Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Corrigendum: Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary.

[This corrects the article DOI: 10.3389/pore.2024.1611497.].

Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary.

Purpose: This study aimed to provide real-world evidence on the characteristics, treatment patterns, and outcomes of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) treatment in Hungary between 2011 and 2019. Patients and methods: This nationwide, retrospective study included patients who were newly diagnosed with CML in Hungarian clinical practice between January 2011 and December 2019. The analysis was based on the reimbursed prescription claims for imatinib, bosutinib, dasatinib, nilotinib, or ponatinib with the ICD-10 code C9210 in a public pharmacy between January 2009 and December 2019 using data from the National Health Insurance Fund (NHIF) of Hungary. CML incidence and prevalence, TKI treatment patterns, comorbidities, and overall survival (OS) were examined. Results: Between 2011 and 2019, altogether 1,407 patients were diagnosed with CML, with an annual average of 156 patients. The number of patients newly initiating first-line TKI therapy for CML significantly increased between 2011 and 2019 (2011: n = 136 vs. 2019: n = 191; p = 0.0043). Nilotinib was typically prescribed for younger patients (≤64 years), while older patients (≥65 years) mostly received imatinib. The most common comorbidity of CML patients was hypertension, and the proportion of patients with other malignancies was relatively high in all treatment groups. 5-year OS was 77.1% during the whole study period. Patients initiating first-line TKI treatment for CML in 2015 had significantly better 4-year OS compared to those starting treatment in 2011 (82.4% vs. 73.5%, respectively, (HR 0.53 (95%CI 0.32-0.87) p = 0.0118). Conclusion: This study is the first to provide insights into the characteristics, treatment patterns, and outcomes of CML patients treated with TKIs in Hungarian clinical practice between 2011 and 2019. We found slightly lower OS rates compared to other European countries, however, there was a statistically significant improvement in 4-year OS during the study period. The management of CML was in line with international guidelines and recommendations.

Assessment of bronchodilator responsiveness to salbutamol or ipratropium using different criteria in treatment-naïve patients with asthma and COPD.

Background: The criteria for significant bronchodilator responsiveness (BDR) were published in 2005 by the European Respiratory Society/American Thoracic Society, which were revised in 2021, however, data on the agreement between these two recommendations in untreated patients with airflow limitation are missing. Aims: We aimed to study BDR to salbutamol (SABA) or ipratropium bromide (SAMA) in patients with suspected bronchial asthma or COPD at initial clinical presentation using the 2005 and 2021 criteria and explore clinical factors associated with BDR+. Methods: Symptomatic, treatment-naïve patients with expiratory airflow limitation (n = 105, 57 men, age (mean ± standard deviation): 65 ± 10 years) underwent BDR testing with 400 mcg salbutamol (day 1) or 80 mcg ipratropium bromide (day 2) and BDR was measured after 15 and 30 minutes. Clinical factors with risk for BDR+ were assessed with binomial logistic regression analysis. Results: We found a good agreement between the number of 2005-BDR+ and 2021-BDR+ patients at 15 and 30 minutes post-salbutamol and post-ipratropium (88.6-94.8%). More patients showed BDR+ after 30 minutes than following 15 minutes using either criterion. When results at 30 minutes are considered, the number of patients with 2005-BDR+ (82%) was higher than that of 2021-BDR+ (75%), with the proportion of SAMA+ patients being higher than that of SABA+ (2005: 70% vs. 49%, Fisher exact p < 0.01; 2021: 64% vs. 41%, p = 0.001). 2005-BDR+ and 2021-BDR+ to SABA were associated with decreasing pre-BD FEV1% predicted and the presence of cough. More patients with asthma were in the SABA+ group compared to the SAMA+ group (2005: 71% vs. 53%, Fischer exact p = 0.04; 2021: 77% vs. 52%, p = 0.02). Conclusions: Fewer patients show BDR+ according to the 2021 criteria in comparison with the 2005 recommendations, and protocols for BDR testing may consider the assessment of response to both SABA and SAMA after 30 minutes.

