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Klara Cervena,1,2 Anna Siskova,1,2 Jiri Jungwirth,3,4 Marin Volari&cacute;,5 Jan Kral,6 Pavel Kohout,7 Miroslav Levy,8 Veronika Vymetalkova1,2,9 1Institute of Experimental Medicine, Czech Academy of Sciences, Prague, 142 00, Czech Republic; 2Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, 128 00, Czech Republic; 3Institute of Physiology, 1st Faculty of Medicine Charles University, Prague, 121 08, Czech Republic; 4Department of Surgery, Weiden Clinic, Weiden in der Oberpfalz, 92637, Germany; 5Laboratory for Non-Coding DNA, Ru&dstrok;er Boškovi&cacute; Institute, Zagreb, 10000, Croatia; 6Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, 140 21, Czech Republic; 7Department of Internal Medicine, 3rd Faculty of Medicine Charles University and Faculty Thomayer Hospital Prague, Prague, 140 00, Czech Republic; 8Department of Surgery, First Faculty of Medicine, Charles University and Thomayer Hospital Prague, Prague, 140 59, Czech Republic; 9Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, 323 00, Czech RepublicCorrespondence: Klara Cervena, Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, Prague, 142 00, Czech Republic, Email klara.cervena@iem.cas.czIntroduction: The development of colorectal cancer (CRC) is a multistep process accompanied by the accumulation of mutations that start from specific precancerous lesion – colorectal adenomas (CA). CRC incidence and mortality can be reduced by the early identification of these neoplasm. Colonoscopy is the most widely used screening method for CRC identification. Nowadays, clinical research interest is shifting to the use of liquid biopsy that may help with the early diagnosis of CA and CRC. In our previous study, we identified long non-coding RNA MALAT1 gene amplification associated with the development of CA.Methods: This study aimed to describe the potential of MALAT1 expression levels in the adenoma tissue of patients used in the previous study by real-time qPCR. Furthermore, we analysed the plasma samples of an independent group of patients with CA (n=97), CRC (n=101), and cancer-free individuals (CFI, n=48).Results: There was no difference in the MALAT1 expression level between CA patients with or without MALAT1 amplification. However, the plasma MALAT1 expression levels were significantly upregulated in patients with CRC and CA compared to CFI (for both p< 0.001). Moreover, a correlation between MALAT1 expression and histological types of adenomas was identified– high-CRC-risk adenomas also displayed the highest MALAT1 expression levels. Furthermore, in CRC patients, MALAT1 levels were associated with a response to therapy.Conclusion: MALAT1 expression levels could serve as a promising circulating biomarker for early CA and CRC diagnosis, and even as a predictor of therapy response in CRC patients.Keywords: MALAT1, colorectal adenomas, colorectal cancer, plasma, liquid biopsy

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To date, over 40 epigenetic and 300 epitranscriptomic modifications have been identified. However, current short-read sequencing-based experimental methods can detect <10% of these modifications. Integrating long-read sequencing technologies with advanced computational approaches, including statistical analysis and machine learning, offers a promising new frontier to address this challenge. While supervised machine learning methods have achieved some success, their usefulness is restricted to a limited number of well-characterized modifications. Here, we introduce Modena, an innovative unsupervised learning approach utilizing long-read nanopore sequencing capable of detecting a broad range of modifications. Modena outperformed other methods in five out of six benchmark datasets, in some cases by a wide margin, while being equally competitive with the second best method on one dataset. Uniquely, Modena also demonstrates consistent accuracy on a DNA dataset, distinguishing it from other approaches. A key feature of Modena is its use of 'dynamic thresholding', an approach based on 1D score-clustering. This methodology differs substantially from the traditional statistics-based 'hard-thresholds.' We show that this approach is not limited to Modena but has broader applicability. Specifically, when combined with two existing algorithms, 'dynamic thresholding' significantly enhances their performance, resulting in up to a threefold improvement in F1-scores., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The role of chronic stress in the development of chronic diseases, especially multimorbidity, through the pathways of increasing allostatic load, and finally, allostatic overload (the state when a compensatory mechanism is likely to fail) is being emphasized. However, allostatic load is a dynamic measure that changes depending on sex, gender, age, level and type of stress, experience of a stressful situation, and coping behaviors. Many other factors such as race, ethnicity, working environment, lifestyle, and circadian rhythm of sleep are also important. The aim of this paper was to synthesize the available information on allostatic load differences, especially those connected to sex/gender and age, and to provide a model for the future study of allostatic load, with a focus on these differences. By carefully studying allostatic load factors, we realized that many studies do not take this allostatic load difference into account in the analysis methods. In this paper, we also support the idea of further research to develop new allostatic load analysis strategies that will include all knowledge about sex/gender differences and that will, in more detail, explain numerous changeable social and educational factors that are currently accepted as biological ones. Furthermore, specific allostatic load biomarkers are expressed differently in different age groups, indicating that the discrepancies cannot be attributed solely to sex/gender disparities. This kind of approach can be valuable, not only for better explaining the differences in the frequency and age of onset of chronic diseases and multimorbidity, but also for the potential planning and development of preventive actions based on the aforementioned sex/gender and age disaparities, in order to prevent the most frequent diseases and to establish specific biomarker cut-off values for each sex/gender and age group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Volarić, Šojat, Volarić, Včev, Keškić and Majnarić.)

