Brain Gut Axis Conference

8th -9th October 2022, Zagreb, Croatia

The first student interdisciplinary conference on the Brain-gut axis in Croatia

Join us for two days of ground-breaking and curious lectures, workshops, posters, and social programs!

PROGRAMME OUTLINE

We are gathering Croatian pioneers and foreign experts with the aim of popularizing the topic and attracting young scientists to this field, allowing mobility within Croatia and Europe.

Lectures

We are gathering Croatian pioneers and foreign experts with the aim of popularizing the topic and attracting young scientists to this field, allowing mobility within Croatia and Europe.

Workshops

The workshops include interdisciplinary topics that are insufficiently covered in regular biomedical classes and play an important role in the career development of biomedical students. The goal is to provide students with the context of other disciplines and allow them to gather experience in new fields of neuroscience.


OUR ULTIMATE GOAL

We want to provide a framework for understanding the complexity of nervous and gastrointestinal interactions and raise awareness of the importance of proper perception of the whole organism and microbiota in the context of improving the research approach to neurological and psychiatric diseases and ultimately potential treatments.

Participation
(Croatian students)

25 €

  • Participation in a scientific program, plenary lectures and workshops

  • Book of abstracts, congress bag and materials

  • Certificate of participation

  • Coffee breaks & Meals

  • Social programme

Participation
(Foreign students)

30 €

  • Participation in a scientific program, plenary lectures and workshops

  • Book of abstracts, congress bag and materials

  • Certificate of participation

  • Coffee breaks & Meals

  • Social programme

  • Eligibility to apply for Home stay programme

Online participation

10 €

  • Participation in the plenary lectures and panel discussions

  • Certificate of participation

In-person lectures ONLY

10 €

  • Participation in the plenary lectures and panel discussions

  • Certificate of participation


Organizing team

Section for Neurobiology, Association of biology students "BIUS" Zagreb
Student Section for Neuroscience, School of Medicine, Zagreb
Youth Association for Personalized Medicine "PROMISE"
Association of Biotechnology students "UsbRi" Rijeka
Student Section for Gastroenterology and Hepatology, School of Medicine, Zagreb


Workshop mentors

Assoc. Prof. Dinko Mitrečić, MD, PhD
Croatian Institute for Brain Research, Zagreb
Executive and Management Board at European Union Joint Programme for Neurodegenerative Diseases

Andrea Gelemanović, MSc, PhD
Mediterranean Institute for Life Sciences, Split

Assoc. Prof. Marina Boban, MD, PhD
Department of Neurology, University Hospital Center,
School of Medicine, University of Zagreb

Blanka Roje, PhD, Laboratory for Cancer Research, School of Medicine, University of Split

Dinko Smilović, MD, PhD
Croatian Institute for Brain Research, Zagreb
Goethe University, Frankfurt

Ana Filošević, MSc, PhD
Department of Biotechnology, University of Rijeka

Andrija Štajduhar, Mag. Math, PhD
Department of Medical Statistics,
School of Medicine, University of Zagreb

Assoc. Prof. Jelena Osmanović-Barilar, MD, PhD
Laboratory of Neuropharmacology, Croatian Institute for Brain Research, Department of Pharmacology,
School of Medicine, University of Zagreb

Nikolina Pleić, PhD, Department of Medical Biology, School of Medicine, University of Split

Assoc. Prof. Goran Sedmak, MD, PhD
Head of the Department for Neurodevelopment
Croatian Institute for Brain Research, Zagreb

Assoc. Prof. Petra Korać, MSc, PhD
Department of Molecular Biology
Faculty of Science, University of Zagreb

Assoc. Prof. Željka Krsnik, MD, PhD
Croatian Institute for Brain Research,
School of Medicine, University of Zagreb

Jan Homolak, MD, Laboratory of Neuropharmacology, Croatian Institute for Brain Research

Eva Pavlinek, MSc, Exaltum, Zagreb


Research competition

Submit your research and win one of three prizes.


Homestay programme

The Homestay Program is a project created by the Brain-Gut Axis Conference, which focuses on providing a cheaper and different way to accommodate international students who take part in this conference.


Social programme

After numerous interesting lectures and workshops, enjoy our city and social workshops we have prepared for you to gain new friends and forge international acquaintances while experiencing something new.


Partner Institutions and Sponsors

School of Medicine, University of Zagreb

Zagreb Tourist Board

Institute for Medical Research and Medicine of Work

School of Medicine, University of Split

Croatian Institute for Brain Research Zagreb

MEDizzy

JANAF

Student Council, Faculty of Science, University of Zagreb

Mediterranean Institute for Life Sciences Split

Mindset Health

Ken Hub

Department of Biotechnology, University of Rijeka

Croatian Pharmacological Society

Next Bike

Partner conferences

Mosa Conference

GSC Belgrade

NeuRI Rijeka

INAMSC Jakarta

SAMED Sarajevo

OSCON Osijek

AMSC Antwerp

BioPsy Koper

CROSS Zagreb

ICMS Sofia

Pharmion Mostar

SymBioSE

SISB Zagreb

iMED Lisbon

MIMS Podgorica

CPSA

Please feel free to contact us with any inquiries or trouble
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© Brain Gut Axis Conference Zagreb. All rights reserved.


Preliminary timetable

Lectures

Dr. Pierre Marie Lledo, PhD
The brain: A coincidence detector between sensory experiences and internal milieu

Dr. Kristina Endres, PhD
The microbiome in neurodegenerative diseases: Friend, foe or just affected?