Investigating the Prevalence of Paratuberculosis in Hungarian Large-Scale Dairy Herds and the Success of Control Measures over Four Years.

Paratuberculosis (PTB) is a severe, slow-developing, untreatable disease of ruminants. Worldwide, the disease affects more than 50% of herds in the dairy industry, and causes substantial economic losses for dairy producers. Diagnostic tests show limited sensitivity, especially in the early stages of the disease. Our study aimed to investigate the seroprevalence of Mycobacterium avium ssp. paratuberculosis (MAP) in large-scale dairy herds in Hungary, in association with the self-reported presence or absence of screening and intervention measures against MAP transmission. We processed data from 42 large-scale Holstein Friesian farms in Hungary between 1 January 2018 and 31 December 2021. An average of 32,009 (min.: 31,702; max.: 32,207) animals were blood sampled yearly (127,372 in total during the four years), corresponding to 15% of the Hungarian dairy cattle population. All female cattle older than 2 years were blood sampled on the farms enroled in the study. The samples were tested using a commercial ELISA (IDEXX paratuberculosis screening Ab test). Farm managers were interviewed about their on-farm diagnostic and intervention approaches using a uniform questionnaire, including questions on the level of awareness, frequency of ELISA and PCR testing, and their strategies for culling adult animals and reducing transmission to newborn calves. By comparing the annual rate of change in seroprevalence and the amount of change observed during the four-year period, we concluded that test-and-cull strategies implemented in parallel with newborn calf management that aimed at preventing MAP transmission were superior to test-and-cull strategies alone; moreover, fortifying culling decision making via additional ELISA and PCR tests is superior to using a single ELISA result. For farms that carried out a complex program with both "test-and-cull" and proper newborn calf management, there was a proportional reduction in apparent seroprevalence at an average of 22.8% per year. Fifteen of the sampled farms had no measures in place to control paratuberculosis. On these farms, the seroprevalence increased by 12.1% per year on average.

KSHV 3.0: a state-of-the-art annotation of the Kaposi's sarcoma-associated herpesvirus transcriptome using cross-platform sequencing.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a large, oncogenic DNA virus belonging to the gammaherpesvirus subfamily. KSHV has been extensively studied with various high-throughput RNA-sequencing approaches to map the transcription start and end sites, the splice junctions, and the translation initiation sites. Despite these efforts, the comprehensive annotation of the viral transcriptome remains incomplete. In the present study, we generated a long-read sequencing data set of the lytic and latent KSHV transcriptome using native RNA and direct cDNA-sequencing methods. This was supplemented with Cap Analysis of Gene Expression sequencing based on a short-read platform. We also utilized data sets from previous publications for our analysis. As a result of this combined approach, we have identified a number of novel viral transcripts and RNA isoforms and have either corroborated or improved the annotation of previously identified viral RNA molecules, thereby notably enhancing our comprehension of the transcriptomic architecture of the KSHV genome. We also evaluated the coding capability of transcripts previously thought to be non-coding by integrating our data on the viral transcripts with translatomic information from other publications.IMPORTANCEDeciphering the viral transcriptome of Kaposi's sarcoma-associated herpesvirus is of great importance because we can gain insight into the molecular mechanism of viral replication and pathogenesis, which can help develop potential targets for antiviral interventions. Specifically, the identification of substantial transcriptional overlaps by this work suggests the existence of a genome-wide interference between transcriptional machineries. This finding indicates the presence of a novel regulatory layer, potentially controlling the expression of viral genes.

Hypoxia and HIF-1α promote lytic de novo KSHV infection.