Satellite DNAs (satDNAs) are tandemly repeated sequences that make up a significant portion of almost all eukaryotic genomes. Although satDNAs have been shown to play an important role in genome organization and evolution, they are relatively poorly analyzed, even in model organisms. One of the main reasons for the current lack of in-depth studies on satDNAs is their underrepresentation in genome assemblies. Due to complexity, abundance, and highly repetitive nature of satDNAs, their analysis is challenging, requiring efficient tools that ensure accurate annotation and comprehensive genome-wide analysis. We present a novel pipeline, named satellite DNA Exploration (SatXplor), designed to robustly characterize satDNA elements and analyze their arrays and flanking regions. SatXplor is benchmarked against other tools and curated satDNA datasets from diverse species, including mice and humans, showcase its versatility across genomes with varying complexities and satDNA profiles. Component algorithms excel in the identification of tandemly repeated sequences and, for the first time, enable evaluation of satDNA variation and array annotation with the addition of information about surrounding genomic landscape. SatXplor is an innovative pipeline for satDNA analysis that can be paired with any tool used for satDNA detection, offering insights into the structural characteristics, array determination, and genomic context of satDNA elements. By integrating various computational techniques, from sequence analysis and homology investigation to advanced clustering and graph-based methods, it provides a versatile and comprehensive approach to explore the complexity of satDNA organization and understand the underlying mechanisms and evolutionary aspects. It is open-source and freely accessible at https://github.com/mvolar/SatXplor., (© The Author(s) 2024. Published by Oxford University Press.)

Eukaryotic genomes are replete with satellite DNAs (satDNAs), large stretches of tandemly repeated sequences that are mostly underrepresented in genome assemblies. Here we combined nanopore long-read sequencing with a reference-guided assembly approach to generate an improved, high-quality genome assembly, TcasONT, of the model beetle Tribolium castaneum Enriched by 45 Mb in repetitive regions, the new assembly comprises almost the entire genome sequence. We use the enhanced assembly to conduct global and in-depth analyses of abundant euchromatic satDNAs. Unexpectedly, we show the extensive spread of satDNAs in gene-rich regions, including long arrays. The sequence similarity relationships between satDNA monomers and arrays indicate a recent exchange of satDNA arrays between different chromosomes. We propose a scenario of their genome dynamics characterized by repeated bursts of satDNAs spreading through euchromatin, followed by a process of elongation and homogenization of arrays. We find that suppressed recombination on the X Chromosome has no significant effect on the spread of satDNAs but the X rather tolerates the amplification of satDNAs into longer arrays. Analyses of arrays' neighboring regions show a tendency of one satDNA to be associated with transposable-like elements. Using 2D electrophoresis followed by Southern blotting, we prove Cast satDNAs' presence in the fraction of extrachromosomal circular DNA (eccDNA). We point to two mechanisms that enable this satDNA spread to occur: transposition by transposable elements and insertion mediated by eccDNA. The presence of such a large proportion of satDNA in gene-rich regions inevitably gives rise to speculation about their possible influence on gene expression., (© 2024 Volarić et al.; Published by Cold Spring Harbor Laboratory Press.)

