom is that of sensation, location, and modality. Location of symptom is an element in pathology and many times it is the sole element. Pathology is one of the symptoms of the disease, as well as any other of its manifestations and if we do not consider it we are not prescribing in accord with the totality of symptoms. We also do not individualize the case if we do not properly consider pathology. Remedies prescribed for the disease when there is present only one of the important elements of the prescription, namely a symptomatic similarity or a pathological similarity, cannot cure and all that can be expected of them is to relieve temporarily or to palliate. When we come across any disease condition as a Homoeopathic physician, two basic pathological conditions will be observed and they are Reversible pathology and Irreversible pathology. These pathological changes are further classified in to Inflammation, Proliferation and Degeneration. The detail understanding of nature and characteristics of each of them can be correlated with miasmatic diseases. Inflammatory changes and Theory of Miasm: All symptom syndrome where septicaemia or toxaemia are present having Psora in the background. Proloferative changes aand Theory of Miasm: All such subacute infalmmatory changes have psoric origin and end pathological changes are classified under sycosis miasmatic disease. Degenerative changes and Theory of Miasm: All such cellular changes indicate destruction in the background along wih the loss of normal structure and loss of normal functions which indicated syphilis miasmatic disease. Conclusion: on the basis of above discussion we conclude that 1. Pathology indicates pathogen, disease process and response of individual towards this process. 2. Psora, Sycosis and Syphilis are chronic miasmatic diseases. 3. Only nosological terminology is not sufficient to corelate the the hahnemannian concept of Miasm with pathology. The origin, development, stage of disease and clinical manifestations are to be considered while corelating the concept of miasm with pathology. Refrences: 1. Dey, Text book of Pathology, New Delhi. 2. Ortega, Notes on Miasm, B jain Publication, New Delhi. 3. Symposium Volumes, ICR Publications. 4. www. similia. Com.

Features of pharyngoscopic changes in the palatine tonsils

Diseases of the pharynx are a common pathology that doctors of various specialties encounter in everyday practice. Many of these diseases are difficult to diagnose although the pharynx is easily accessible for examination. The article describes the most frequently identified pharyngoscopic symptoms of diseases of the palatine tonsils: plaque, tonsillar detritus accumulation, tonsillar keratin cysts, asymmetry of the palatine tonsils, as well as the most important differential diagnostic signs that facilitate the interpretation of these symptoms in the diagnostic process. In addition, data from morphological studies of pathological elements of the tonsils are presented.

Use of minimally invasive ultrasound transducer during tubular microdiscectomy.

Minimally invasive ultrasound during tubular microdiscectomy is novel. The authors report the technique during surgery for L5-S1 herniated disc. Ultrasound provided real-time visualization of the pathology and neural elements. After discectomy and tactile assessment, ultrasound showed decompression of the thecal sac and traversing nerve root. The patient tolerated the procedure well, with resolution of preoperative pain and strength improvement. Postoperative MRI revealed a residual asymptomatic disc fragment that was retrospectively identified on ultrasonography. Minimally invasive ultrasound could become a useful supplement to direct visual and tactile assessment during tubular microdiscectomy, but further experience with surgical anatomy on ultrasound is required. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23206.

Bridging the Gap: Analyzing the Discrepancy Between Theoretical Knowledge and Clinical Implementation in Modern Caries Management in Existing Dental Education

Traditionally, caries has been addressed through surgical means, where the dentist utilizes rotary and hand instruments to eliminate the affected tooth tissue, creating a cavity that is subsequently filled with biomaterials for restoration purposes. This approach stems from the understanding of caries as an irreversible condition involving the destruction of hard tissues. However, recent evidence reveals caries to be a dynamic ailment characterized by alternating phases of demineralization and remineralization of hard tooth tissues. Contrary to the earlier perception, caries is now recognized as a dynamic disease with a fluctuating balance between factors that protect and promote tooth remineralization, as well as factors that contribute to tooth demineralization. Identified as caries risk factors and indicators, these pathological elements prompt a shift in perspective among cariologists towards managing caries through a medical model. In this medical model, caries is viewed as a multifactorial infectious disease caused by acidogenic bacteria present in the oral cavity. The recommended approach involves preventive strategies such as evaluating patients’ caries risk, regulating bacterial levels in saliva, employing various therapeutic agents, remineralizing incipient carious lesions and ultimately restoring cavitated lesions. These strategies not only emphasize prevention but also align with the principles of Minimal Intervention Dentistry (MID). Dental students studying in various dental institutions receive theoretical education on existing preventive caries management; however, the practical application of this knowledge is insufficient and requires emphasis through integration into the curriculum.