IMPORTANCE: The current view is that the default pathway of Kaposi's sarcoma-associated herpesvirus (KSHV) infection is the establishment of latency, which is a prerequisite for lifelong infection and viral oncogenesis. This view about KSHV infection is supported by the observations that KSHV latently infects most of the cell lines cultured in vitro in the absence of any environmental stresses that may occur in vivo. The goal of this study was to determine the effect of hypoxia, a natural stress stimulus, on primary KSHV infection. Our data indicate that hypoxia promotes euchromatin formation on the KSHV genome following infection and supports lytic de novo KSHV infection. We also discovered that hypoxia-inducible factor-1α is required and sufficient for allowing lytic KSHV infection. Based on our results, we propose that hypoxia promotes lytic de novo infection in cells that otherwise support latent infection under normoxia; that is, the environmental conditions can determine the outcome of KSHV primary infection.

To Eat or Not to Eat?-Food Safety Aspects of Essential Metals in Seafood.

The popularity of seafoods is high due to their superb dietary properties and healthy composition. However, it is crucial to understand whether they adequately contribute to our essential nutritional needs. Small amounts of essential metals are indispensable in the human body to proper physiological functioning; their deficiency can manifest in various sets of symptoms that can only be eliminated with their intake during treatment or nutrition. However, the excessive consumption of metals can induce undesirable effects, or even toxicosis. Shellfish, oyster, and squid samples were collected directly from a fish market. After sample preparation, the concentration of essential metals (cobalt, chromium, copper, manganese, molybdenum, nickel, and zinc) was detected by Inductively Coupled Plasma Optical Emission Spectrometry. The results were analyzed statistically using ANOVA and two-sample t-tests. The average concentration of the investigated essential elements and the calculated burden based on the consumption were below the Recommended Dietary Allowances and Tolerable Upper Intake Levels. Based on these results, the trace element contents of the investigated seafoods do not cover the necessary recommended daily intake of them, but their consumption poses no health hazard due to their low levels.

KSHV 3.0: A State-of-the-Art Annotation of the Kaposi's Sarcoma-Associated Herpesvirus Transcriptome Using Cross-Platform Sequencing.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a large, oncogenic DNA virus belonging to the gammaherpesvirus subfamily. KSHV has been extensively studied with various high-throughput RNA-sequencing approaches to map the transcription start and end sites, the splice junctions, and the translation initiation sites. Despite these efforts, the comprehensive annotation of the viral transcriptome remains incomplete. In the present study, we generated a long-read sequencing dataset of the lytic and latent KSHV transcriptome using native RNA and direct cDNA sequencing methods. This was supplemented with CAGE sequencing based on a short-read platform. We also utilized datasets from previous publications for our analysis. As a result of this combined approach, we have identified a number of novel viral transcripts and RNA isoforms and have either corroborated or improved the annotation of previously identified viral RNA molecules, thereby notably enhancing our comprehension of the transcriptomic architecture of the KSHV genome. We also evaluated the coding capability of transcripts previously thought to be non-coding, by integrating our data on the viral transcripts with translatomic information from other publications.

KSHV RTA utilizes the host E3 ubiquitin ligase complex RNF20/40 to drive lytic reactivation.

IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is a cancer-causing human herpesvirus that establishes a persistent infection in humans. The lytic viral cycle plays a crucial part in lifelong infection as it is involved in the viral dissemination. The master regulator of the KSHV lytic replication cycle is the viral replication and transcription activator (RTA) protein, which is necessary and sufficient to push the virus from latency into the lytic phase. Thus, the identification of host factors utilized by RTA for controlling the lytic cycle can help to find novel targets that could be used for the development of antiviral therapies against KSHV. Using a proteomics approach, we have identified a novel interaction between RTA and the cellular E3 ubiquitin ligase complex RNF20/40, which we have shown to be necessary for promoting RTA-induced KSHV lytic cycle.

Significant changes in advanced lung cancer survival during the past decade in Hungary: impact of modern immunotherapy and the COVID-19 pandemic.

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database. Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology. Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period. Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic.

Identification of herpesvirus transcripts from genomic regions around the replication origins.