Less than 2% of all symptomatic multiple myeloma (MM) has immunoglobulin D (IgD) as monoclonal protein. Biclonal gammopathy is much rarer. At the time of diagnosis, disease is often in advanced stage, including renal failure, anemia, hypercalcemia and lytic bone lesions. Due to the rarity of myeloma itself, but also due to the fact that anti-IgD antisera is not used in routine practice, there are only a few reports of IgD MM described in the literature. This case report describes a patient with IgD lambda MM with anemia and renal failure. Anemia, renal failure, and > 80 percent plasma cells in bone biopsy in our patient with IgD lambda MM meets International Myeloma Working Group criteria for diagnosis of MM. The patient clinical course was similar to other patients with IgD MM. The final result of serum protein immunofixation (s-IFE) showed IgD lambda and free lambda monoclonal bands. To prevent misdiagnosis, it is necessary to use anti-IgD and anti-IgE antisera whenever the serum protein immunofixation with IgA, IgM, IgG, kappa and lambda antiserums shows a kappa or lambda monoclonal band without monoclonal band in heavy chain., Competing Interests: Potential conflict of interest None declared., (Copyright Croatian Society of Medical Biochemistry and Laboratory Medicine.)

5S ribosomal DNAs (rDNAs) are arranged in tandem and are often under-represented in genome assemblies. In the present study, we performed a global and in-depth analysis of the 5S rDNAs in the model insect Tribolium castaneum and its closely related species Tribolium freemani . To accomplish this goal, we used our recently published genome assemblies based on Nanopore and PacBio long-read sequencing. Although these closely related species share the 5S rRNA gene sequence with high homology, they show a different organization of the 5S rDNA locus. Analysis of 5S rDNA arrays in T. castaneum revealed a typical tandemly repeated organization characterized by repeat units consisting of the 121 bp long 5S rRNA gene and the 71 bp long nontranscribed spacer (NTS). In contrast, T. freemani showed a much more complex organization of 5S rDNA arrays characterized by two patterns. The first is based on the association of 5S rRNA gene with arrays of a satellite DNA, representing the NTS sequence of the 5S rDNA genes in T. freemani . The second, more complex type is characterized by a somewhat less frequent occurrence of the 5S rRNA gene and its association with longer satellite DNA arrays that are regularly interrupted by Jockey-like retrotransposons. This organization, in which the ribosomal gene is associated with two completely different repetitive elements such as satellite DNAs and retrotransposons, suggests that the 5S rRNA gene, regardless of its crucial function in the genome, could be a subject of extremely dynamic genomic rearrangements.

Introduction: Due to treatment of end-stage-renal-disease (ESRD), continuous peritoneal dialysis (CAPD) is used in 11% of cases and is associated with several PD-associated infections., Methods: Clinical data on 71 patients with CAPD were evaluated in addition to exit site infections and episodes of acute peritonitis (AP)., Results: There were 39 men and 32 women. Average age was 61 years when we began CAPD and average time spent on CAPD program was 3.35 years. Illness that dominantly caused ESRD was diabetes (23 patients). Exit site infection was mostly caused by S epidermidis-MRSE and AP was most commonly caused by Staphylococcus sp. group. Most common cause of death was cardiovascular disease. At the end of this study, 9 patients were alive and still on CAPD, 10 were transplanted, 15 switched to HD and 36 died., Conclusion: Optimal prevention measures and treatment of infectious complications in CAPD is necessary for better treatment possibilities., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

The spectrum, intensity, and overlap of symptoms between functional gastrointestinal disorders (FGIDs) and other gastrointestinal disorders characterize patients with FGIDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis of FGID and the applicability of a given treatment is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found to cause the continuous existence of a low level of inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and the intestinal functions, including the involvement of gut bacteria. In this review paper, we intend to promote the hypothesis that FGIDs should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic, and microbiome pathways. This hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, that is omnipresent in chronic health conditions. A better understanding of inflammation's role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs may reduce patient heterogeneity and help clarify the pathophysiology of this disease to allow for better treatment.

