Search

Objective: The aim of the present study was to evaluate the long-term clinical survival and success of chairside-fabricated single-tooth monolithic zirconia restorations on posterior teeth using the speed sintering process. Materials and Methods: Between 2012 and 2022, 250 single-tooth crowns were fabricated for 193 patients using the CEREC® chairside workflow. Restorations were fabricated from monolithic 3Y-TZP zirconia (InCoris TZI, Dentsply Sirona©, Bensheim, Germany) as full-contour crowns. The same clinician performed all procedures. Luting was performed using self-adhesive resin-based cements or glass ionomer cement. Retrospective analysis was conducted, defining survival as crowns still in function regardless of any interventions, and success as crowns that remained functional without the need for intervention. Statistical analysis was performed using Kaplan–Meier analysis, considering “refabrication” and “intervention” as endpoints. Results: Of the 250 crowns, a total of 162 (64.8%) crowns showed success. Over the whole observation period, 44 crowns (17.6%) required refabrication, and 88 (35.2%) required intervention. Mean survival without refabrication was 7.43 years, with a 5- and 7.5-year survival of 86.9% and 76.6%. The mean survival without intervention was 6.5 years, with a 5- and 7.5-year survival of 70.8% and 59.9%. Conclusions: Under appropriate technical conditions, chairside-fabricated 3Y-TZP zirconia single-tooth crowns represent a viable fabrication method. Neither the cementation mode nor the crown position—whether on premolars or molars—significantly impacted the survival rates.

Aim: The aim of this study was to assess the usefulness of bioimpedance analysis in fluid status evaluation in patients with sepsis and septic shock admitted to the adult ICU. Materials and methods: This is a prospective, observational, clinician-blind study. The inclusion criteria were a diagnosis of sepsis at admission to ICU, a stay in ICU of at least 72 hours, and the first BIA measurement to be conducted within the first three hours of ICU admission. We took whole-body BIA measurements upon admission and every 24 hours thereafter for at least four consecutive measurements. All enteral and parenteral fluids administered to the patients were recorded, as well as the loses through drains, tubes, aspiration, and urine. The cumulative fluid balance (CFB) was calculated every 24 hours. Results: A total of 51 patients with a mean age of 62 years were included in the final analysis. CFB gradually increased during the first 72 hours of ICU stay from 2003±1331 mL at 24 hours to 3680±2368 mL at 48 hours and 5217±2642 mL at 72 hours. There was a statistically significant positive correlation between the increase in CFB and the increase in total body water, extracellular water, and overhydration. The daily changes of vector length and impedance ratio, as well as the overall 72-hour changes showed statistically significant correlation with the CFB. Conclusion: Bioimpedance analysis is a non-invasive, easy-to-use, inexpensive, portable, and fast tool for fluid status assessment. In critically ill septic patients it can be a useful tool in fluid therapy management.

The text critically examines the intricate interplay between politics, ideology, and law within the ongoing war in Ukraine. The primary aim is to comprehensively assess the multifaceted implications of the conflict for Europe’s position in the evolving global context. Through the presentation of ten key points, the author explores various topics, including the erosion of sovereignty due to the Russian intervention, the absence of formal war declarations, and the far-reaching consequences of the conflict on a global scale. Additionally, the discourse delves into the crisis facing the international legal order, the emergence of a more complex bipolar world, and the expansion of EU law at the expense of national legislation.

Aim: To compare the energy expenditure (EE) assessed by ventilator-derived carbon dioxide production (EE–VCO2-ventilator) and the energy expenditure calculated from six predictive equations with the gold standard energy expenditure measured with indirect calorimetry (IC) in mechanically ventilated patients. Materials and methods: This is a prospective, non-randomized, one-month study which included six mechanically ventilated patients with FiO2

Background: Virtual simulators are increasingly being introduced in dental education. This study investigates whether virtual simulators offer comparable or superior educational efficacy when compared to traditional phantom simulators. Materials and Methods: Participants were randomly allocated into groups: Virtual Preparation (SIM; n = 30) and Traditional Preparation (FRA; n = 30). Students were tasked with preparing tooth 36 for a full-cast crown during free practice for four days. Faculty staff provided feedback to both groups. Examinations were administered and graded by three examiners (preclinical and clinical consultants and a dental surgery consultant). Additionally, a survey was conducted to assess each training concept. Results: The FRA group achieved significantly better grades in the preparation exam evaluations by all three examiners, compared to the SIM group. Interrater reliability showed only moderate agreement, with the clinical examiner giving better grades than the other two. The questionnaire results indicate that while participants managed with the virtual system, they preferred the analog system for exams and patient preparation. Conclusion: Virtual simulators do not seem to be as good when it comes to practicing for a preparation exam or clinical preparation, especially for unexperienced students. However, they still appear to be useful as an additional tool for introducing students to the topic of preparation.