Prof. Sahar El Aidy, PhD
Gut bacterial products of drug metabolism alter gut-brain cross-talk

Prof. Anne-Katrin Pröbstel, PhD
Microbiota-immune crosstalk in neuroinflammation

Dr. Blaženka Kos, PhD
Development of new generation of
probiotics as living medicines and their impact on the
intestinal microbiota

Prof. Vida Demarin, MD, PhD
Microbiota disregulation after stroke and its association with recovery outcome

Prof. Mladenka Tkalčić, PhD
Irritable bowel disease - A brain-gut miscommunication

Workshops

NeuroanatomyThis workshop will introduce participants to neuroanatomy, specifically the main anatomical areas of the brain and their connection to brain function. We will go through areas in charge of vision, hearing, logical and abstract reasoning, emotions, motivation, and memory, with a special focus on the interoperability of different brain systems that allow the seamless operation of these functions.

Neurohistology digitalizedDuring this workshop, participants will be able to learn the basics of human brain tissue fixation and
preparation for immunohistochemistry procedure. Moreover, immunohistochemistry and immunofluorescence protocols will be briefly explained. Participants will learn how to digitalize stained histological samples using the high-resolution slide scanner amammatsu 2.0 RS. Using the NDP.view 2 software for image analysis, neurohistological samples will be shown.

Research project proposal
The aim of this workshop is to show how to write research project proposals. Selected project proposals submitted to European and national funding organizations will be presented, and their strengths and weaknesses will be highlighted. Additionally, workshop participants will be actively involved in the planning and writing of the project proposal, as well as project review according to the given criteria.

Developing a scientific career pathAnxiety and depression in PhD students are worsening. Dedicated international conferences discuss the mental health of the next generation of researchers. It is clear that we need a systemic change in research cultures. Will you make the right or wrong career choice after your studies? How can you make informed decisions in different steps of your scientific path to be supported towards a successful research career? These are the core questions we will try to answer in this interactive workshop because in the journey to success, the choices we make affect how far we travel.

Probiotics - a small world under the microscopeProbiotics are an important part of our daily diet and contribute to preserving the "health" of our digestive system, but very often this topic is accompanied by numerous misconceptions. The workshop is designed with the aim of getting to know this topic more closely and discovering a completely new world. We are going to cover the basics of probiotics and prebiotics, how to distinguish them, and in which foods to find them, examine them under a microscope and participate in an educational quiz to test the acquired knowledge, but also reward the best participants.

Systematic Review and Meta-AnalysisIn order to obtain a state-of-the-art synthesis of the most recent research on a specific research question, systematic reviews and meta-analyses have grown in importance in healthcare settings. This is due to the explosion of the scientific literature and the fact that time is always limited (especially if you work in healthcare). Systematic reviews seek to identify, evaluate, and summarize the results of all relevant individual research on a given topic, making the available information more understandable to decision-makers. The purpose of this workshop is to familiarize the participants with the fundamental ideas of systematic reviews and meta-analyses, explaining their significance and outlining the methods and terminologies employed. This will give the participants the knowledge and skills necessary to identify and comprehend a reliable review.

Bioinformatics lab - TranscriptomicsThe goal of the transcriptomics workshop is to familiarize participants with the tools that are frequently used to analyze gene expression data, with an emphasis on RNA-seq data
interpretation. The theoretical underpinnings of the key ideas in RNA-seq data processing will be covered in this workshop, and hands-on activity will be planned using the web-based
Galaxy platform. The entire procedure—from obtaining raw RNA sequences, mapping, and quality control, to differential gene expression analysis and functional enrichment
analysis—will be walked through with participants. Participants will benefit from a practical session that will help them solidify their understanding of RNA-seq analysis ideas and talk about how to view and interpret the data.

Prevention of CVI with the emphasis on brain-gut axisStroke is one of the leading causes of death and disability in adults worldwide. With increasing life expectancy, it is expected that one of four persons now under the age of 25 will develop a stroke during their lifetime. Primary stroke prevention is a challenging opportunity so often misused by different campaigns that do not have a scientific background. However, evidence-based strategies are available and they should be implemented in practice. The aim of the workshop is to discuss possible
opportunities and obstacles in achieving optimal primary stroke prevention.

Lumbal PunctionIn this workshop students will get acquainted with the procedure of lumbar punction – what are the proper indications and contraindications for its use, and how
can the collected samples be used to diagnose various diseases. Finally, students will be able to try to perform the procedure itself on a model made exactly for the purpose of training young doctors in this life-saving procedure.

Neurologic ExamStudents are going to acquire valuable clinical knowledge in this workshop on how to examine a neurological patient systematically.

Introduction to stem cell researchIn this workshop, students will have the opportunity to acquire knowledge on the application of neural stem cells in neuroscientific research.

Bioninformatics Lab - MetagenomicsIn this workshop, we will go through the main concepts used in metagenomic analyses. We will talk about different approaches in metagenome sequencing and examine the workflows
and the tools used in the bioinformatics analysis and their real-world applications. Finally, the participants will have a hands-on practical work where they will be able to conduct the main steps in a metagenome analysis of gut microbiome using the free web-based tools.