Functional dyspepsia is a common functional disorder of the gastrointestinal tract that is responsible for many primary care visits. No organic changes have been found to explain its symptoms. We hypothesize that modern lifestyles and environmental factors, especially psychological stress, play a crucial role in the high prevalence of functional dyspepsia and metabolic syndrome. While gastrointestinal tract diseases are rarely linked to metabolic disorders, chronic stress, obesity-related metabolic syndrome, chronic inflammation, intestinal dysbiosis, and functional dyspepsia have significant pathophysiological associations. Functional dyspepsia, often associated with anxiety and chronic psychological stress, can activate the neuroendocrine stress axis and immune system, leading to unhealthy habits that contribute to obesity. Additionally, intestinal dysbiosis, which is commonly present in functional dyspepsia, can exacerbate systemic inflammation and obesity, further promoting metabolic syndrome-related disorders. It is worth noting that the reverse is also true: obesity-related metabolic syndrome can worsen functional dyspepsia and its associated symptoms by triggering systemic inflammation and intestinal dysbiosis, as well as negative emotions (depression) through the brain-gut axis. To understand the pathophysiology and deliver an effective treatment strategy for these two difficult-to-cure disorders, which are challenging for both caregivers and patients, a psychosocial paradigm is essential.

Background: Aging is associated with many personal, social, and environmental challenges that increase the risk of loneliness. Loneliness is a painful emotional experience associated with a perceived lack of connection and intimacy. Loneliness accelerates health deterioration, but the presence of chronic health conditions (comorbidities) in older individuals may potentiate the feeling of loneliness. The relationships between health status and loneliness in older individuals have not been assessed in an integrated manner, although it is necessary for planning efficient interventions. The aim of this study was to fill in this knowledge gap, by attempting to create an integrated model of loneliness in older individuals., Methods: The sample consisted of 189 (58% F) older individuals (> 60 years) (mean ± SD, 78.47 ± 6.65), attendees in Primary Health Care. Different factors associated with loneliness in the older population were assessed, and classified as demographic, environmental, physical (health-related), and psychological, in addition to functional abilities. A set of standard questionnaires was used to assess psychological factors and functional abilities. The hierarchical regression model assessed the effect of particular blocks of factors on status loneliness. The second aim was to analyze how psychological factors mediate associations between health status (comorbidity level) and loneliness., Results: Indicated that increasing comorbidity, anxiety, lack of positive moods, not having hobbies/activities, low perception of social support, impaired cognitive function, and suppression of emotion expression, are significant predictors of loneliness. Mediation analysis informed us of how to help patients with comorbidities feel less lonely. Interventions that were suggested were those that can reduce anxiety and depression, improve cognitive abilities and emotional regulation control, and enhance social support., Conclusions: Results can help understand the pathophysiology loops linking poor health status (comorbidity level) of older individuals and loneliness, and have significant potentials from the translational perspectives, as a decision-support tool., (© 2023. The Author(s).)

The red flour beetle Tribolium castaneum is an important pest of stored agricultural products and the first beetle whose genome was sequenced. So far, one high-copy-number and ten moderate-copy-number satellite DNAs (satDNAs) have been described in the assembled part of its genome. In this work, we aimed to catalog the entire collection of T. castaneum satDNAs. We resequenced the genome using Illumina technology and predicted potential satDNAs via graph-based sequence clustering. In this way, we discovered 46 novel satDNAs that occupied a total of 2.1% of the genome and were, therefore, considered low-copy-number satellites. Their repeat units, preferentially 140-180 bp and 300-340 bp long, showed a high A + T composition ranging from 59.2 to 80.1%. In the current assembly, we annotated the majority of the low-copy-number satDNAs on one or a few chromosomes, discovering mainly transposable elements in their vicinity. The current assembly also revealed that many of the in silico predicted satDNAs were organized into short arrays not much longer than five consecutive repeats, and some of them also had numerous repeat units scattered throughout the genome. Although 20% of the unassembled genome sequence masked the genuine state, the predominance of scattered repeats for some low-copy satDNAs raises the question of whether these are essentially interspersed repeats that occur in tandem only sporadically, with the potential to be satDNA "seeds".

Background: Personality traits as alexithymia and type D personality may impair health related quality of life (HRQoL) in patients with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Aim of this study was to evaluate personality traits in patients with IBS and IBD and their impact on HRQoL., Materials and Methods: The subjects (40 patients with IBS, 40 with IBD and 40 health control subjects) completed SF-36 questionnaire, TAS-20 and DS14 scale., Results: Patients with IBS and IBD had higher results on TAS-20 and DS14 scale when compared with healthy controls. Also IBS patients had higher scores than IBD patients. Higher scores on TAS-20 and DS14 scales in IBS and IBD patients correlate with lower HRQoL. HRQoL was poorer in IBS and IBD patients than in healthy control subjects., Conclusions: Alexithymia and type D personality in IBS and IBD patients are associated with lower HRQoL and psychological interventions should be considered.

