Changes in Time to Initial Physician Contact and Cancer Stage Distribution during the COVID-19 Pandemic in Patients with Head and Neck Squamous Cell Carcinoma at a Large Hungarian Cancer Center.

The aim of our study was to compare the characteristics and time to initial physician contact in patients with head and neck squamous cell carcinoma (HNSCC) before and during the COVID-19 pandemic at a large Hungarian cancer center. This was a retrospective study of patients 18 years or older presenting at the regional cancer center of Pécs Clinical Center with HNSCC between 1 January 2017, and 15 March 2020 (the pre-COVID-19 period) and between 16 March 2020, and 13 May 2021 (the COVID-19 period). Demographic and clinical data were collected, and the time between initial symptom onset and initial physician contact (TTP) was determined. Descriptive and exploratory statistical analyses were performed. On average, the number of patients diagnosed with HNSCC per month during the pandemic decreased by 12.4% compared with the pre-COVID-19 period. There was a significant increase in stage I and stage II cancers (from 15.9% to 20.3% and from 12.2% to 13.8%, respectively; p < 0.001); a decrease in stage III and IVa,c cancers; and a significant increase in stage IVb cancers (from 6% to 19.9%; p < 0.001) during the pandemic. The median TTP increased during the pandemic from 43 to 61 days (p = 0.032). To our knowledge, this is the first study investigating the effect of COVID-19 on patients with HNSCC in the Central-Eastern European region. We found a bidirectional shift in cancer stages and increased TTP during the pandemic. Our findings highlight the necessity for more nuanced analyses of the effects of COVID-19.

Dominant suppressor genes of p53-induced apoptosis in Drosophila melanogaster.

One of the major functions of programmed cell death (apoptosis) is the removal of cells that suffered oncogenic mutations, thereby preventing cancerous transformation. By making use of a Double-Headed-EP (DEP) transposon, a P element derivative made in our laboratory, we made an insertional mutagenesis screen in Drosophila melanogaster to identify genes that, when overexpressed, suppress the p53-activated apoptosis. The DEP element has Gal4-activatable, outward-directed UAS promoters at both ends, which can be deleted separately in vivo. In the DEP insertion mutants, we used the GMR-Gal4 driver to induce transcription from both UAS promoters and tested the suppression effect on the apoptotic rough eye phenotype generated by an activated UAS-p53 transgene. By DEP insertions, 7 genes were identified, which suppressed the p53-induced apoptosis. In 4 mutants, the suppression effect resulted from single genes activated by 1 UAS promoter (Pka-R2, Rga, crol, and Spt5). In the other 3 (Orct2, Polr2M, and stg), deleting either UAS promoter eliminated the suppression effect. In qPCR experiments, we found that the genes in the vicinity of the DEP insertion also showed an elevated expression level. This suggested an additive effect of the nearby genes on suppressing apoptosis. In the eukaryotic genomes, there are coexpressed gene clusters. Three of the DEP insertion mutants are included, and 2 are in close vicinity of separate coexpressed gene clusters. This raises the possibility that the activity of some of the genes in these clusters may help the suppression of the apoptotic cell death.

Predictive factors of basic palliative and hospice care among patients with cancer visiting the emergency department in a Hungarian tertiary care center.

Introduction: Patients with advanced cancer tend to utilize the services of the health care system, particularly emergency departments (EDs), more often, however EDs aren't necessarily the most ideal environments for providing care to these patients. The objective of our study was to analyze the clinical and demographic characteristics of advanced patients with cancer receiving basic palliative care (BPC) or hospice care (HC), and to identify predictive factors of BPC and HC prior to their visit to the ED, in a large tertiary care center in Hungary. Methods: A retrospective, detailed analysis of patients receiving only BPC or HC, out of 1512 patients with cancer visiting the ED in 2018, was carried out. Sociodemographic and clinical data were collected via automated and manual chart review. Patients were followed up to determine length of survival. Descriptive and exploratory statistical analyses were performed. Results: Hospital admission, multiple (≥4x) ED visits, and respiratory cancer were independent risk factors for receiving only BPC (OR: 3.10, CI: 1.90-5.04; OR: 2.97, CI: 1.50-5.84; OR: 1.82, CI: 1.03-3.22, respectively), or HC (OR: 2.15, CI: 1.26-3.67; OR: 4.94, CI: 2.51-9.71; OR: 2.07, CI: 1.10-3.91). Visiting the ED only once was found to be a negative predictive factor for BPC (OR: 0.28, CI: 0.18-0.45) and HC (OR: 0.18, 0.10-0.31) among patients with cancer visiting the ED. Conclusions: Our study is the first from this European region to provide information regarding the characteristics of patients with cancer receiving BPC and HC who visited the ED, as well as to identify possible predictive factors of receiving BPC and HC. Our study may have relevant implications for health care planning strategies in practice.

Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia.

MiRNAs in Lung Adenocarcinoma: Role, Diagnosis, Prognosis, and Therapy.

Lung cancer has emerged as a significant public health challenge and remains the leading cause of cancer-related mortality worldwide. Among various types of lung malignancies, lung adenocarcinoma (LUAD) stands as the most prevalent form. MicroRNAs (miRNAs) play a crucial role in gene regulation, and their involvement in cancer has been extensively explored. While several reviews have been published on miRNAs and lung cancer, there remains a gap in the review regarding miRNAs specifically in LUAD. In this review, we not only highlight the potential diagnostic, prognostic, and therapeutic implications of miRNAs in LUAD, but also present an inclusive overview of the extensive research conducted on miRNAs in this particular context.

Genomic Epidemiology and Evolution of Fowl Adenovirus 1.

Fowl adenovirus 1 (FAdV-1) is the main cause of gizzard erosion in chickens. Whole genome sequencing and sequence analyses of 32 FAdV-1 strains from a global collection provided evidence that multiple recombination events have occurred along the entire genome. In gene-wise phylogenies, only the adenoviral pol gene formed a tree topology that corresponded to whole genome-based phylogeny. Virus genetic features that were clearly connected to gizzard erosion were not identified in our analyses. However, some genome variants tended to be more frequently identified from birds with gizzard erosion and strains isolated from healthy birds or birds with non-specific pathologies tended to form common clusters in multiple gene phylogenies. Our data show that the genetic diversity is greater, and the evolutionary mechanisms are more complex within FAdV-1 than previously thought. The implications of these findings for viral pathogenesis and epidemiology await further investigation.

Retrospective study of cancer patients' predictive factors of care in a large, Hungarian tertiary care centre.

OBJECTIVES: To identify predictive factors of multiple emergency department (ED) visits, hospitalisation and potentially preventable ED visits made by patients with cancer in a Hungarian tertiary care centre. DESIGN: Observational, retrospective study. SETTING: A large, public tertiary hospital, in Somogy County, Hungary, with a level 3 emergency and trauma centre and a dedicated cancer centre. PARTICIPANTS: Patients above 18 years with a cancer diagnosis (International Classification of Diseases, 10th Revision codes of C0000-C9670) who visited the ED in 2018, who had received their diagnosis of cancer within 5 years of their first ED visit in 2018 or received their diagnosis of cancer latest within the study year. Cases diagnosed with cancer at the ED (new cancer diagnosis-related ED visits) were also included, constituting 7.9% of visits. PRIMARY OUTCOME MEASURES: Demographic and clinical characteristics were collected and the predictors of multiple (≥2) ED visits within the study year, admission to inpatient care following the ED visit (hospitalisation), potentially preventable ED visits and death within 36 months were determined. RESULTS: 2383 ED visits made by 1512 patients with cancer were registered. Predictive factors of multiple (≥2) ED visits were residing in a nursing home (OR 3.09, 95% CI 1.88 to 5.07) and prior hospice care (OR 1.87, 95% CI 1.05 to 3.31). Predictive factors for hospitalisation following an ED visit included a new cancer diagnosis-related visit (OR 1.86, 95% CI 1.30 to 2.66) and complaint of dyspnoea (OR 1.61, 95% CI 1.22 to 2.12). CONCLUSIONS: Being a resident of a nursing home and receiving prior hospice care significantly increased the odds of multiple ED visits, while new cancer-related ED visits independently increased the odds of hospitalisation of patients with cancer. This is the first study to report these associations from a Central-Eastern European country. Our study may shed light on the specific challenges of EDs in general and particularly faced by countries in the region.

Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes.

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2-1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

The relationship between single nucleotide polymorphisms and skin cancer susceptibility: A systematic review and network meta-analysis.