Long-read sequencing (LRS) techniques enable the identification of full-length RNA molecules in a single run eliminating the need for additional assembly steps. LRS research has exposed unanticipated transcriptomic complexity in various organisms, including viruses. Herpesviruses are known to produce a range of transcripts, either close to or overlapping replication origins (Oris) and neighboring genes related to transcription or replication, which possess confirmed or potential regulatory roles. In our research, we employed both new and previously published LRS and short-read sequencing datasets to uncover additional Ori-proximal transcripts in nine herpesviruses from all three subfamilies (alpha, beta and gamma). We discovered novel long non-coding RNAs, as well as splice and length isoforms of mRNAs. Moreover, our analysis uncovered an intricate network of transcriptional overlaps within the examined genomic regions. We demonstrated that herpesviruses display distinct patterns of transcriptional overlaps in the vicinity of or at the Oris. Our findings suggest the existence of a 'super regulatory center' in the genome of alphaherpesviruses that governs the initiation of both DNA replication and global transcription through multilayered interactions among the molecular machineries.

Interaction of biomolecules with anatase, rutile and amorphous TiO2 surfaces: A molecular dynamics study.

The adhesion of biomolecules to dental and orthopedic implants is a fundamental step in the process of osseointegration. Short peptide motifs, such as RGD or KRSR, carried by extracellular matrix proteins or coated onto implant surfaces, accelerate cell adhesion and tissue formation. For this reason, understanding the binding mechanisms of adhesive peptides to oxidized surfaces of titanium implants is of paramount importance. We performed molecular dynamics simulations to compare the adhesion properties of 6 peptides, including the tripeptide RGD, its variants KGD and LGD, as well as the tetrapeptide KRSR, its variant LRSR and its truncated version RSR, on anatase, rutile, and amorphous titanium dioxide (TiO2) surfaces. The migration of these molecules from the water phase to the surface was simulated in an aqueous environment. Based on these simulations, we calculated the residence time of each peptide bound to the three different TiO2 structures. It was found that the presence of an N-terminal lysine or arginine amino acid residue resulted in more efficient surface binding. A pulling simulation was performed to detach the adhered molecules. The maximum pulling force and the binding energy were determined from the results of these simulations. The tri- and tetrapeptides had slightly greater adhesion affinity to the amorphous and anatase structure than to rutile in general, however specific surface and peptide binding characters could be detected. The binding energies obtained from our simulations allowed us to rank the adhesion strengths of the studied peptides.

Ultrasound examination of the teat parameters of mastitis and healed udder quarters.

A healthy udder is important for economical and hygienic milk production. In this study we determined the teat parameters, measured during milking, in the presence of mastitis and after its recovery. The length of the streak canal, the area of the teat end and the area of the pars papillaris of 52 Holstein-Friesian cows were examined by ultrasound before, immediately after, and two hours after milking. Pars papillaris size before milking was higher in the presence of disease (P = 0.011), but was larger before and two hours after milking (P = 0.047 and P = 0.024) with more severe mastitis. During mastitis and recovery, the dimensions of the streak canal (P=0.056-0.934) and teat end (P=0.156-0.420) did not differ from each other. The obtained results show that during mastitis, coagulated milk dilates the pars papillaris better (P=0.011) than the higher milk production of the cured cow. After more severe mastitis, regeneration of the pars papillaris as well as post-milking regeneration also takes place more slowly. The size and size changes of the streak canal and teat end are not affected by the presence or healing of the udder inflammation.

Incremental cost of premature birth - a public health care payer perspective from Hungary.