Fetal programming as a trend in modern medicine: Magnesium deficiency is the focus

In recent years, numerous studies have been carried out to identify the role of trace elements in pathology and clinical practice. Particular attention is paid to the role of maternal magnesium reserves during pregnancy, as a key factor in intrauterine development of the fetus and in postnatal life, as well as the consequences of maternal magnesium deficiency during pregnancy on health status at birth, in childhood and adulthood. To date, research has shown an association between magnesium deficiency and several conditions during pregnancy associated with high mortality and morbidity, such as gestational diabetes, preterm birth, preeclampsia, and small for gestational age infants or intrauterine growth restriction. Low maternal magnesium stores during pregnancy should be included among the many factors underlying fetal programming of disease in adults.

How does amyloid beta alter levels of ınflammation parameters in human astrocyte culture?

AbstractBackgroundIn neurodegenerative diseases, specific neuron types and glial cells undergo degeneration leading to the appearance of specific disease symptoms (1). Neurodegenerative diseases in the central nervous system (CNS) are also highly effective on cells that support neuron life. Astrocytes are dynamic support cells that maintain brain balance, regulate the neurotransmitter system, process synaptic information, energy metabolism, antioxidant system, and inflammatory response (2). The blood‐brain barrier (BBB) may lose its permeability in pathological conditions. Both endothelial cells and astrocytes undergo phenotypic changes and become reactive (3). In Alzheimer’s disease (AD), amyloid beta (Aβ) is suggested to induce a pathological pathway that leads to neurodegeneration and dementia (4). A limited number of studies in the literature reveal a general profile of the neuroinflammatory mediators induced by Aβ, one of the main pathological elements of AD in human astrocytes.MethodBased on this information, AD‐like pathology was created in our study with Aβ1‐42 treatment in human astrocyte cultures. The inflammatory response of these pathologies in human astrocytes was compared with the profile that emerges differently from a healthy astrocyte population. Alterations in the levels of released inflammatory proteins and their receptors were detected with the chemiluminescence‐based Western/dot blot method by using the human inflammation antibody array (Ray Biotech C‐Series Human Antibody Inflammation Array C4).ResultOur data show that Aβ1‐42 treatment predominantly releases IL‐6, MCP‐1, and TIMP‐2 proteins into the culture supernatant in human astrocyte cells. On the other hand, whether reactive astrogliosis was triggered in the presence of Aβ in human astrocytes was followed by immunofluorescent labeling (IF).ConclusionThis is the first study that investigated the general profile of released inflammatory factors in human astrocytes and how this profile is altered by Aβ1‐42 treatment.(The present work was supported by the Research Fund of Istanbul University, Project no: 30666)

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.

Complications after therapeutic plasma exchange within 24 hours

Background: By therapeutic apheresis is to remove a pathologic element from blood or to modulate cellular function. By this study we observed, complications after the therapeutic plasma exchange (TPE) within 24 hours with respect to patient’s demographic profiles and procedural variations. Methods: One-year prospective observational study conducted by the Department of Transfusion Medicine in collaboration with the Medicine Department, King George’s Medical University, Lucknow India. Results: In our study total of 60 cases and total of 150 TPE cycles were performed. Maximum mean age (36±4) was observed for cough and vomiting both and maximum mean BMI was observed followed for Infection at phlebotomy site (36.34±5.09). Maximum mean variation of hemoglobin was observed for vomiting (2.28±0.00), followed by internal bleeding. Maximum mean variation of activated partial thromboplastin time (aPTT) was observed for cough (22.05±0.34), followed by vomiting. Maximum mean variation of prothrombin time (PT) was observed for hypothermia (13.16±10.47), followed by internal bleeding. Maximum mean variation of S. creatinine was observed for abdominal discomfort (0.23±1.54), followed by vomiting. Maximum mean variation of systolic blood pressure (SBP) was observed for cough (7.00±5.20), followed by bipedal edema. Maximum mean variation of SpO2 was observed for death. Conclusions: Complication within 24 hours after the procedure was abdominal discomfort mainly in males with a correlation with body mass index (BMI). We observed significant positive association with complication versus APTT, PT, S. urea, S. creatinine, pulse, SBP, SpO2 and BMI. This emphasizes the decreasing trend of the complications with the increase in number of cycles.