Background: Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk. Methods: PubMed, Embase, and Web of Science were searched for articles including "SNP" and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals (CIs) were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The P-score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type. Results: A total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model. Conclusions: According to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.

Endoluminal Suture-technique for the Stomach Closure of an Experimental Model.

BACKGROUND/AIM: In the modern minimally invasive era, diagnostic and therapeutic endoscopic interventions are one of the most emerging fields. For the new operational techniques, it is a major aim to develop reliable instruments, such as suturing devices for flexible endoscopes. The aim of this study was to assess the feasibility of a safe and reproducible suturing technique with an endoluminal suturing device. MATERIALS AND METHODS: The evaluation of the technique was performed in twenty explanted special prepared porcine stomachs. Three different techniques were compared, single stitches, figure-of-eight, or Z-pattern and running sutures in terms of suturing time and bursting pressure. After verification of the reliability of the method, a 3 cm long full thickness incision on the stomach was closed with the endoscopic suturing device in four surviving animals. RESULTS: In our ex vivo studies, we have shown that the figure of 8 or Z- technique is the most optimal for stomach closure without considerable time-cost, thus this technique was chosen as the standard method for the in vivo study. The endoscopic stomach wall suturing was successful in all four cases, the postoperative period was uneventful and ended on the tenth postoperative day with autopsy. CONCLUSION: With the applied suturing device, the endoscopic suturing of the stomach is safe and reproducible, thus a human application may also be justified.

Microarray data analysis to identify miRNA biomarkers and construct the lncRNA-miRNA-mRNA network in lung adenocarcinoma.

MicroRNAs (miRNAs), regulatory noncoding RNAs, are involved in gene regulation and may play a role in cancer development. The aim of this study was to identify miRNAs involved in lung adenocarcinoma (LUAD) using bioinformatics analysis. MiRNA (GSE135918), mRNA (GSE136043) and lncRNA (GSE130779) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed miRNAs (DEMis), mRNAs (DEMs), and lncRNA (DELs) in LUAD. We used DEMs for functional enrichment analysis. MiRNA expression quantification from The Cancer Genome Atlas (TCGA) was used to validate DEMis. LncBase Predicted v.2, Targetscan, and MiRBase were used to predict lncRNAs and mRNAs. The LUAD data in TCGA were used for overall survival (OS) analysis. We screened the downregulation of 8 DEMis and upregulation of 6 DEMis, and found that 70 signal pathways changed. We chose 3 relevant signaling pathways in lung cancer development, WNT, PI3K-Akt, and Notch, and scanned for mRNAs involved in them that are potential targets of these miRNAs. Then a lncRNA-miRNA-mRNA network was constructed. We also found 7 miRNAs that were associated with poor OS in LUAD. Low expression level of hsa-miR-30a was highly associated with poor OS in LUAD (P < .001) and the target genes of hsa-miR-30a-3p were abundant in the Wnt and AKT signaling pathways. In addition, our results reported for the first time that hsa-miR-3944 and hsa-miR-3652 were highly expressed in LUAD. And the high expression level of hsa-miR-3944 was associated with poor OS (P < .05). Hsa-miR-30a-3p may suppress the occurrence and progression of lung cancer through Wnt and AKT signaling pathways and become a good biomarker in LUAD. Hsa-miR-3944 and hsa-miR-3652 may serve as new biomarkers in LUAD.

Main reasons and predictive factors of cancer-related emergency department visits in a Hungarian tertiary care center.