Background: Physical frailty and cognitive decline are two major consequences of aging and are often in older individuals, especially in those with multimorbidity. These two disorders are known to usually coexist with each other, increasing the risk of each disorder for poor health outcomes. Mental health disorders, anxiety and depression, are common in older people with multimorbidity, in particular those with functional or sensory deficits, and frailty., Purpose: The aim of this study was to show how physical frailty, cognitive impairments and mental disorders, cluster in the real life setting of older primary care (PC) patients, and how these clusters relate to age, comorbidities, stressful events, and coping strategies. Knowing that, could improve risk stratification of older individuals and guide the action plans., Methods: Participants were older individuals (≥60, N = 263), attenders of PC, independent of care of others, and not suffering from dementia. For screening participants on physical frailty, cognitive impairment, and mental disorders, we used Fried's phenotype model, the Mini-Mental State Examination (MMSE), the Geriatric Anxiety Scale (GAS), and the Geriatric Depression Scale (GDS). For testing participants on coping styles, we used the 14-scale Brief-Coping with Problems Experienced (Brief-COPE) questionnaire. To identify clusters, we used the algorithm fuzzy k-means . To further describe the clusters, we examined differences in age, gender, number of chronic diseases and medications prescribed, some diagnoses of chronic diseases, the number of life events, body mass index, renal function, expressed as the glomerular filtration rate, and coping styles., Results: The most appropriate cluster solution was the one with three clusters, that were termed as: functional (FUN; N = 139), with predominant frailty or dysfunctional (DFUN; N = 81), and with predominant cognitive impairments or cognitively impaired (COG-IMP; N = 43). Participants in two pathologic clusters, DFUN and COG-IMP, were in average older and had more somatic diseases, compared to participants in cluster FUN. Significant differences between the clusters were found in diagnoses of osteoporosis, osteoarthritis, anxiety/depression, cerebrovascular disease, and periphery artery disease. Participants in cluster FUN expressed mostly positive reframing coping style. Participants in two pathological clusters were represented with negative coping strategies. Religion and self-blame were coping mechanisms specific only for cluster DFUN; self-distraction only for cluster COG-IMP; and these two latter clusters shared the mechanisms of behavioral disengagement and denial., Conclusion: The research approach presented in this study may help PC providers in risk stratification of older individuals and in getting insights into behavioral and coping strategies of patients with similar comorbidity patterns and functional disorders, which may guide them in preparing prevention and care plans. By providing some insights into the common mechanisms and pathways of clustering frailty, cognitive impairments and mental disorders, this research approach is useful for creating new hypotheses and in accelerating geriatric research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wittlinger, Bekić, Guljaš, Periša, Volarić and Trtica Majnarić.)

The flour beetle Tribolium freemani is a sibling species of the model organism and important pest Tribolium castaneum . The two species are so closely related that they can produce hybrid progeny, but the genetic basis of their differences has not been revealed. In this work, we sequenced the T. freemani genome by applying PacBio HiFi technology. Using the well-assembled T. castaneum genome as a reference, we assembled 262 Mb of the T. freemani genomic sequence and anchored it in 10 linkage groups corresponding to nine autosomes and sex chromosome X. The assembly showed 99.8% completeness of conserved insect genes, indicating a high-quality reference genome. Comparison with the T. castaneum assembly revealed that the main differences in genomic sequence between the two sibling species come from repetitive DNA, including interspersed and tandem repeats. In this work, we also provided the complete assembled mitochondrial genome of T. freemani . Although the genome assembly needs to be ameliorated in tandemly repeated regions, the first version of the T. freemani reference genome and the complete mitogenome presented here represent useful resources for comparative evolutionary studies of related species and for further basic and applied research on different biological aspects of economically important pests.

The term resilience, which has been present in science for almost half a century, stands for the capacity of some system needed to overcome an amount of disturbance from the environment in order to avoid a change to another stable state. In medicine, the concept of resilience means the ability to deal with daily stress and disturbance to our homeostasis with the intention of protecting it from disturbance. With aging, the organism becomes more sensitive to environmental impacts and more susceptible to changes. Mental disturbances and a decline in psychological resilience in older people are potentiated with many social and environmental factors along with a subjective perception of decreasing health. Distinct from findings in younger age groups, mental and physical medical conditions in older people are closely associated with each other, sharing common mechanisms and potentiating each other's development. Increased inflammation and oxidative stress have been recognized as the main driving mechanisms in the development of aging diseases. This paper aims to reveal, through a translational approach, physiological and molecular mechanisms of emotional distress and low psychological resilience in older individuals as driving mechanisms for the accelerated development of chronic aging diseases, and to systematize the available information sources on strategies for mitigation of low resilience in order to prevent chronic diseases.