Neurobiology of addiction on Drosophila melanogasterWorkshop Drosophila melanogaster – neurobiology of addiction will give an overview of established behavioural phenotypes associated with addiction to different classes of drugs. The focus will be on the molecular mechanism of psychostimulants in the brain, behavioural consequences of active and passive drug administration and the influence of feeding with polyphenols on monoamines and behaviour after drug administration. Attendance will have the opportunity to do simple hands-on experiments associated with substance addiction and learn the basics of Drosophila handling under laboratory conditions. We will discuss the use of Drosophila, as a model in basic research of different types of neurodegenerative diseases such as Parkinson’s and schizophrenia.

Abdominal UltrasoundAs this is regarded as one of the many useful and valuable techniques in medical education, we provide an opportunity to practice and upgrade the skill of quality, systematic and effective abdominal ultrasound that will be a valuable asset of each new young doctor's repertoire as a part of this workshop. In this workshop, we will cover the basics of abdominal ultrasound and how to use it to notice signs of emergent states associated with the abdomen. Take the chance to learn a valuable diagnostic skill or simply expand your knowledge of the medical field.

Introduction to R
This workshop will introduce participants to the widely used open source language – R. Using Rstudio - an integrated development environment (IDE) that provides an interface by adding many convenient features and tools, participants will learn the basic programming concepts and terminology of R. The workshop will cover the principles of R syntax, R packages, data exploration and data wrangling. R is best learned by solving practical problems, so each topic will be covered by a lecture, followed by a practical exercise. This workshop is intended for anyone interested in adding R to their skillset.
Topics:
• Using the console and assigning variables
• R packages
• Vectors, factors, data frames
• Exploring a given dataset
• Data wrangling

Biomedical Statistics in a NutshellStatistics will follow each young researcher in their path of scientific discoveries. Many students will go through education on this matter but the application of the statistical tools usually leaves many confused. This workshop will provide an overview on how to recognize analyses useful for a specific type of data and will remind students on how to assess their data in their future research.

Statistics and Machine Learning in Microbiome ResearchThe growing interest in microbiome research drives studies related to association and clinical use for diagnostics, prognostics, and therapeutics, yielding more and more information about the vital role of the microbiome in human health. Improved analytical tools are developed and used to exploit all information from these biological datasets. This workshop will go through the foundational concepts from the basics of statistical inference to modern machine learning and model explanation methods. We will investigate various research questions and statistical applications and demonstrate these concepts in hands-on examples that will help you navigate through modern quantitative research methods in the microbiome and other biomedical domains.

Deep Brain StimulationNeurosurgery has traditionally been a leader in advanced technologies, successfully adopting and adapting new techniques and devices in an effort to increase the safety and effectiveness of brain and spine surgery. Especially Deep Brain Stimulation (DBS) has evolved during the last decades and become a leading stereotactic technique for the treatment of Parkinson's disease, essential tremor, and dystonia, different psychiatric disorders such as obsessive-compulsive disorder and major depression, refractory epilepsy, and chronic pain syndromes. In addition, the potential DBS role for disorders of consciousness, Alzheimer’s disease, anorexia, obesity, addiction, traumatic brain injury, etc. is still being researched. As a procedure, DBS provides targeted circuit-based neuromodulation. Nowadays, DBS systems include an intracranial electrode, an extension wire, and a pulse generator. Software and hardware advances, as well as targeting advances occurring daily in functional neurosurgery enables improved accuracy of implanted electrodes, individualized therapy to patients, and less surgical intervention, improving overall the quality of patients' life. Due to proven good outcomes and technological development, a number of research has been conducted resulting in several approved targets for treating mentioned neurological and neuropsychiatric disorders, such as the subthalamic nucleus, the globus pallidus internus, ventral intermediate nucleus, anterior nucleus and centromedian-parafascicle nucleus of the thalamus, anterior limb of the internal capsule, fornix, etc. The development of the stereotactic atlas and the introduction of the first stereotactic frame marked the beginning of stereotactic neurosurgery and introduced novel and improved standards in targeting and localization accuracy.

Drug-Microbiota InteractionsThe pharmacokinetics of drugs are frequently dictated not only by the host per se but also by the microorganisms present in the gastrointestinal tract. The gut microbiome can affect drug metabolism. Recent literature data shows that drugs can affect the function and composition of the gut microbiome. Both microbiota-mediated alterations in drug metabolism and drug-mediated alterations in the gut microbiome can have beneficial or detrimental effects on the patient. In this workshop, we will closely look into the mechanisms driving these reciprocal drug–gut microbiota interactions so much needed to guide the development of microbiome-targeted dietary or pharmacological interventions, which may have the potential to enhance drug efficacy or reduce drug side effects. Additionally, we will focus on specific potential mechanisms underlining the drug-mediated alterations on the gut microbiome and the potential implications for psychoactive drugs.

Microbiota research methodsMicrobiome Research Methods workshop will focus on the laboratory and computational techniques needed to perform a clinical/preclinical study of the microbiome. This will include study design, experimentation procedures (laboratory techniques, gnotobiotic and axenic animal models), and lastly quantitative, qualitative, and functional analysis of the microbes.