BACKGROUND: Identifying the reasons for the Emergency Department (ED) visit of patients with cancer would be essential for possibly decreasing the burden of ED use. The aim of our study was to analyze the distribution of the demographic and clinical parameters of patients with cancer based on the reasons for the ED visits and to identify possible predictive factors for their visits. METHODS: This retrospective study, carried out at a large, public tertiary hospital in Hungary, involved all patients 18 years or over, who had received a cancer diagnosis latest within five years of their visit to the ED in 2018. Demographic and clinical characteristics were collected partly via automated data collection and partly through the manual chart review by a team of experts, including six emergency physicians and an oncologist. Five main reasons for the ED visit were hypothesized, pilot-tested, then identified, including those with cancer-related ED visits (whose visit was unambiguously related to their cancer illness) and those with non-cancer-related ED visits (whose visit to the ED was in no way associated with their cancer illness.) A descriptive approach was used for data analysis and binary logistic regression was used to determine predictive factors for patients with cancer visiting the ED. RESULTS: 23.2% of the altogether 2383 ED visits were directly cancer-related, and these patients had a significantly worse overall survival than patients with non-cancer related ED visits. Age 65 or below (Odds Ratio: 1.51), presence of two more comorbidities (OR: 7.14), dyspnea as chief complaint (OR: 1.52), respiratory cancer (OR: 3.37), any prior chemotherapy (OR: 1.8), any prior immune/biological treatment (OR: 2.21), any prior Best Supportive Care/palliative care (OR: 19.06), or any prior hospice care (OR: 9.43), and hospitalization (OR:2.88) were independent risk factors for the ED visit to be cancer-related. CONCLUSIONS: Our study is the first to identify independent predictive factors of ED use by patients with cancer based on the chief cause of their visit in the Central and Eastern European region. These results may provide important information for the development of algorithms intended to identify the needs of care of patients with cancer at the ED.

Association of antibiotic-consumption patterns with the prevalence of hematological malignancies in European countries.

Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009-2019) and the incidence rate of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0.029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0.001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = - 0.460, p = 0.011), and quinolone (r = - 0.380, p = 0.038). The incidence of LEU did not show any positive or negative association with any antibiotic classes using Spearman calculation. Multivariate ordinal logistic regression (OR) indicated increased risk between HL and the total consumption of systemic antibiotics (J01 p: 0.038), and tetracyclin (J01A p: 0.002). Similarly, increased risk has been detected between the MM and tetracyclin (J01A p: 0.02), and narrow spectrum, beta-lactamase resistant penicillin (J01CF p: 0.042) and decreased risk between cephalosporin and MM (J01D p:0.022). LEU showed increased risk with the consumption of macrolides (p: 0.047).

The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

Changes in miR-124-1, miR-212, miR-132, miR-134, and miR-155 Expression Patterns after 7,12-Dimethylbenz(a)anthracene Treatment in CBA/Ca Mice.

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents.

Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model.

DNA methylation is an epigenetic mechanism that is crucial for mammalian development and genomic stability. Aberrant DNA methylation changes have been detected not only in malignant tumor tissues; the decrease of global DNA methylation levels is also characteristic for aging. The consumption of extra virgin olive oil (EVOO) as part of a balanced diet shows preventive effects against age-related diseases and cancer. On the other hand, consuming trans fatty acids (TFA) increases the risk of cardiovascular diseases as well as cancer. The aim of the study was to investigate the LINE-1 retrotransposon (L1-RTP) DNA methylation pattern in liver, kidney, and spleen of mice as a marker of genetic instability. For that, mice were fed with EVOO or TFA and were pretreated with environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-a harmful substance known to cause L1-RTP DNA hypomethylation. Our results show that DMBA and its combination with TFA caused significant L1-RTP DNA hypomethylation compared to the control group via inhibition of DNA methyltransferase (DNMT) enzymes. EVOO had the opposite effect by significantly decreasing DMBA and DMBA + TFA-induced hypomethylation, thereby counteracting their effects.

Identification of the main genetic clusters of avian reoviruses from a global strain collection.

Introduction: Avian reoviruses (ARV), an important pathogen of poultry, have received increasing interest lately due to their widespread occurrence, recognized genetic diversity, and association to defined disease conditions or being present as co-infecting agents. The efficient control measures require the characterization of the available virus strains. Methods: The present study describes an ARV collection comprising over 200 isolates from diagnostic samples collected over a decade from 34 countries worldwide. One hundred and thirty-six ARV isolates were characterized based on σC sequences. Results and discussion: The samples represented not only arthritis/tenosynovitis and runting-stunting syndrome, but also respiratory symptoms, egg production problems, and undefined disease conditions accompanied with increased mortality, and were obtained from broiler, layer or breeder flocks. In 31 percent of the cases other viral or bacterial agents were demonstrated besides ARV. The most frequent co-infectious agent was infectious bronchitis virus followed by infectious bursal disease virus and adenoviruses. All isolates could be classified in one of the major genetic clusters, although we observed marked discrepancies in the genotyping systems currently in use, a finding that made genotype assignment challenging. Reovirus related clinical symptoms could not be unequivocally connected to any particular virus strains belonging to a specific genetic group, suggesting the lack of strict association between disease forms of ARV infection and the investigated genetic features of ARV strains. Also, large genetic differences were seen between field and vaccine strains. The presented findings reinforce the need to establish a uniform, widely accepted molecular classification scheme for ARV and further, highlight the need for ARV strain identification to support more efficient control measures.