[This corrects the article DOI: 10.1371/journal.ppat.1008307.].

Chronic wounds often result in multiple infections with various kinds of bacteria and uncontrolled wound exudate, resulting in several healthcare issues. Advanced medicated nanofibres prepared by electrospinning have gained much attention for their topical application on infected chronic wounds. The objective of this work is to enhance the critical variables of ciprofloxacin-loaded polycaprolactone-silk sericin (PCL/SS-PVA-CIP) nanofibre production via the process of electrospinning. To examine the antibacterial effectiveness of PCL/SS-PVA-CIP nanocomposites, the material was tested against P. aeruginosa and S. aureus. The combination of PCL/SS-PVA-CIP exhibited potent inhibitory properties, with the most effective concentrations of ciprofloxacin (CIP) being 3 μg/g and 7.0 μg/g for each bacterium, respectively. The biocompatibility was evaluated by conducting cell reduction and proliferation studies using the human epidermal keratinocyte (HaCaT) cells and human gingival fibroblasts (HGFs) in vitro cell lines. The PCL/SS-PVA-CIP showed good cell compatibility with HaCaT and HGF cells, with effective proliferation even at antibiotic doses of up to 7.0 μg/g. The drug release effectiveness of the nanocomposites was assessed at various concentrations of CIP, resulting in a maximum cumulative release of 76.5% and 74.4% after 72 h for CIP concentrations of 3 μg/g and 7 μg/g, respectively. In summary, our study emphasizes the possibility of combining silk sericin (SS) and polycaprolactone (PCL) loading with CIP nanocomposite for wound management.

Higher plants have developed complex mechanisms to adapt to fluctuating environmental conditions with light playing a vital role in photosynthesis and influencing various developmental processes, including photomorphogenesis. Exposure to ultraviolet (UV) radiation can cause cellular damage, necessitating effective DNA repair mechanisms. Histone acetyltransferases (HATs) play a crucial role in regulating chromatin structure and gene expression, thereby contributing to the repair mechanisms. HATs facilitate chromatin relaxation, enabling transcriptional activation necessary for plant development and stress responses. The intricate relationship between HATs, light signaling pathways and chromatin dynamics has been increasingly understood, providing valuable insights into plant adaptability. This review explores the role of HATs in plant photomorphogenesis, chromatin remodeling and gene regulation, highlighting the importance of chromatin modifications in plant responses to light and various stressors. It emphasizes the need for further research on individual HAT family members and their interactions with other epigenetic factors. Advanced genomic approaches and genome-editing technologies offer promising avenues for enhancing crop resilience and productivity through targeted manipulation of HAT activities. Understanding these mechanisms is essential for developing strategies to improve plant growth and stress tolerance, contributing to sustainable agriculture in the face of a changing climate.

The efficient planning and control of timber harvesting operations is crucial to growth productivity and reducing costs, and different systems or methods are applied to obtain elevated performance. In particular, cable yarding is a highly appreciated and very efficient wood extraction method in areas that are difficult to access with ground-based extraction machines. Combined logging systems are not diffuse and not often implemented. For this reason, the use and the application of innovative methods are limited. However, some combinations have recently been observed in forest operations. This study, conducted in a deciduous stand in Bulgaria, paid attention to the combination of a tractor-mounted tower yarder (Valentini V400) with a clambunk skidder (Timberjack 1010D), aiming to examine the viability and develop the operational efficiency of the two-stage extraction system and to define the time, log volume extracted per unit by the yarder and the clambunk, and the yarding and skidding costs. The researchers carried out a time-motion study and performed a regression analysis to identify those variables that are most likely to affect the duration of work elements and productivity. For cost analysis, the COST model was used. The mean productivity of the tower yarder was 10.34 m3/PMH and 8.11 m3/SMH, while for the clambunk skidder, the productivity was 6.23 m3/PMH and 4.93 m3/SMH. The net costs for the combined logging system were calculated as 120.87 €/PMH and 14.93 €/m3. This study adds new data about the correct use of both machines, supporting their application in beech forests.