The long-read Nanopore sequencing has been recently applied for assembly of complex genomes and analysis of linear genome organization. The most critical factor for successful long-read sequencing is extraction of high molecular weight (HMW) DNA of sufficient purity and quantity. The challenges associated with input DNA quality are further amplified when working with extremely small insects with hard exoskeletons. Here, we optimized the isolation of HMW DNA from the model beetle Tribolium and tested for use in Nanopore sequencing. We succeeded in overcoming all the difficulties in HMW handling and library preparation that were encountered when using published protocols and commercial kits. Isolation of nuclei and subsequent purification of DNA on an anion-exchange chromatography column resulted in genomic HMW DNA that was efficiently relaxed, of optimal quality and in sufficient quantity for Nanopore MinION sequencing. DNA shearing increased average N50 read values up to 26 kb and allowed us to use a single flow cell in multiple library loads for a total output of more than 13 Gb. Although our focus was on T. castaneum and closely related species, we expect that this protocol, with appropriate modifications, could be extended to other insects, particularly beetles.

Management of hair loss in women presents several challenges for general practitioners, who are the first in identifying its cause and consequences in everyday clinical practice. It is usually associated with multiple secondary factors, including endocrine disorders, drug side effects, and physical or emotional stress. We report a possible pathophysiological link between hyperprolactinemia and alopecia in a patient with preexisting autoimmune thyroid disease, which has not been documented in a significant number in the literature. A 27-year-old female patient with a previous history of an autoimmune thyroid disease on hormone substitution therapy presented to a family doctor with signs of frontal alopecia that had started several months previously. On examination, frontal alopecia was confirmed. Laboratory results and thyroid ultrasound confirmed autoimmune thyroid disease, with reduced parathyroid hormone and elevated prolactin. Her female sex hormones were in the normal range. Due to elevated prolactin levels, computed tomography of the pituitary gland was performed, which excluded any brain pathology. Based on available data, there is no published systematic analysis on hyperprolactinemia-induced alopecia in previous autoimmune diseases (large cohort studies). This report indicates that, due to moderately elevated prolactin values, consideration of alternative causes and further diagnostics are necessary to exclude a prolactin-producing tumor of the pituitary gland.

Background: To explore corellation of anxiety, depression ant type of personality in inflammatory bowel disease (IBD) and compare with peptic ulcer (PU)., Subjects and Methods: In this study, prevalence of anxiety, depression and type of personality was investigated in 362 cases divided into three groups: 112 of IBD patients, 122 of peptic ulcer patients and 128 of control group who didn't have any gastrointestinal or psychic complaints. IBD and peptic ulcer diagnosis were established by standard diagnostic procedures (anamnesis, clinical manifestations, laboratory, endoscopy and biopsy in IBD and upper endoscopy in peptic ulcer). Anxiety and depression were established by Hamilton anxiety rating scale (HAM-A) and Hamilton rating test for depression (HAM-D). Type of A/B personality was established by Bortner scale and D type of personality by Denollet scale (DS14)., Results: Anxiety was found in 47 (41.9%) and depression in 44 (38.3%) of a total of 112 IBD cases. In group with peptic ulcer anxiety was found in 40 (32.8%) and depression aalso in 40 (32.8%) of total 122 cases. In control group anxiety was diagnosed in 21 (16.4%) and depression in 20 (15.6%) of total 128 cases. Anxiety and depresson were significantly higher in both groups than in control group but anxiety and depression were significantly higher in IBD group than peptic ulcer group. D type of personality was statistically significant in peptic ulcer group., Conclusion: Anxiety and depression in IBD and peptic ulcer cases have a greater prevalence compared to the normal population and surprisingly are higher in IBD than peptic ulcer group. D type of personality is associated with peptic ulcer.