The effects of flavonoids, green tea polyphenols and coffee on DMBA induced LINE-1 DNA hypomethylation.

The intake of carcinogenic and chemopreventive compounds are important nutritional factors related to the development of malignant tumorous diseases. Repetitive long interspersed element-1 (LINE-1) DNA methylation pattern plays a key role in both carcinogenesis and chemoprevention. In our present in vivo animal model, we examined LINE-1 DNA methylation pattern as potential biomarker in the liver, spleen and kidney of mice consuming green tea (Camellia sinensis) extract (catechins 80%), a chinese bayberry (Morella rubra) extract (myricetin 80%), a flavonoid extract (with added resveratrol) and coffee (Coffee arabica) extract. In the organs examined, carcinogen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hypomethylation was prevented by all test materials except chinese bayberry extract in the kidneys. Moreover, the flavonoid extract caused significant hypermethylation in the liver compared to untreated controls and to other test materials. The tested chemopreventive substances have antioxidant, anti-inflammatory properties and regulate molecular biological signaling pathways. They increase glutathione levels, induce antioxidant enzymes, which decrease free radical damage caused by DMBA, and ultimately, they are able to increase the activity of DNA methyltransferase enzymes. Furthermore, flavonoids in the liver may inhibit the procarcinogen to carcinogen activation of DMBA through the inhibition of CYP1A1 enzyme. At the same time, paradoxically, myricetin can act as a prooxidant as a result of free radical damage, which can explain that it did not prevent hypomethylation in the kidneys. Our results demonstrated that LINE-1 DNA methylation pattern is a useful potential biomarker for detecting and monitoring carcinogenic and chemopreventive effects of dietary compounds.

Genome sequencing of a novel variant of fowl adenovirus B reveals mosaicism in the pattern of homologous recombination events.

We determined the genomic sequence of a Ukrainian strain of fowl adenovirus B (FAdV-B). The isolate (D2453/1) shared 97.2% to 98.4% nucleotide sequence identity with other viruses belonging to the species Fowl aviadenovirus B. Marked genetic divergence was seen in the hexon, fiber, and ORF19 genes, and phylogenetic analysis suggested that recombination events had occurred in these regions. Our analysis revealed mosaicism in the recombination patterns, a finding that has also been described in the genomes of strains of FAdV-D and FAdV-E. The shared recombination breakpoints, affecting the same genomic regions in viruses belonging to different species, suggest that similar selection mechanisms are acting on the key neutralization antigens and epitopes in viruses of different FAdV species.

Tobacco Smoking and Smokeless Tobacco Use among Domestic and International Medical Students in Hungary.

BACKGROUND: Medical students as future physicians will have an important role in tobacco control; therefore, their tobacco use behavior is of particular interest. Consumption of combustible tobacco (cigarettes, waterpipes, cigars, and pipes) is prevalent throughout Europe, whereas smokeless tobacco use is common mainly in the Nordic countries. Objectives: Aim of our study is to assess tobacco use among medical students from different countries studying in Hungary with special focus on students from Norway where smokeless tobacco is widely used. A self-administered questionnaire survey was carried out to measure current tobacco use. Results: The survey included 1337 students from Hungary, Norway, Germany, and from other countries (Multinational group). The lowest prevalence of cigarette smoking was found among students from Norway (13.0%) when compared with students from Hungary (21.5%), Germany (34.2%), or with students in the Multinational group (29.5%). Conversely, prevalence of smokeless tobacco use was the highest among students from Norway (40.9%) when compared with students from Hungary (1.4%), Germany (2.6%), or with students in the Multinational group (6.2%). Waterpipes, cigars, and pipes were rarely used, mostly only 1-3 times a month in all groups. More than half of Norwegian students used some form of tobacco (smokeless and/or combustible tobacco). Conclusions: Considering the impending role of medical students in tobacco control, faculties of medicine should sensitize their students on the topic of possible health risks associated with combustible and smokeless tobacco products. Culturally tailored tobacco cessation programs need to be offered to medical students coming from different cultural backgrounds.