Aggregatibacter actinomycetemcomitans: From the Oral Cavity to the Heart Valves.

Aggregatibacter actinomycetemcomitans (A. actinomycetecomitans) is a Gram-negative bacterial species that is an essential component of the oral microbiota. Due to its aggregative properties, it plays a role in the pathogenesis of human diseases. The presence of the surface proteins Fim, Briae, and microvesicles enables the bacterium to adhere to the epithelial surface and the tooth's surface. The presence of leukotoxin A (LtxA), which plays an important role in the pathogenicity of the bacterium, has been associated with both periodontitis and the etiology of rheumatoid arthritis (RA). A. actinomycetecomitans is also associated with several other systemic diseases and complications, such as endocarditis and different abscesses. In addition to leukotoxin A, A. actinomycetecomitans possesses several different virulence factors, including bacteriocins, chemotaxis inhibitory factors, cytotoxic factors, Fc-binding proteins, immunosuppressive factors, lipopolysaccharide collagenase, fibroblast inhibitory factors, antibiotic resistance determinants, adhesins, invasive factors and factors that inhibit the function of polymorphonuclear leukocytes. The ability of A. actinomycetemcomitans lipopolysaccharide to induce macrophages to secrete the interleukins IL-1, IL-1ß, and tumor necrosis factor (TNF) is of considerable importance. The primary etiologic factor in the pathogenesis of periodontal disease is the oral biofilm colonized by anaerobic bacteria. Among these, A. actinomycetemcomitans occupies an important place as a facultative anaerobic bacterium. In addition, A. actinomycetemcomitans possesses many virulence factors that contribute to its potential to cause cancer. This article provides an overview of the virulence factors of A. actinomycetecomitans and its association with various systemic diseases, its oncogenic potential, and the treatment options for infections caused by A. actinomycetecomitans.

A Putative Role of Candida albicans in Promoting Cancer Development: A Current State of Evidence and Proposed Mechanisms.

Candida albicans is a commensal fungal species that commonly colonizes the human body, but it is also a pervasive opportunistic pathogen in patients with malignant diseases. A growing body of evidence suggests that this fungus is not only coincidental in oncology patients, but may also play an active role in the development of cancer. More specifically, several studies have investigated the potential association between C. albicans and various types of cancer, including oral, esophageal, and colorectal cancer, with a possible role of this species in skin cancer as well. The proposed mechanisms include the production of carcinogenic metabolites, modulation of the immune response, changes in cell morphology, microbiome alterations, biofilm production, the activation of oncogenic signaling pathways, and the induction of chronic inflammation. These mechanisms may act together or independently to promote cancer development. Although more research is needed to fully grasp the potential role of C. albicans in carcinogenesis, the available evidence suggests that this species may be an active contributor and underscores the importance of considering the impact of the human microbiome on cancer pathogenesis. In this narrative review, we aimed to summarize the current state of evidence and offer some insights into proposed mechanisms.

Impact of Immediate and Delayed Breast Reconstruction on Quality of Life of Breast Cancer Patients.

A mastectomy affects the psychological, social, and sexual well-being of patients. Research has confirmed that breast reconstruction is important for improving the quality of life in patients with breast cancer. The aim of this study was to assess the quality of life of patients who underwent a mastectomy followed by immediate or delayed breast reconstruction. This prospective study was conducted from January 2018 to March 2020 at the Clinical Hospital Center Osijek, using the health questionnaire SF-36. The study included 79 patients. The results of the study showed that patients who underwent a mastectomy had the lowest scores in the domain of restriction due to physical difficulties, 18.8 (6.3−31.3), in physical functioning and limitation due to emotional difficulties, 16.7 (8.3−33.3), in mental health. In immediate breast reconstruction, patients rated better physical health (p < 0.001), while patients who underwent delayed breast reconstruction rated their mental health worse (p < 0.001) as measured by the SF-36 questionnaire. Conclusion: The results of this study show that patients without breast reconstruction rated their quality of life worse than patients who underwent immediate and delayed breast reconstruction after mastectomy. There is no difference in the quality of life between patients who underwent immediate and delayed breast reconstruction after mastectomy.

The Association between Drinking Water Quality and Inflammatory Bowel Disease-A Study in Eastern Croatia.