Conference Bag Discounts

Nerva - Hypnotherapy for IBS
FREE Life Time Access
Access the Nerva through your institutional student email to gain FREE access to all Nerva content valued at 149$ annually

50% Discount of IBS Clinician's Course on Nerva - Hypnotherapy for IBSAccess the IBS Clinician's Course on Nerva by entering the promo code BRAINGUTCON after registering to Nerva with your student email

20% KENHUB DiscountBy clicking on the picture you directed to a link that allows you to claim a 20% discount on this amazing anatomy learning platform

NextBike 200 FREE Minutes Discount Download the application NextBike, register completely, and enter the promo code 2022ETM to acquire 200 FREE minutes to enjoy Zagreb

https://medizzy.com/

MEDizzy 1-month Premium Access Enter the promo code BRAINGUTAXIS after registering to access the 1-MONTH PREMIUM ACCESS to all of MEDizzy medical educational content

15% FLIX Bus discount For all travels until the 15th of December
Click on the picture and enter your credentials and the "Company name": Brain Gut Axis Conference on the link

Museum of Illusions Zagreb 20% DiscountAcquire the discount when presenting the accrediation of the conference at the entrance

Zagreb Brochures Click on the link and find new information about Zagreb and enjoy the city


Abstracts - BGA 2022

Exacerbation of migraine in a patient treated for Crohn's disease: A case report

Bodakoš Karla1, Divković Dora Rebeka2, Mirošević Zubonja Tea1,3

1 Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia
2 School of Dental Medicine, University of Zagreb, Zagreb, Croatia
3 Department of Neurology, Osijek University Hospital Centre, Osijek, Croatia

Introduction
Crohn's disease (CD) is an inflammatory bowel disease characterized by skipping lesions and transmural inflammation that can be localized in different areas of the digestive tract. Immunomodulatory therapy is used with the aim of achieving and maintaining remission of CD. With this case report, we want to present a therapeutic option that includes treatment with two monoclonal antibodies in patient suffering from both migraine and CD
Case report
We present a 48-year-old male patient who has been suffering from migraines with aura since elementary school and was diagnosed with CD at the age of 38. He also suffers from anxiety, depression, and postural tremor. The Rathke cyst was found on brain MRI, but it has no signs of activity and remains stable in size. Before diagnosis and therapy for CD, migraines were successfully treated with analgesics. After diagnosis of CD, the gastroenterologist introduced the immunomodulatory therapy infliximab, which keeps the CD in remission. However, with its administration, an exacerbation of migraine has occurred. In period of last ten years, many migraine prophylaxes were introduced but without great effect. Zolmitriptan had fewer effects in the treatment of pain. Topiramat and lamotrigin were causing many side effects and acupuncture was performed but without desirable effect. Three years ago, erenumab was introduced and showed great results as migraine prophylaxis in our patient
Discussion
Our patient has received two monoclonal antibodies simultaneously, infliximab in therapy for CD and erenumab in therapy for migraine. Consulting available literature and pharmaceutical companies, no contraindications or interactions were found when using both medications. This therapeutic option has made great significance in quality of life of our patient because migraine pain was finally managed while keeping CD in remission.

A vertical sleeve gastrectomy as the treatment of insulin resistance and hypothyroidism:
A case report

Divković Dora Rebeka1, Bodakoš Karla2, Mirošević Gorana3

1 School of Dental Medicine, University of Zagreb, Zagreb, Croatia
2 Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia
3 Clinical Hospital Center Sestre Milosrdnice, Zagreb, Croatia

Introduction
A vertical sleeve gastrectomy (VSG) is an effective treatment for clinically severe obesity since it significantly and long-lastingly affects weight loss and, therefore, improves obesity-related comorbidities. Because 90% of adults with type 2 diabetes are overweight, we present you with a case report of this diabetic surgical treatment.
Case report
A 35-year-old male patient was admitted to the Clinical Hospital Center Sestre Milosrdnice in March 2016. The patient complained of sleepiness, lethargy, impaired concentration, and a constant feeling of hunger. The examination was performed and confirmed that he had a body weight of 219 kg and positive family anamnesis for type 2 diabetes. Due to suspicion of type 2 diabetes laboratory results were made. They showed increased levels of TSH, and insulin, decreased levels of T4, and guk levels lowered after glucose loading. They also indicated the presence of anti-TPO. Adipositas, autoimmune hypothyroidism, and insulin resistance were diagnosed.The patient was prescribed Levothyroxine and Metformin, with the possibility of bariatric surgery if the weight drops below 175 kg. In September 2016, the patient body weight was 164 kg, and VSG was performed in October 2016. Six months later control laboratory findings with therapy and weight loss (106 kg) were normal. The patient had no complaints 6 months follow-up.
Discussion
Although more evidence, including long-term outcomes, is needed, laparoscopic VSG may be an effective treatment for patients with morbid obesity.

Gut microbiota analysis of a patient with post-SSRI sexual dysfunction: Case report and literature review

Karačić Andrija1, Jelić Anđela2, Kos Blaženka3

1 Gut Microbiome Center Zagreb, Croatia
2 Catholic University del Sacro Cuore, Milano, Italy
3 Faculty of Food and Biotechnology, University of Zagreb, Zagreb, Croatia