BACKGROUND: Preterm birth remains a significant burden to families, health systems and societies. The aim was to quantify the incremental prematurity-related public health expenditure in Hungary and to estimate the potential impact of a decrease in the prevalence of prematurity on the public payer's spending. METHODS: Over a 6-year time horizon, public financing data of inpatient, outpatient and pharmaceutical care for children born at ≥ 25 weeks of gestation in 2009/2010 were retrieved from the Hungarian National Health Insurance Fund database. In descriptive analysis, the public payer's spending was given as cost/capita. The impact of a decrease in prematurity prevalence was specified as the total budget impact. An exchange rate of 294 Hungarian forint/Euro was applied. RESULTS: A total of 93,124 children (including 8.6% who were premature babies) were included in the analysis. A strong negative relationship was shown between gestational age and per capita cost. The 6-year cost of care for the cohort born at 26 weeks of gestation (28,470 Euro per capita) was 24 times higher than that for the cohort born at 40 weeks. First-year inpatient spending accounted for the largest proportion of total health care spending across all gestational ages. All investigated prematurity complications (retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular cerebral bleeding and leukomalacia) resulted in additional significant incremental spending. If 70% of pregnancies ending with preterm birth could be prolonged by 1 week, the savings would be almost 7.0 million Euros in the first 6 years of life. CONCLUSION: This comprehensive analysis of prematurity-related health care spending confirmed that premature infants have much higher costs for care than those born at term in Hungary. These quantitative outcomes can provide essential inputs for the cost-effectiveness analysis of medical technologies and public health interventions that can decrease the prevalence of premature birth. TRIAL REGISTRATION: Not applicable.

Automatic Detection of Moths (Lepidoptera) with a Funnel Trap Prototype.

Monitoring insect populations is essential to optimise pest control with the correct protection timing and the avoidance of unnecessary insecticide use. Modern real-time monitoring practices use automatic insect traps, which are expected to be able to estimate the population sizes of pest animals with high species specificity. There are many solutions to overcome this challenge; however, there are only a few data that consider their accuracy under field conditions. This study presents an opto-electronic device prototype (ZooLog VARL) developed by us. A pilot field study evaluated the precision and accuracy of the data filtering using an artificial neural network(ANN) and the detection accuracy of the new probes. The prototype comprises a funnel trap, sensor-ring, and data communication system. The main modification of the trap was a blow-off device that prevented the escape of flying insects from the funnel. These new prototypes were tested in the field during the summer and autumn of 2018, detecting the daily and monthly flight of six moth species (Agrotis segetum, Autographa gamma, Helicoverpa armigera, Cameraria ohridella, Grapholita funebrana, Grapholita molesta). The accuracy of ANN was always higher than 60%. In the case of species with larger body sizes, it reached 90%. The detection accuracy ranged from 84% to 92% on average. These probes detected the real-time catches of the moth species. Therefore, weekly and daily patterns of moth flight activity periods could be compared and displayed for the different species. This device solved the problem of multiple counting and gained a high detection accuracy in target species cases. ZooLog VARL probes provide the real-time, time-series data sets of each monitored pest species. Further evaluation of the catching efficiency of the probes is needed. However, the prototype allows us to follow and model pest dynamics and may make more precise forecasts of population outbreaks.

Urban soil quality deteriorates even with low heavy metal levels: An arthropod-based multi-indices approach.

Urban-induced habitat conversion drastically changes soil life in a variety of ways. Soil sealing, human disturbance, habitat fragmentation, industrial and vehicular pollution are the main causes of urban soil degradation. Soil arthropods, as one of the most abundant and diverse group of soil fauna, are involved in many soil processes that are of great importance in maintaining soil health and multifunctionality. Nevertheless, soil quality is still mainly characterized by physical, chemical, and microbiological parameters. Here, we assessed and compared the biological soil quality in woody (REF: reference forest, REM: remnant forest) and nonwoody (TURF: public turfgrass, and RUD: ruderal habitat) types of urban green spaces along a disturbance and management intensity gradient in the Budapest metropolitan area (Hungary), using community metrics and soil arthropod-based indicators. Vegetation cover and landscape characteristics of study sites were quantified through vegetation and urbanization indices, respectively. Basic soil properties, total and bioavailable concentrations of the main heavy metals (Cd, Co, Hg, Ni, Zn) were also measured. Acari, Collembola, and Hymenoptera (mainly Formicidae) were the most abundant groups. Litter-dweller taxa, particularly Protura, proved to be the most sensitive to urban disturbance. Representatives of Hemiptera, Diptera, Symphyla, and Pauropoda were common in low densities. The taxonomic diversity of soil arthropod assemblages in nonwoody and woody habitats was similar. Although the integrated faunal indices showed no differences among soil habitat types, they provided different responses and, consequently, different information. Our findings demonstrated that the biological quality and arthropod community structure of soils were strongly impacted by soil C/N and heavy metal contamination. We found that low and moderate levels of pollution have adverse effects on edaphic fauna, suggesting biological degradation of soils, even below pollution limits. Nevertheless, more disturbed urban green spaces have been shown to play a significant role in maintaining belowground biodiversity, thereby soil functions.