The incidence rate of inflammatory bowel disease (IBD) is becoming a global health problem that could be caused by changes in environmental and lifestyle habits. The study aimed to identify the association between the quality of drinking water, i.e., physiochemical and biological aspects of the phenotype and activity of IBD in Eastern Croatia. The study included 312 patients (63.4% ulcerative colitis, UC, and 36.6% Crohn's disease, CD) from the area of Eastern Croatia. The data were collected by questionnaires and the analysis of the water safety, based on 65 samples of drinking water by the patient's water supply method (public supply, rural water supply, and private well). IBD was active in 38.0% patients (34.0% CD and 40.0% UC). Significant differences (p = 0.001) were observed in the distribution of patients, according to counties in which they lived in. The largest deviation was noted in coliform bacteria, Escherichia coli, and enterococci bacteria, Fe, Al, and nitrate in rural water supply and private wells, although, without significant impact on IBD phenotype and activity. The hazard quotient (HQ) simulations showed that children are a sensitive group, regarding exposure to nitrates in drinking water over a long period of time, so there is a need for further monitoring and analysis of this issue.

IMPORTANCE OF ZINC CONCENTRATION IN SEMINAL FLUID OF MEN DIAGNOSED WITH INFERTILITY.

The prevalence and importance of male infertility make it a serious worldwide medical and social problem. The aim of this study was to determine if there were any significant differences in zinc concentrations in seminal fluid in men diagnosed with infertility compared to control group, and if there were, to determine how it affected the number and percentage of sperm cells with normal motility and morphology. A case-control study was conducted in the Osijek-Baranja County from January 2014 to June of 2015. The study included 276 subjects referred to biochemistry laboratory of the Osijek University Hospital Centre, 100 (36.2%) of them with low sperm count confirmed by spermiogram after 3 months. Semen samples were processed according to the World Health Organization criteria, and zinc concentrations were determined using spectrophotometry and direct colorimetry without deproteinization on a chemistry analyzer (Olympus AU 680, Beckman Coulter, Tokyo, Japan). Study results showed the men with low sperm count to be significantly older (Mann Whitney U test: p=0.013) and to have lower zinc levels (χ2-test: p<0.001). Further analysis included 100 (36.2%) patients with low sperm count. In the group of infertile men, those with low sperm count had higher zinc levels compared to men with azoospermia (Mann Whitney U test: p=0.036), suggesting a connection between lower zinc level in seminal fluid and male fertility. Zinc as a biological marker and an antioxidant affects sperm count, motility and morphology. Zinc supplemental therapy could improve seminal parameters in patients diagnosed with low sperm count. Dietary habits of the subjects differ regionally, and future research could make a solid foundation for complementary approach to treatment of male infertility.

Positive Effect of Breastfeeding on Child Development, Anxiety, and Postpartum Depression.

BACKGROUND: Postpartum depression is a psychiatric disorder that starts from the second to the sixth week after birth. Breastfeeding is considered a protective factor for postpartum mood swings. This paper aims to examine the effect of breastfeeding on postpartum depression and anxiety, and how it affects child development. METHODS: The study included 209 pregnant women, 197 puerperea, and 160 women at the end of the third month after delivery, followed through three time-points. The instruments used in the study were the Edinburgh Postpartum Depression Scale (EPDS), Beck's Depression Inventory (BDI), and Beck's Anxiety Inventory (BAI). RESULTS: Postpartum mothers with low risk of PPD breastfed their children more often than mothers with a mild or severe risk of perinatal depression. Mean values on the BDI scale three months after giving birth were higher in mothers who did not breastfeed their child (M = 3.53) than those who did breastfeed their child (M = 2.28). Postpartum anxiety measured by BAI was statistically negatively correlated (rs-, 430) with the duration of breastfeeding. CONCLUSION: Nonbreastfeeding mothers are more depressed and anxious compared to breastfeeding mothers.

Assessment of the Quality of Life in Patients before and after Coronary Artery Bypass Grafting (CABG): A Prospective Study.