Introduction
Selective serotonin reuptake inhibitors have antibacterial activity with a detrimental effect on the gut microbiota. The resulting increase in gut permeability can lead to sexual dysfunction mediated through microglia activation and cytokine release, known as post-SSRI sexual dysfunction.
Case report
A 26-year-old male patient presented with sexual dysfunction consisting of erectile dysfunction, loss of libido, genital numbness and concomitant brain fog, anhedonia, akathisia, and insomnia. Symptoms started immediately after cessation of fluoxetine therapy and had lasted for 18 months without changes in severity prior to presentation to a multidisciplinary team consisting of a medical doctor, psychologist, and functional medicine practitioner. The patient was diagnosed with post-SSRI sexual dysfunction. A fecal microbiota analysis was conducted using 16s rRNA next-generation gene sequencing (BIOMES, Wildau, Germany). Our analysis shows low richness and diversity of the gut microbiota. The taxonomic analysis revealed a dominance of the phylum Firmicutes (82.69%) over phylum Bacteroidetes (14.26%), expressed in a high Firmicutes/Bacteroidetes ratio (=5.8). The relative proportion of phylum Proteobacteria (1.7%) was low. On the genus level, the taxonomic analysis revealed high relative abundances of saccharolytic genera Bifidobacterium (0.56%), Prevotella (10.71%), Roseburia (1.41%), and Blautia (7.84%) and low relative abundances of proteolytic genera Bacteroides (0.56%) and Bilophila (0.013%). The proportions of anti-inflammatory species Lactobacillus (0.0%), Ackermansia muciniphila (0.0%), and Faecalibacterium prausnitzii (3.36%) were low.
Discussion
The conducted analysis revealed substantial perturbances of the gut microbiota. Although it is unclear whether the fluoxetine therapy caused those, the patient’s symptoms could be associated with gut microbiota perturbances based on the literature on similar conditions. Although no causative relationship between the reported gut microbiota perturbances and symptoms of PSSD can be made, further research is necessary to investigate treatment options for PSSD based on gut microbiota profiling.

Hereditary transthyretin amyloidosis - in the context of liver transplantation

Knez Nora1, Kukić Sandro1, Kulaš Marjan1, Planinić Ivo2, Mrzljak Anna3

1 School of Medicine, University of Zagreb, Zagreb, Croatia
2 Department of Cardiovascular Diseases, University Hospital Centre Zagreb, Croatia
3 Department of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Croatia

Introduction
Hereditary transthyretin amyloidosis (hATTR) is a rare progressive autosomal-dominant disorder of protein metabolism caused by the mutated transthyretin (TTR) gene. It is a systemic disease with a variable phenotype due to the more than 100 different mutations in the TTR gene, the Val30Met variant being by far the most common. Amyloidogenic forms of TTR are insoluble aggregated fibrils, accumulated in the extracellular matrix, resulting in morphological and functional impairment. Most commonly hATTR is associated with sensorimotor peripheral neuropathy, autonomic dysfunction, and impaired cardiac function. Other organs that are often affected include the kidneys, eyes, and gastrointestinal tract. Hepatocytes synthesize 98% of TTR, and liver transplantation (LT) has been considered a treatment option.
Case report
We present a case of a 56-years-old male patient who underwent LT in July 2022. His family history was positive for hATTR; the diagnosis was confirmed in 2017 with a subcutaneous fat biopsy and genetic testing that showed Asp38Glu mutation. His past medical history revealed a heart transplant in May 2019 due to restrictive cardiomyopathy, peripheral sensorimotor neuropathy, parasympathetic autonomic dysfunction, and chronic kidney disease. LT postoperative course was unremarkable and his immunosuppression consisted of steroids, mycophenolate mofetil, and tacrolimus. His short-term follow-up is unremarkable.
Discussion
In the case of hATTR, LT is implemented as a disease-modifying therapy hoping to slow disease progression in the future. A longer follow-up is needed to demonstrate the benefit of LT. However, potential short- and long-term transplant-related complications direct a need for better treatment options.

The Concentration of Vasoactive Intestinal Peptide is altered by Dipeptidyl Peptidase IV Deficiency among the Gut-Brain Axis in Experimental Colitis

Kršek Antea1, Bedoić Edvard1, Detel Dijana2, Batičić Lara2

1 Faculty of Medicine,University of Rijeka, Rijeka, Croatia
2 Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia

Introduction
Inflammatory bowel disease (IBD) describes a chronic inflammatory disorder of the gastrointestinal tract including Crohn’s disease and ulcerative colitis. Dipeptidyl-peptidase IV (DPP IV/CD26) is a membrane-bound and soluble glycoprotein, showing a pleiotropic role in the organism. We hypothesized that DPP IV/CD26 contributes to the pathogenesis of IBD by influencing circulating and tissue levels of its substrate, vasoactive intestinal peptide (VIP), along the gut-brain axis.
Materials and methods
A 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn-like model of colitis has been induced in CD26 deficient and wild-type (C57BL/6) mice. Control animals received the same volume of 50% ethanol and saline solution. Animals were monitored daily and sacrificed 2, 7, 10, 15, and 30 days after TNBS application. Histomorphometric and pathohistological analyses of colon tissues were performed. VIP concentrations and protein expressions as well as DPP IV/CD26 enzymatic activity along the gut-brain axis have been determined at both systemic and local levels by ELISA and Western blot techniques.
Results
This study revealed that CD26 deficient mice constitutionally have higher serum VIP concentrations compared to their wild-type counterparts. VIP concentrations in serum of both mice strains reach their maximum values in the acute phase of colitis, significantly more accentuated in CD26 deficient mice. Likewise, VIP levels in the brain showed increased concentrations in both mice strains in acute inflammation with higher values in CD26 deficient mice.
Discussion
Results of this study indicate that mechanisms activated locally in the gut mucosa upon inflammatory events induce changes in neuropeptides in the brain, thereby, confirming the importance of the gut-brain axis in IBD. In addition, DPP IV/CD26 has been confirmed to play an important neuroimmunomodulatory role in IBD pathogenesis, which should further be evaluated.