Mitochondrial dynamics modulate the allergic inflammation in a murine model of allergic rhinitis.

Allergic rhinitis (AR) is a common allergic disorder, afflicting thousands of human beings. Aberrant mitochondrial dynamics are important pathological elements for various immune cell dysfunctions and allergic diseases. However, the connection between mitochondrial dynamics and AR remains poorly understood. This study aimed to determine whether mitochondrial dynamics influence the inflammatory response in AR. In the present study, we established a murine model of AR by sensitization with ovalbumin (OVA). Then, we investigated the mitochondrial morphology in mice with AR by transmission electron microscopy and confocal fluorescence microscopy, and evaluated the role of Mdivi-1 (an inhibitor of mitochondrial fission) on allergic symptoms, inflammatory responses, allergic-related signals, and reactive oxygen species formation. There was a notable enhancement in mitochondrial fragmentation in the nasal mucosa of mice following OVA stimulation, whereas Mdivi-1 prevented aberrant mitochondrial morphology. Indeed, Mdivi-1 alleviated the rubbing and sneezing responses in OVA-sensitized mice. Compared with vehicle-treated ones, mice treated with Mdivi-1 exhibited a reduction in interleukin (IL)-4, IL-5, and specific IgE levels in both serum and nasal lavage fluid, and shown an amelioration in inflammatory response of nasal mucosa. Meanwhile, Mdivi-1 treatment was associated with a suppression in JAK2 and STAT6 activation and reactive oxygen species generation, which act as important signaling for allergic response. Our findings reveal mitochondrial dynamics modulate the allergic responses in AR. Mitochondrial dynamics may represent a promising target for the treatment of AR.

Metacognitive interpersonal therapy-eating disorders versus cognitive behavioral therapy for eating disorders for non-underweight adults with eating disorders: study protocol for a pilot pre-registered randomized controlled trial.

Eating disorders (ED) are serious disorders characterized by an alteration of eating habits and excessive concern about weight and body shapes (Fairburn, 2002), accompanied by significant impairment inequality of life, high mortality rates and serious organic consequences (Jenkins et al., 2011; Treasure et al., 2015; 2020). Although evidence-based psychological therapies for nonunderweight ED presentations such as cognitive behavioral therapy for eating disorders (CBT-ED) are widely available, there is substantial scope for improvements, particularly in terms of efficacy and adherence. One option is to develop interventions to address elements of pathology not fully addressed by existing empirical supported treatments, such as incorporating techniques aimed at addressing interpersonal problems and personality disorder features into existing treatment delivery. We adapted Metacognitive Interpersonal Therapy, a psychological intervention supported by evidence for treating personality disorders and integrated it with existing CBT techniques for eating disorders (MIT-ED). MIT-ED targets aspects of ED that are not included in the transdiagnostic CBT-E model such as poor metacognition, or maladaptive interpersonal schemas. This is a pre-registered (Protocol number: 0000781) pilot randomized clinical trial aimed at assessing acceptability and feasibility of MIT-ED and establishing preliminary evidence of effectiveness for future larger studies. Twenty patients (10 in each arm) will be randomized to 20 sessions of individual psychotherapy, either MIT-ED or CBTE. Repeated follow-ups will be collected up to 24 months. Participants are recruited at a private outpatient clinic for ED treatment. Acceptability will be assessed via session attendance, completion rates and preliminary outcomes. The primary outcome is ED pathology assessed with the Eating Disorder Examination Questionnaire-6. Other ED outcomes assessed will be eating disorder attitudes, clinical impairment and binge eating pathology. Secondary treatment outcomes are anxiety, depression, and global symptomatology. We will also assess emotional awareness, emotion regulation and therapeutic alliance. Based on previous studies of MIT for personality disorders we hypothesize that MIT-ED will be acceptable to patients, evidenced by high treatment adherence and retention. We hypothesize that MIT-ED will be associated with reductions in eating disorder pathology, at least equivalent to CBT-E. Results will be used to inform the study design, sampling, likely effect sizes and choice of outcome measures for future larger trials of MIT-ED in ED samples.

Impact of Duration of Catheterization on the Success Rate of Trial Without Catheter in Acute Urinary Retention Due to Benign Prostatic Enlargement.