Background: Nutritional status is an important factor for predicting the risk of developing complications after a surgical procedure. Many nutritional assessments are used in clinical practice, but their role in predicting postoperative outcomes is unknown. Therefore, the aim of this study was to assess the utility of nutritional risk factors at the diagnosis of colorectal cancer (CRC) for predicting early postsurgical complications., Methods: This was a prospective observational study including 127 patients with CRC at diagnosis. Their preoperative nutritional status was analyzed by body mass index (BMI), triceps and subscapular skinfolds and two nutritional scales: the Patient-Generated Subjective Global Assessment (PG-SGA) and the Malnutrition Universal Screening Tool (MUST). The outcome variables, including postoperative complications, length of hospital stay and mortality, were analyzed., Results: Patients identified as malnourished by PG-SGA score had prolonged hospital stays (p = 0.01). The risk of infection was increased in older patients (hazard ratio, HR 1.12; 95% confidence interval, CI 1.04-1.21) but was not associated with nutritional status. Early wound dehiscence was increased in patients with higher BMI (HR 1.15; 95% CI 1.01-1.29), with higher subscapular skinfold thickness and increased age (HR 1.05; 95% CI 1.05-1.10). Postoperative mortality was not significantly associated with nutritional status., Conclusion: Malnourished patients, as identified by the PG-SGA score, stayed longer in hospital than patients who were not malnourished, while increased BMI was recognized as a risk factor for wound dehiscence.

Background: The seasonality of acute myocardial infarction and progressive heart failure has been well established so far. Cardiac troponins (cTns) are organ-specific, not disease-specific, biomarkers. The seasonality of cTns has not been reported before., Methods: Data were collected from the emergency admission unit of a community hospital in eastern Croatia for each month of the year 2014 covering the number of patients whose doctors requested high-sensitivity cTn I (hs-cTn I) testing, the number of positive test results and hospital admissions., Results: The proportion of patients with positive test results was 15.75% (350 patients out of 2221 patients referred to testing), with the males being outnumbered by the females (F: 57.15%, M: 42.85%) ( p = 0.069). The month with the highest number of patients with positive test results was December, whereas the month with the lowest number of those patients was January ( p < 0.001). The highest numbers of patients referred to testing (30.9%) and of those with positive test results (50.8%) were found in the oldest age group (76+)., Conclusion: Tracking the results of cTns testing during patient admissions to emergency departments would be a more effective approach from a public health perspective than tracking the number of patients diagnosed with a particular cardiovascular (CV) disease and could be used as a research approach to guide a search for precipitating factors for CV disease specific to a local community.

Background: To explore correlation between clinical and endoscopic indices in inflammatory bowel disease (IBD) patients., Subjects and Methods: There were 112 patients with inflammatory bowel disease. All patients with diagnosed IBD was established a degree of clinical and endoscopic disease activity. CDAI (Crohn's disease activity index) was used as clinical and SES-CD (Simplified Endoscopic Crohn Disease Index) as endoscopic index for Crohn's disease. For ulcerative colitis Truelov & Witts index was used as clinical and Baron as endoscopic activity index. Correlation of clinical and endoscopic indices were compared in Crohn disease (CD) and ulcerative colitis (UC). Patients were analyzed by clinical entities - CD and UC, according to sex, age, parameters of anemia, duration of disease and education., Results: In the total of 112 IBD patients there were 69 patients diagnosed as ulcerative colitis (61.6%) and 43 as Crohn's disease (38.4%). There were 58 (51.8%) women and 54 (48.2%) men. Comparison between endoscopic and clinical indices in CD and UC demonstrated no significant differences in ilnness activity. Endoscopic and clinical disease activity was associated with a higher inflammatory parameters (CRP and leucocytes, L) and lower parameters of hemoglobin (Hb) and MCV., Conclusion: Our research has established a good correlation between clinical and endoscopic index of disease activity in the CB and UC in inflammation. Clinical indices can be used for monitoring inflammation.