Gut-brain parasitosis: multi-organ cystic echinococcosis – a case report

Kukić Sandro1, Kulaš Marjan1, Nora Knez1, Balen Topić Mirjana2,3

1 School of Medicine, University of Zagreb, Zagreb, Croatia
2 School of Medicine, University of Zagreb, Zagreb, Croatia
3University Hospital for Infectious Diseases „Dr. Fran Mihaljević“, Zagreb, Croatia

Introduction
"Human cystic echinococcosis is a worldwide cestodal zoonosis, significantly prevalent in Mediterranean countries. Infective Echinococcus granulosus egg enters the human gut via the feco-oral route, develops into a larval form, invades portal circulation, and transforms into a cyst in reached tissue. Primary cyst/s are mostly found in the liver (50-70%), lungs (20%), and rarely in the brain (1-2%) and other organs. After spontaneous/trauma-induced perforation of the fertile primary cyst, the „daughter cysts“ can seed neighbor or remote organs, and cause secondary echinococcosis.
We present a case of a 45-year-old female patient repeatedly surgically treated due to multi-organ cystic echinococcosis, recurrently involving the brain, late diagnosed with primary liver echinococcosis.
"
Case report
"From 2006 to 2014 she underwent surgical treatments of the lung, heart, and repeatedly (6x) brain, accompanied by multiple albendazole courses, due to echinococcosis. Routine follow-up MSCT of the brain (2019) detected a new cyst, located in the pterygopalatine fossa. Subsequently, MSCT of the abdomen revealed multiple cysts, permeating the left hepatic lobe, left kidney, and peritoneum.
At admission, besides from 4 cm enlarged liver, the physical examination was unremarkable. Laboratory showed an absolute eosinophilic blood count of 1,200x106/µL and elevated GGT (263 U/I). Under albendazole therapy, transnasal incision, drainage, and scolicidal instillation of the cyst were performed in a tertiary institution by a skilled otorhinolaryngologist. Molecular diagnostics from samples and serology were positive. One month later, left hemihepatectomy, left nephrectomy, ileum resection, and removal of intraabdominal cysts were performed. Until now, there were no signs of disease recurrence.
"
Discussion
Cerebral parasitoses in humans are rare, and in most of them, the point of entry is the gastrointestinal tract. As the isolated primary disease of the brain is extremely rare, in the case of brain echinococcosis, especially if recurrent, other body sites should be searched for primary lesion/s to prevent further recurrences.

Challenging case of dysphagia - bisphosphonate-induced esophageal stricture

Kulaš Marjan1, Nora Knez1, Kukić Sandro1, Bišćanin Alen2

1 School of Medicine, University of Zagreb, Zagreb, Croatia
2 Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia

Introduction
"Bisphosphonates are widely prescribed medications that are the mainstay of osteoporosis treatment. Although bisphosphonates are generally considered safe medications, upper gastrointestinal mucosal lesions represent a potential adverse effect. Long-term treatment may result in esophageal erosions followed by stricture formation.
"
Case report
"We present a case of a 58-year-old female patient that was referred to our department due to progressive dysphagia in the past year. Her past medical history included cutaneous sarcoidosis and osteoporosis. Dysphagia and suspected esophageal stenosis required additional workup. Upper endoscopy showed subtotal stenosis of the distal esophagus along with the performed biopsy. Patohistological analysis indicated high-grade dysplasia. MSCT revealed nonspecific esophageal thickening (6mm) without additional pathological findings, and the patient was referred to our tertiary center as suspected esophageal neoplasm. During hospitalization in the center, upper endoscopy and pathohistological analysis were repeated and malignancy was excluded which begged the question of esophageal stricture etiology. Medical history was thoroughly re-examined. Focus has been put on her bisphosphonate therapy due to osteoporosis. After further research, rare adverse effects of bisphosphonates therapy were noted. Bisphosphonate therapy was discontinued and proton pump inhibitors were introduced to the treatment plan. This treatment showed to be effective and successful.
"
Discussion
Esophageal stricture due to chronic mucosal injury represents an uncommon adverse effect of bisphosphonate treatment. Bisphosphonate therapy must be considered in the differential diagnosis of progressive dysphagia and esophageal stenosis in patients treated for osteoporosis.

Contribution of the gut microbiome Bacteroides thetaiotaomicron (B. theta) to Alzheimer’s disease-related traits

Nguyen Vu Thu Thuy1, König Svenja2, Steinert Florian2, Eggert Simone3, Formes Henning4, Kins Stefan2, Reinhardt Christoph3, Endres Kristina1

1 Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
2 Department of Human Biology and Human Genetics, University of Kaiserslautern, Kaiserslautern, Germany
3 Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
4 Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

Introduction
Bacteroides thetaiotaomicron (B. theta) is dominating the gut microbiome of most mammals. This strictly anaerobic gut symbiont adheres to food particles where it degrades sugars and was shown to contribute to gut maturation. It also colonizes the mucus layer of intestinal epithelial cells of the host in both, healthy and diseased conditions. An anti-inflammatory probability within the gut has been shown in preclinical models of Crohn's Disease. Moreover, decreased neuronal and vagal afferent innervation observed in germ-free mice was found to be normalized by colonialization with B. theta. Germ-free mice not only display deficits in gut innervation but also have been reported to exert lowered neuronal number and e.g. neurotransmitter levels in the brain. These effects may be conferred by the gut-brain axis via the vagus nerve or via a lack of bacterial products such as the anti-inflammatory pirin-like protein.
Materials and Methods
Here, we investigated the hallmarks of Alzheimer’s disease (AD) in the brain of germ-free mice as compared to mice mono-colonialized by B. theta. We analyzed the number of mature neurons, presynaptic density, processing of the Amyloid precursor protein, and inflammatory status within two brain regions: the hippocampus and the cerebellum.
Resuts
The hippocampus is a region highly vulnerable to pathogenesis while the cerebellum is thought to be mildly affected. Interestingly, e.g., secretion of neuroprotective APPsα decreased in hippocampus while levels increased in cerebellum as a response to the introduction of the bacterium.
Discussion
Our results hint at high region-specific reactivity towards B. theta which might make it difficult to evaluate its overall relevance for AD.