The aim of this study was to examine the quality of life and to report on the utility and QALY measures in patients before and after coronary artery bypass grafting (CABG); to investigate whether the SF-12 is comparable with the SF-36 for measuring health-related quality of life of patients with CABG; and to determine the impact of individual predictors on poor quality of life assessment after rehabilitation. This prospective study was conducted between January 2017 and December 2018 at the University Hospital Center Osijek, at three time points: pre-operation, 1 month after surgery, and after rehabilitation. The study was conducted with the SF-36 and SF-12 health questionnaires on 47 participants. After rehabilitation, there was a significant improvement in all domains of quality of life. The highest score was given to the change in pain (BP); mean scores were 63.8 (95% CI 56.9 to 70.6) (p = 0.001). The lowest grade (the lowest quality) after rehabilitation was in the domain of limitations due to physical difficulties (RP); arithmetic mean was 48.5 (95% CI 41 to 55.9) (p < 0.001). Quality-adjusted life-year was 0.41 (95% CI 0.38-0.44) after the CABG. The results of this study show that patients with coronary heart disease have poor quality of life before surgery. One month after the surgery, the quality of life improved, but was still inadequate. One year after surgery, satisfactory results were obtained in almost all subscales. The SF-36, SF-12, and its components, can be used effectively in patients with CABG. Age, gender, lifestyle, and risk factors in our sample of participants are not predictors of poor quality of life assessment after rehabilitation.

THE EFFECT OF DAILY PHYSICAL ACTIVITY ON THE ACTIVITY OF INFLAMMATORY BOWEL DISEASES IN THERAPY-FREE PATIENTS.

It has been suggested that various environmental factors play a very important role in the etiology of inflammatory bowel diseases (IBDs) and that they have a significant effect on the course of these diseases. The aim of this study was to investigate the effect of daily physical activity on the activity of IBDs in therapy-free patients. This cross-sectional population based study was conducted in eastern Croatia from January to June 2016. The study included 312 patients, mean age 49.9±15.0 years, 53.2% of males and 46.8% of females; there were 63.4% of ulcerative colitis (UC) and 36.6% of Crohn's disease (CD) patients. Sociodemographic characteristics of patients, data on their daily physical activity and type of therapy taken were collected through a specifically designed and validated questionnaire, while the activity of UC and CD was evaluated using the Mayo index and Harvey-Bradshaw index. The study showed that 24.0% of patients were not taking therapy. Daily physical activity was connected to IBD in study patients when taking both diseases collectively (Fisher exact test; p<0.001), as well as to the inactivity of CD (Fisher exact test; p=0.001) and UC (Fisher exact test; p=0.006), when observing each disease separately. Daily physical activity was connected to the inactivity of IBDs in patients not taking therapy. It is necessary to educate all IBD patients about the importance of physical activity in order to control their disease.

The investigation of hereditary and acquired thrombophilia risk factors in the development of complications in pregnancy in Croatian women.

OBJECTIVES: To investigate the genetic and acquired thrombophilic risk factors in pregnancy-associated complications and venous thromboembolism (VTE) and evaluate the association between particular thrombophilic risk factors and thromboembolic complications. METHODS: In this study, pregnant women with pregnancy complications and VTE (N = 101) were the study group, and the control group were women with normal pregnancy (N = 102). All women underwent testing for factor V Leiden mutation (FVL), mutation of the coagulation factors II (FII20210), methylenetetrahydrofolate reductase (MTHFR), plasminogen activator inhibitor-1, antithrombin III (ATIII), protein C (PC) and protein S, lupus anticoagulant (LAC) antibodies, anticardiolipin antibodies and anti-beta-2-glycoprotein-1. RESULTS: In this study group, mutations of the FVL was 15.8% (16/101), FII20210 5.9% (6/101) and the MTHFR at locus 677 was TT in 19.8% (20/101). Deficiency of ATIII and PC were rare: 3.0% and 1.0%, respectively. LAC were significantly higher in the study group than in the control group: 32.7% versus 3.9%; p < 0.0005. Pregnant women with VTE have been more frequent for FVL (41.7%; p < 0.005), PC deficiency (25.0%; p < 0.005) and LAC (33.3%; p < 0.005). Combination of FVL and MTHFR mutation was related to the risk of recurrent fetal death and habitual abortion. CONCLUSION: The inherited and the acquired thrombophilic risk factors were found to be up to 10 times more common in the study group than in the control group.

VKORC1 gene polymorphisms and adverse events in Croatian patients on warfarin therapy.