Different Conical Angle Connection of Implant and Abutment Behavior: A Static and Dynamic Load Test and Finite Element Analysis Study.

Dental implants are artificial dental roots anchoring prosthetic restorations to replace natural teeth. Dental implant systems may have different tapered conical connections. Our research focused on the mechanical examination of implant-superstructure connections. Thirty-five samples with 5 different cone angles (24°, 35°, 55°, 75°, and 90°) were tested for static and dynamic loads, carried out by a mechanical fatigue testing machine. Fixing screws were fixed with a torque of 35 Ncm before measurements. For static loading, samples were loaded with a force of 500 N in 20 s. For dynamic loading, the samples were loaded for 15,000 cycles with a force of 250 ± 150 N. In both cases, the compression resulting from load and reverse torque was examined. At the highest compression load of the static tests, a significant difference (p = 0.021) was found for each cone angle group. Following dynamic loading, significant differences (p < 0.001) for the reverse torques of the fixing screw were also shown. Static and dynamic results showed a similar trend: under the same loading conditions, changing the cone angle-which determines the relationship between the implant and the abutment-had led to significant differences in the loosening of the fixing screw. In conclusion, the greater the angle of the implant-superstructure connection, the smaller the screw loosening due to loading, which may have considerable effects on the long-term, safe operation of the dental prosthesis.

Protein Degradation by Gammaherpesvirus RTAs: More Than Just Viral Transactivators.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the Gammaherpesvirus subfamily that encodes several viral proteins with intrinsic E3 ubiquitin ligase activity or the ability to hijack host E3 ubiquitin ligases to modulate the host's immune response and to support the viral life cycle. This review focuses specifically on how the immediate-early KSHV protein RTA (replication and transcription activator) hijacks the host's ubiquitin-proteasome pathway (UPP) to target cellular and viral factors for protein degradation to allow for robust lytic reactivation. Notably, RTA's targets are either potent transcription repressors or they are activators of the innate and adaptive immune response, which block the lytic cycle of the virus. This review mainly focuses on what is currently known about the role of the E3 ubiquitin ligase activity of KSHV RTA in the regulation of the KSHV life cycle, but we will also discuss the potential role of other gammaherpesviral RTA homologs in UPP-mediated protein degradation.

Quantitative Analysis of Inflammatory Uterine Lesions of Pregnant Gilts with Digital Image Analysis Following Experimental PRRSV-1 Infection.

Reproductive disorders caused by porcine reproductive and respiratory syndrome virus-1 are not yet fully characterized. We report QuPath-based digital image analysis to count inflammatory cells in 141 routinely, and 35 CD163 immunohistochemically stained endometrial slides of vaccinated or unvaccinated pregnant gilts inoculated with a high or low virulent PRRSV-1 strain. To illustrate the superior statistical feasibility of the numerical data determined by digital cell counting, we defined the association between the number of these cells and endometrial, placental, and fetal features. There was strong concordance between the two manual scorers. Distributions of total cell counts and endometrial and placental qPCR results differed significantly between examiner1's endometritis grades. Total counts' distribution differed significantly between groups, except for the two unvaccinated. Higher vasculitis scores were associated with higher endometritis scores, and higher total cell counts were expected with high vasculitis/endometritis scores. Cell number thresholds of endometritis grades were determined. A significant correlation between fetal weights and total counts was shown in unvaccinated groups, and a significant positive correlation was found between these counts and endometrial qPCR results. We revealed significant negative correlations between CD163+ counts and qPCR results of the unvaccinated group infected with the highly virulent strain. Digital image analysis was efficiently applied to assess endometrial inflammation objectively.