Self-destructive Behaviors Associated With Borderline Personality Disorder

Parać Ena1, Herceg Dora1, Bagarić Ante2

1 School of Medicine, University of Zagreb, Zagreb Croatia
2 Institute for Addiction, University Psychiatric Hospital Vrapče, Zagreb, Croatia

Introduction
Borderline Personality Disorder (BPD) is a psychiatric condition characterized by pronounced impulsivity and unstable interpersonal relationships and self-image. Strong, fluctuating emotions, chronic feelings of emptiness, and psychological pain that BPD patients experience can result in self-damaging behaviors, such as self-mutilation, addiction, and suicide attempts.
Case report
A 45-year-old female patient is receiving ongoing management in the outpatient clinic for borderline personality disorder (BPD) and substance use disorder (SUD). The patient first presented to the hospital in 2013 following an attempted suicide using benzodiazepines and alcohol. Upon admission, she reported depressive symptoms and feelings of emptiness, hopelessness, and meaninglessness. An excessive tendency to alcohol consumption and pervasive suicidal thoughts were present. She had suffered from traumatic experiences in her early life. She stated she subsequently suffered from untreated anorexia. She reports feeling ”as if she was programmed to act in an excessive way” and that she ”cannot be self-consistent”. She has been hospitalized several times throughout the years with recurring suicidal ideations and intoxication with alcohol and drugs. When the patient’s stability was ensured, psychological and pharmacological treatments were regularly introduced to manage her addiction to multiple psychoactive substances and BPD. Her current medication plan includes an antidepressant (escitalopram), an anxiolytic (diazepam), a sedative-hypnotic (zolpidem), and an antipsychotic (quetiapine). Intensive psychodynamic therapy (individual and group) and different forms of sociotherapy have been provided. She is currently attending group sessions in the outpatient clinic that take place three times a week. In the last follow-up, the patient showed no signs of auto- and hetero-aggression, denied suicidal thoughts, and is motivated to continue treatment
and stay abstinent.
Discussion
The unstable mood and impulsivity of BPD patients make them more susceptible to auto-destructiveness. Since they struggle to mitigate negative emotions, a comorbid SUD is highly prevalent in BPD patients. Dependence-producing substances contribute to an exacerbation of BPD symptomatology, and as such, complicate the treatment even further. Although alcoholism, drug addiction, suicide attempts, repetitive self-harm, and an unfavorable early environment generally serve as poor prognostic factors in patients diagnosed with BPD; continuous and committed treatment in the form of dialectic and cognitive behavioral therapy may give remarkable results, especially when aided by psychoeducation and
pharmacotherapy.

Comparison of effects of Fetal Bovine Serum and bFGF on cell number, Map2 expression and apoptotic cell death in murine neural stem cells

Petrović Dražen Juraj1, Hribljan Valentina1,Jagečić Denis1, Mitrečić Dinko1

1 Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia

Introduction
Standardization of cultivation and differentiation of stem cells is one of the prerequisites needed for the successful utilization of stem cell technology. With a wish to improve the features of neural stem cells originating from mouse embryos, we explored the effects of 1% Fetal Bovine Serum (FBS) and 0,2% basic Fibroblast Growth Factor on the number of cells (by counting cell nuclei), differentiation towards neurons (by measuring expression of Microtubule Associated Protein 2 (Map2) and apoptotic cell death (by measuring Cleaved Caspase 3 (CCasp3).
Materials and Methods
Neural stem cells isolated from 14 days old mouse embryos were dissociated and plated on Poly-D-Lysine and Laminin coated coverslips and exposed to 1% FBS and 0.2% bFGF. After performing immunocytochemistry, images were obtained on a confocal microscope and analyzed by Imaris and R studio.
Resuts
Cell number analysis revealed the highest cell number in the bFGF group. Analysis of the Map2 marker for neuronal differentiation and CCasp3 marker for apoptosis showed the highest expression in the Control group. The FBS-treated group revealed markedly bigger and flat cell morphology.
Discussion
Analysis revealed that bFGF increased cell number, while it decreased expression of Map2, stressing its strong proliferative and anti-differentiation effect. On the other hand, FBS did not influence cell number or survival, but it caused the flattening of cells and of their nuclei, which might indicate differentiation towards astrocytes. The highest expression of Map2 and CCasp3 was found in a control group, suggesting that differentiation towards neurons was accompanied by increased cell death.