OBJECTIVE: The objective was to determine the impact of VKORC1 polymorphisms on warfarin anticoagulant therapy (stable warfarin maintenance dose, time required to reach therapeutic dose and time spent in therapeutic range) and its adverse events (overanticoagulation and bleeding events, time to first overanticoagulation or bleeding event, and therapy for bleeding events) in Croatian patients. MATERIALS: Blood samples were collected from 186 patients on stable warfarin therapy. METHODS: VKORC1 1173C>T and VKORC1 –1639G>A gene polymorphisms were analyzed using real-time PCR. Prothrombin time international normalized ratio (INR) values were determined and overanticoagulation as well as bleeding events were recorded. RESULTS: Both tested VKORC1 gene polymorphisms (VKORC1 1173C>T and VKORC1 -1639G>A) were in perfect linkage disequilibrium. Genotype analysis showed that 33.9% of patients were homozygous for wild-type, 46.8% were heterozygous and 19.4% were homozygous for the variant allele. We have found a statistically significant difference between variantallele carriers and wild-type patients in stable warfarin maintenance dose (p<0.001) and incidence of bleeding events (p=0.040). Patients homozygous for variant-allele were more likely to experience an overanticoagulation event in the first 30 days of therapy (p=0.040). CONCLUSIONS: Our study showed that VKORC1 1173C>T and VKORC1 -1639G>A gene polymorphisms are associated with stable warfarin maintenance dose and adverse events of warfarin therapy.

Management of cervical ectopic pregnancy after unsuccesful methotrexate treatment.

BACKGROUND: Cervical pregnancy is rare and dangerous form of ectopic pregnancy which can be treated surgically or conservatively. Methotrexate is reasonable conservative option with high efficiency and acceptable level of side effects. Aim of this paper is to present possible treatment option in case of methotrexate failure, still keeping the postulates of minimal invasive surgery. CASE: We describe a case of cervical ectopic pregnancy in nulliparous female that was unsuccessfully treated with single dose, local, ultrasound guided intraamniotic methotrexate. Due to vaginal bleeding caused by remaining products of conception a hysteroscopic resection was performed. CONCLUSION: Despite the problems that can occur in methotrexate treatment, it is still by far, cheapest and most effective treatment of cervical pregnancies. If necessary, procedure can be combined with other minimal invasive surgical procedures leading to satisfactory results. Hysteroscopic resection has enabled us to remove the product of conception from cervix making the minimal damage to the local tissue, thus preserving fertility.

Cervical cancer in Osijek-Baranja County--possibilities for prevention.

In Osijek-Baranja County, there was a rise in the number of non-invasive and fall of invasive cervical cancer in the period 2000-2008, but cervical cancer still represents an important public health problem in Osijek-Baranja County. Cervical cancer in 2008 was the ninth female cancer site and represents 3.5% of all malignant diseases in women. In the same year it was also at the ninth place of all cancer deaths in women with a share of 3.3%. The large number of women cervical cancer was detected at an advanced stage of the disease so that there is an pincrease in mortality from cervical cancer. Although the incidence of cervical cancer is lower in relation to Croatia and other countries in the region, the mortality rate is still higher than in the countries of Western Europe. In order to reduce the incidence and mortality of cervical cancer primary task of the public health system is the introduction of secondary prevention through properly organized screening program. The program should be tailored to the financial and human resources and local specificities, with the agreement on a strategy that will give the best results.

Tumor-cell-targeted methionine-enkephalin analogues containing unnatural amino acids: design, synthesis, and in vitro antitumor activity.

A series of new peptides (8-25) containing different unnatural amino acids of the adamantane type (1-6), was synthesized. Possible cytotoxic activity on human cervical adenocarcinoma (HeLa), larynx carcinoma (HEp-2), colon carcinomas (HT-29, Caco-2), poorly differentiated cells from lymph node metastasis of colon carcinoma (SW-620), mammary gland adenocarcinoma (MCF-7), and melanoma (HBL) cells were tested by the MTT assay. The results were compared with the effect of methionine-enkephalin (Tyr-Gly-Gly-Phe-Met, or opioid growth factor, OGF), and its shorter N-terminal fragments. Peptide analogues containing C(alpha alpha)-dialkylated glycine (Aaa1, 1) or C(alpha)-alkylated glycine (Aaa2, 2) amino acid residues showed antitumor activity against melanoma, larynx carcinoma, colon carcinomas, and colon metastasis cell lines in vitro. The pentapeptide Tyr-(R,S)-Aaa2-Gly-Phe-Met (18) was the most effective analogue especially against the most antitumor drug-resistant cell lines HEp-2 and SW-620. Apoptosis as a mode of cell death was confirmed in these tumor cells after exposure to pentapeptide 18.