Aim: To explore the prevalence of amebiasis in inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis, in patients in Clinical hospital Mostar (Bosnia and Herzegovina, region of Herzegovina)., Methods: In this study, Entamoeba histolytica/dispar prevalence was investigated in fresh faeces by native microscopy and immunochromatographic rapid assay "RIDA(®)QUICK Entamoeba test", in 119 cases of new found IBD patients, 84 of ulcerative colitis and 35 of Crohn's disease and in control group who had also 119 patients who didn't have any gastrointestinal complaints. IBD diagnosis was established by standard diagnostic procedures (anamnesis, clinical manifestations, laboratory, endoscopy and biopsy)., Results: Entamoeba histolytica/dispar were found in 19 (16.0 %) of a total of 119 cases, 12 (14.3 %) of the 84 patients with ulcerative colitis and 7 (20.0 %) of the 35 patients with Crohn's disease. As for the 119 patients in the control group who had not any gastrointestinal complaints, 2 (1.7 %) patients were found to have E. histolytica/dispar in their faeces. Amoeba prevalence in the patient group was determined to be significantly higher in group with Crohn's disease, ulcerative colitis and IBD total than in the control group (p < 0.001)., Conclusion: Ameba infections in patients with Crohn's disease and ulcerative colitis, have a greater prevalence compared to the normal population.

Aim: The main goal of this study was to compare the biochemical and histopathological findings in patients with sustained virological response (SVR) before and two years after the therapy with pegylated interferon α-2a and ribavirin in chronic hepatitis C., Subjects and Methods: The study was conducted at the Department of Internal Medicine and the Clinic for Infectious Diseases of the Clinical Hospital Mostar. The study included 48 patients whose treatment for chronic hepatitis C with pegylated interferon α-2a and ribavirin was finished two years prior to the achieved SVR at the end of the treatment. The main criterion for inclusion was a negative result of HCV RNA, determined by the RealTime HCV assay. After taking a history, physical examination, laboratory tests: AST, ALT, GGT, a liver biopsy were performed with the help of the ultrasound. The assessment of necroinflamatory score was determined by histologic activity index (HAI) score, and the stage of fibrosis according to Knodell's numerical score., Results: The values of AST and ALT levels were statistically significantly decreased after the successful treatment (p<0.001), as well as the value of HAI score (p=0.001) and the stage of fibrosis (p=0.010), in contrast to GGT (p=0.054). For the components of HAI score like focal necrosis (0.001) and portal inflammation (0.042) the result showed that they were significantly higher before the therapy, which was not true for the piecemeal (p=0.054) and confluated necrosis (p=0.078). The improvement of HAI score after therapy was found in 36 patients (75.0%), and 27 patients (56.2%) showed an improvement in the degree of fibrosis with the most common improvement of 1 degree (85.7%). One third of patients (31.3%) had the same result in the degree of fibrosis before and after the therapy. Before the treatment, a positive correlation was observed between ALT (p=0.039) and AST (p=0.04) with HAI, AST and the stage of fibrosis (p=0.04). In contrast, after the treatment the only correlation was observed between AST and the stage of fibrosis (p=0.042)., Conclusion: Virological and biochemical responses in patients with SVR may not reflect the histopathological effects of the treatment and therefore these patients should be monitored for the possible development of the liver cirrhosis and hepatocellular carcinoma.

We assessed the diagnostic efficacy of plasma Myeloperoxidasis (MPO) alone or in combination with cardiac troponin I (cTnI) for detecting ACS in patients presenting with chest pain initiating within 24 h before the hospital admission. In this prospective cohort study were included all respondents who have visited outpatient clinic of internal diseases, University Hospital Mostar because of chest pain and suspected acute coronary syndrome within 24 h of the onset of the period of 6 months and the total sample consisted of 114 patients. Troponin and myeloperoxidase were significantly positively correlated at the beginning of treatment, myeloperoxidase was significantly positively associated with adverse cardiovascular events during hospitalization and myocardial infarction (p < 0.05), with the regression analysis did not show a significant predictor in the development of myocardial infarction (p > 0.05). Sensitivity of myeloperoxidase as a valid test detection of myocardial infarction at baseline was 0.15 and specificity was 0.85, suggesting good diagnostic value usable in the clinical practice.

To evaluate the therapeutic potential of the newly developed proton pump inhibitor lansoprazole in patients with reflux esophagitis (grade I and II according to Savary Müller criteria), the authors performed a single blind, randomized clinical trial comparing 20 mg omeprazole and 30 mg lansoprazole, involving 60 patients at two clinical hospitals. The treatment period was or 8 weeks, and main efficacy variables were healing of endoscopic changes and relief of reflux symptoms. No significant difference in terms of healing and relief of reflux symptoms was found either after 4 or after 8 weeks of treatment. In conclusion, 30 mg lansoprazole daily was found to be safe and effective therapy comparable to omeprazole in the short-term treatment for reflux esophagitis (grade I and II).