Brain lateralization in bilinguals - functional transcranial color doppler against functional magnetic resonance imaging

Redžepi Saleha1, Holzmann Jana2

1 Faculty of Medicine University of Sarajevo, Sarajevo, Bosnia and Hercegovina
2 Neurological Practice Dr. Holzmann, Kaufbeuren, Germany

Introduction
Bilingualism is the ability to use two or more languages with equal or near equal fluency. How the brain, often seamlessly, selects, controls, and switches between languages is still being investigated. In this research, it was used word generation task, which is a well-validated and commonly used productive language task, to test whether language lateralization is equivalent for first (L1) and second languages (L2) in bilinguals. A secondary aim was to consider whether there is any impact of age of acquisition (AoA).
Materials and Methods
24 participants were included in the study (18 female, 6 male; mean age 23 y.o.). Participants were highly proficient bilinguals, all with English as a second language, who were working or studying in Oxford, UK at an advanced level. Each participant was tested in English (L2) and their native language (L1; French or German). Each trial started with an
auditory tone and the written instruction “Clear Mind” (5 s), followed by the letter cue to which the participant silently generated words (15 s), and then overt word generation (5 s). To restore baseline activity, participants were instructed to relax (25 s) at the end of each trial
Resuts
Common activations between native and foreign languages at TP0 included the bilateral supplementary motor area. Then, at TP1 conjunctions were observed also in the bilateral early visual and insular cortex, the left inferior frontal gyrus, the left inferior temporal gyrus, the left precentral gyrus, and in subcortical structures including the left pallidum and the thalamus. Again, a similar pattern was observed at TP3.
Discussion
Based on the results of this study, there is no difference in lateralization strength for L1 and L2 in those who acquired a foreign language early compared to those who acquired a foreign language later.

Can we dismiss neurosyphilis in the differential diagnosis of early-onset dementia?

Vuksan-Ćusa Zrinka1, Knez Nora1, Vuksan-Ćusa Bjanka1,2

1 School of Medicine University of Zagreb, Zagreb, Croatia
2 Department of Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, Zagreb, Croatia

Introduction
Neurosyphilis represents the central nervous system sequelae of syphilis, an infection caused by Treponema pallidum. It develops years after an unrecognized primary infection and is often misdiagnosed due to the broad range of clinical manifestations. Psychiatric manifestations are often underestimated in differential diagnoses.
Case report
We present a case of a 46-year-old married male patient with a history of seizures and graduate cognitive decline over the past three years. He was treated with different antiepileptic drugs without significant improvement. His clinical presentation included diverse symptomatology, such as confusion, anxiety, delirium, hallucinations, headaches, psychomotor retardation, and incoherent speech, which obtained further detailed diagnostic studies. Brain MRI showed cortical atrophy in the right hemisphere, predominantly in the temporal-parietal region. Standard laboratory tests were without abnormalities. Cerebrospinal fluid (CSF) analysis revealed lymphocytosis and increased protein levels. Additionally, due to the suspected neurosyphilis, reactive VDRL, TPHA, and IgG-FTA-ABS were indicated and the diagnosis of neurosyphilis was confirmed. He was treated with crystalline penicillin for a month. Despite laboratory results improvement, cognitive deficits, such as dysfunction of the visual-spatial working memory, executive functions, operational and verbal memory, learning, attention processes, and perception remained unchanged. His Mini-Mental State Examination (MMSE) score was 18 out of 30.
Discussion
The indolent course and the variety of clinical presentations make the syphilis diagnosis complex. Misdiagnosis may result in fatal neurosyphilis development which can be confused with other neuropsychiatric conditions. This case report emphasizes the importance of considering neurosyphilis in the differential diagnosis of patients with early-onset dementia.

Eosinophilic colitis: A study of a rare and treatable gastroenterological case

Watarkar Sakshi 1, Mastrorocco Elisabetta 1, Pugliese Nicola1, Masetti Chiara1, Spaggiari Chiara1, Aghemo Alessio1

1 Faculty of Biomedical Sciences, Humanitas University, Rozzano, Italy
2

Introduction
Eosinophilic colitis (EC) is a rare heterogeneous disease under the category of primary eosinophilic gastrointestinal diseases, showing a bimodal peak of distribution. The etiopathology is usually unknown. The diagnosis is mainly done by histopathological studies, proving an excess of eosinophils infiltrating the colon. However, standardized diagnosis guidelines have not been established. In this article, we describe the case of a female Caucasian in her mid-30s, diagnosed with eosinophilic colitis, who presented with ascites, abdominal pain, and nausea. Histopathological studies manifested eosinophils in the colonic lamina propria. Systemic causes of eosinophilic colitis were excluded. The patient was eventually treated with corticosteroids, proton pump inhibitors, and systemic antacids, and further kept on a regular follow-up to check for any alterations.
Case report
A young Caucasian female presented with abdominal pain and swelling. A previous history of severe ascetic fluid accumulation without nausea or vomiting was noted. Past medical history also showed epigastralgia, PCOD, fetal suffering, anal fissure, and a polypectomy. On physical examination, the abdomen was noted to be distended and globose, with bulging flanks, and the presence of shifting dullness upon palpation. Blood analysis showed leukocytosis with marked eosinophilia (WBCs 13700/mmc, 28% eosinophils). There was a significant abdominal effusion in all quadrants evident on CT. Subsequently, an evacuative paracentesis was performed, and 4000cc ascetic fluid was drained. The ascetic fluid showed marked eosinophilia (82% eosinophils). Systemic causes of eosinophilia were excluded through bone marrow biopsy and hematological studies. Biopsy samples taken during colonoscopy showed eosinophilic granulocytes infiltrating the colonic lamina propria.
Discussion
The patient presented with abdominal pain and ascites. Further tests revealed peripheral eosinophilia and colon thickening. Based on the clinical manifestations and biopsy images, eosinophilic ascites and eosinophilic colitis were diagnosed. The patient was treated with corticosteroids, proton pump inhibitors, and systemic antacids. The etiology of the diagnosis was unknown.