The most common cause of acute urinary retention in men over 50is benign prostate enlargement (BPE). Following the urethral catheterization, a trial without a catheter (TWOC) under the cover of alpha-blockers is given. The timing of TWOC varies from Day 3 to Day 7 of the retention episode. There is a need to study the improvement in the success rate of TWOC with the increasing number of days of catheterization. To measure the success rate of TWOC in acute urinary retention due to benign prostatic enlargement with increasing days of catheterization. The study was conducted in Social Security Teaching Hospital Lahore. Patients who presented with acute urinary retention due to benign prostatic enlargement were catheterized and given alpha-blockers. The patients were divided into two groups, one group having TWOC after three days and the other having TWOC after seven days. The success rate of TWOC was calculated and compared in the two groups. All patients included in the study had the first episode of acute retention with a moderately enlarged prostate and no element of second pathology or neurological deficit. A total of 48 patients were included in the study, divided into two groups of 24 patients each. In the first group who underwent TWOC after seven days of catheterization, 15 out of 24 patients had successful TWOC with a success rate of 62.5%. In the second group of 24 patients, who had TWOC after three days of catheterization, only 11 patients had successful TWOC with a success rate of 45.8%. There was a marked improvement in the success rate of TWOCwith increasing days of catheterization after an acute retention episode, secondary toBPE.

Retrospective analysis of the prevalence of diseases of the oral mucosa in the Volgograd region

The paper presents the results of a retrospective analysis of the prevalence of diseases of the oral mucosa. It is noted that the high prevalence of various ORS diseases is associated with a new coronavirus infection COVID-19 due to immunopathological changes in the patients body. It is known that patients with OOP diseases represent one of the most difficult groups of patients in dentistry. An increase in the frequency of occurrence of erosive-ulcerative lesions of the ROR was noted, which have different etiology and pathogenesis, while their clinical picture is quite similar. The study was carried out in the dental clinics of Volgograd clinical bases of the Department of Dentistry of the Institute of the NMFO FSBEI HE VolgGMU of the Ministry of Health of Russia. 2719 medical records of a dental patient (form 043y) were studied in the period 20192022. There was a significant dynamic growth, especially in 2022, of inflammatory-destructive pathologies of the COR, as well as the highest prevalence of COR pathologies in middle-aged people. A persistent increase in complicated cases with a generalized spread of pathological elements was revealed, which proves the relevance of searching for new methods for managing these patients.

SYMPTOM SEVERITY IN SCHIZOPHRENIA PATIENTS WITH NPAS3, DYSBINDIN-1 AND/OR TRIOBP PROTEIN PATHOLOGY IN THEIR BLOOD SERUM: A PANSS-BASED FOLLOW UP STUDY.

It has been proposed that aggregation of specific proteins in the brain may be a pathological element in schizophrenia and other chronic disorders. Multiple such aggregating proteins have now been implicated through post mortem investigation, including NPAS3 (Neuronal PAS domain protein 3), dysbindin-1 (encoded by the DTNBP1, Dystrobrevin Binding Protein 1, gene) and TRIOBP (Trio-Binding Protein, multiple isoforms). While the presence of protein aggregates in the brain is interesting in terms of understanding pathology, it is impractical as a biomarker. These proteins were therefore investigated recently in blood serum of schizophrenia patients and controls, showing patients to have higher levels of NPAS3 in their serum generally. TRIOBP-1 and dysbindin-1 were also found in an insoluble state, implying aggregation, but did not clearly corresponding to disease state. We revisit 47 of the originally recruited 50 patients with schizophrenia, all of whom are Croatian and aged between 18 and 72. We assessed their symptom specificity and severity using PANSS (the Positive and Negative Symptoms Scale), comparing those with NPAS3, insoluble dysbindin-1 and/or insoluble TRIOBP-1 in their blood serum to those lacking any such protein dysregulation. The frequency of each individual potential protein pathology among these patients was too low for meaningful statistical analysis, however the 11 patients that displayed one or more of these pathologies (NPAS3, dysbindin-1, TRIOBP-1 and/or TRIOBP-5/6) showed a subtle but significant increase in total PANSS scores compared to the 36 patients displaying none of the pathologies (p = 0.031), seemingly driven principally by increased scores on the general psychopathology scale. While the numbers of patients involved do not allow firm conclusions to be drawn at this time, this provides the first indication that disturbed proteostasis in blood serum, of proteins that aggregate in the brains of schizophrenia patients, may correlate with the severity of schizophrenia symptoms.