Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 ...and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.
Extracellular matrix (ECM) homeostasis is highly affected in active inflammatory bowel disease (IBD). The aim of the study was to investigate serological biomarkers of type III, IV, and V collagen ...degradation and formation, and their association with disease activity in IBD. ECM remodeling serum biomarkers were measured in 162 IBD patients, 110 with Crohn’s disease (CD) and 52 with ulcerative colitis (UC), and in 29 healthy donors. Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M) and formation (PRO-C4), and type V collagen formation (PRO-C5) were measured using ELISA. Inflammatory activity was assessed using endoscopic, clinical, and biochemical activity indices. The highest diagnostic value was identified in discriminating endoscopically moderate to severe disease in CD (PRO-C3, C3M/PRO-C3, and C4M with AUC of 0.70, 0.73, and 0.69, respectively) and UC (C3M, C3M/PRO-C3, and C4M with AUC of 0.86, 0.80, and 0.76, respectively). C4M and C3M/PRO-C3 in combination yielded AUC of 0.93 (0.66–0.90) in CD and 0.94 (0.65–0.99) in UC. This study confirmed that ECM remodeling reflected disease activity in CD and UC. A combination of C4M, C3M, and PRO-C3 biomarkers may potentially be considered as a biomarker differentiating moderate to severe endoscopic disease.
This case presents Primary Squamous Cell Carcinoma of The Endometrium with cytological and immunocytological characteristics in specimens from endometrial aspirate, Pap smear and peritoneal washing. ...Initial TVUS and clinical examination showed no abnormalities, and the first curettage sample was interpreted as benign while the second was histopathologically inconclusive. The final histopathology diagnosis in the hysterectomy specimen confirmed the diagnosis of this rare tumour.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disorder commonly diagnosed in later disease stages when it prominently manifests as malnutrition. We report on a female ...patient diagnosed with MNGIE at the age of 36. She was severely malnourished due to loss of resorptive surface after several surgical procedures, gastrointestinal dysmotility, and small intestinal bacterial overgrowth. Therefore, early and aggressive total parenteral nutrition was introduced. Although no reports have shown that nutritional support can modify the clinical outcome, this case suggests that adequate nutritional support, particularly parenteral nutrition, supervised by an experienced nutritional team, may prolong the lifespan of patients with MNGIE.
Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to ...assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn's disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers' association with endoscopic and clinical disease activity using ELISA. Patients were evaluated based on the SES-CD and CDAI for CD patients and modified MES and partial Mayo for UC patients. ELP-3 and ELM-12 were elevated in patients with IBD. Discerning CD patients in endoscopic remission and mild from moderate to severe, ELP-3 provided an AUC of 0.69 and ELM-12 an AUC of 0.73. The ELP-3 biomarker was associated with UC patients and provided the highest diagnostic power of 0.87 for remission vs. active clinical disease. The data suggest an association of ELP-3 with active CD and ELM-12 with endoscopic remission in CD patients. Additionally, ELP-3 could identify UC patients with active clinical disease from patients in remission. The noninvasive biomarkers ELP-3 and ELM-12 could be potential surrogate biomarkers of elastin degradation and endoscopic and clinical disease markers.
Double Roman domination (DRD) is a combinatorial optimization problem posed on undirected graphs. It can be interpreted as allocating certain service providers (e.g., military formations, fire ...brigades or ambulances) to chosen locations within a certain area. Thereby the whole service (i.e., response to enemy attacks, fire or medical urgencies) should be established in a least expensive way, while still assuring a required “double Roman” level of availability and redundancy of providers. The standard version of DRD treated in the literature identifies the total expense of service with the total number of needed providers. In this paper a new “minimum-cost” version of DRD is considered, which is more general and more realistic than the standard version. It takes into account the fact that the actual expenses of providing service can differ from one location to another. Thus, formally speaking, each vertex in our graph is given a cost that is intepreted as the cost of keeping one service provider at the corresponding location. First, it is noted that the considered minimum-cost DRD problem is NP-hard, not only for general graphs but also for many special graph classes. Next, a dynamic programming algorithm is constructed, which shows that the problem can still be solved in linear time if the involved graph is a tree. Finally, as a solution for general graphs, a heuristic is proposed based on greedy construction and local search. Performance of both algorithms is evaluated by experiments.
Ulcerative colitis (UC) is a multifactorial disease of unknown precise etiology and immunopathogenesis. Peripheral blood granulocytes and monocytes/macrophages are the major sources of cytokines, ...which regulate inflammation. Leukocytapheresis (LCAP) is a method where blood is processed by apheresis system that removes lymphocytes and plasma before being returned to the body. We report the first case in Croatia where we used LCAP in the treatment of a patient with severe steroid-dependent UC. After 12 LCAP procedures, good clinical response was obtained and there were no significant adverse side effects noticed. The patient remained in clinical remission over two years in which he underwent regular follow ups at outpatient clinic. Over a 10-year follow-up period after LCAP, the patient had only occasional clinical symptoms of disease activity. The clinical course was complicated with the development of metastatic colorectal carcinoma, which points to the importance of regular disease monitoring rather than the increased risk of malignant disease after LCAP. Patients with UC are a demanding group of patients that warrant the search for novel treatment strategies other than conventional pharmacological therapies. Although LCAP is still not a common treatment modality in our daily practice, data from recent studies suggest it to be an effective and safe procedure in the management of active UC patients.
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, characterized by its accumulation in tissues which results in hepatic, neurological, and/or psychiatric symptoms. The aim ...of this study was to investigate the genetics of WD in Croatian patients.
Correlation of the clinical presentation subtype and the age at onset of the diagnosis of WD with the ATP7B genotype was investigated in a group of Croatian WD patients. DNA from peripheral blood samples was tested for the p.His1069Gln by direct mutational analysis and other polymorphisms were identified by sequence analysis of coding and flanking intronic regions of ATP7B gene.
In the group of 75 WD patients of Croatian origin, 18 different mutations in ATP7B gene were detected, three of which were novel. The p.His1069Gln mutation was most frequent, being detected in 44 Croatian WD patients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15.
Clinical diagnosis of WD was confirmed in 59 patients by detecting mutations on both ATP7B alleles. The age at onset of WD and the type of WD clinical presentation showed no significant correlation with the ATP7B genotype.
The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD ...(Crohn's disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease.
Let $ G $ be a graph with the vertex set $ V(G) $. A set $ D\subseteq V(G) $ is a total k-dominating set if every vertex $ v\in V(G) $ has at least $ k $ neighbours in $ D $. The total k-domination ...number $ \gamma_{kt}(G) $ is the cardinality of the smallest total k-dominating set. For $ k = 2 $ the total 2-dominating set is called double total dominating set. In this paper we determine the upper and lower bounds and some exact values for double total domination number on pyrene network $ PY(n) $, $ n\geq 1 $ and hexabenzocoronene $ XC(n) $ $ n\geq 2 $, where pyrene network and hexabenzocoronene are composed of congruent hexagons.
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