Introduction: One of the major obstetrical complications, affecting 2%–8% of all pregnancies, is preeclampsia. To predict the onset of preeclampsia, several methods have recently been put forth. The Fetal Medicine Foundation has developed combined screening that can identify the vast majority of women who will develop preeclampsia using a combination of maternal factors, obstetrical history, biochemical, and biophysical factors. Aim: The objective of the present study was to identify and analyze which classical risk factors may be independent predictors of preeclampsia, and assess their impact on this complication. In order to assess the high risk of preeclampsia, we also suggest further predictors that may optimize the risk constellation. Materials and methods: The study included 1511 pregnant women who were examined during their routine checkups in a two-phase retrospective study that took place from January 30, 2018, to August 31, 2020, in the Outpatient Department of the University Hospital in Plovdiv. All primary data were obtained from their archived medical records. Information about the maternal factors, the patients’ medical and obstetric histories, and status was obtained during the first phase of the study (11th gestation week + 0 days – 13th gestation week + 6 days). The second phase was conducted as a telephone interview (up to six months after the birth of the child): we collected data on the mode of birth, weight of the newborn, PE occurrence, at which gestation week the PE onset occurred, presence of gestational hypertension (GH) and diabetes, intrauterine growth retardation (IUGR), whether patients took aspirin and in what dosage, other complications, etc. The patients were divided into two groups: a high-risk group (with a risk for PE higher than 1:150), and a low-risk group, with or without onset of IUGR, GH, diabetes, etc. Results: The mean age of the analyzed 1511 pregnant women was 29.91±5.32 years (range 18 – 46 years). Of these, 38 (2.9%) women developed preeclampsia, and 5.9% had gestational hypertension. The classification of participants by risk of developing preeclampsia showed that 591 (39.1%) of the examined patients were reported as high-risk. All patients at risk higher than 1:150 were classified as high-risk, and it was recommended that they should take aspirin 150 mg every night from 12th to 36th week of gestation. 80.6% of the high-risk group took the medication regularly. Comparing the beta coefficients for the parameters we studied (beta coefficient indicates the predictors’ impact on PE), we established that the risk factors that are the most significant and apparently independent in predicting preeclampsia were (in ascending order): 1. Weight of newborn, β=0.157; 2. Mean arterial blood pressure (MAP), β=0.150; 3. IUGR, β=0.120; 4. Pregnancy associated plasma protein-A (PAPP-A), β=0.112; 5. Cervix length, β=0.095 Conclusions: In the analysis of the four multiple regression models, adequately describing the role (and independence) of the PE predictors – common to all pregnant women; in cases of early midterm and term PE: placental growth factor (PlGF), PAPP-A, MAP, mean Ut PI, cervical length, newborn weight, and IUGR. As common for all cases with PE, and depending on whether the PE onset was ≤32, ≤4, or ≤36 week of gestation, the following conclusions can be made: independent predictors of PE in all studied pregnant women were (indicators are ranked according to their degree of impact on the occurrence of PE): 1. MAP; 2. Intrauterine growth retardation (newborn weight is an indirect indicator of probable IUGR); 3. Pregnancy-associated protein-A; 4. Cervix length (with the corresponding standardized coefficients being β=0.150; β=0.120; β=0.112; β=0.095, respectively).

Logistic tasks are aimed at the optimal distribution of material, energy, financial and human resources. This research has a narrow field aimed at optimal management of financial resources and their redistribution. Specifically, a reinvestment policy model is derived by maximizing the profit of a business entity. Reinvestment is done with risk-free assets, but they have different maturity periods. This makes it difficult to assess the optimal investment strategy, as reinvestment can be done at the end of the maturity period. This study develops a model for a dynamic control process, which leads to the formalization of a discrete integer time optimization problem. Its solution gives a sequence of investments and a total optimal return. The solution to the problem is illustrated in an EXCEL environment. The added value of this study stems from the formalization and quantification of the model for the reinvestment strategy in the optimization problem.

AbstractThis narrative review provides a brief horizon scanning on the available literature on cost-effectiveness of therapeutic drug monitoring (TDM) in rheumatology for biological medicines. The PubMed database was used to search for articles containing the key words ‘cost-effectiveness’ AND ‘therapeutic drug monitoring’ AND ‘rheumatology’ or ‘rheumatoid’ with no limits on year of publication. CHEERS pharmacoeconomic criteria were applied to review the robustness of the studies. Out of 42 initial hits, only 4 full-text articles and 2 abstracts matched the specified search criteria fully. They conclude that proactive TDM was more cost-effective for patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab. For rheumatoid arthritis (RA) patients, the adalimumab dose tapering based on TDM led to an increased quality of life and quality-adjusted life year (QALY) gain and entailed lower costs. Patient-initiated service on the basis of TDM resulted in reductions in primary and secondary healthcare services, and hence, lower costs than the usual care. The use of a JAK1/JAK2 inhibitor instead of a biologic disease modifying drug (DMARD) in a treat-to-target approach is cost-effective in conventional synthetic DMARD refractory RA patients; monitoring of patients with chronic inflammatory diseases and low disease activity or in remission undergoing biological therapy can be achieved with less resources. The findings in our mini-review suggest that TDM might result in cost-saving. Given the benefit other patients may gain from the resources saved, we encourage further clinical and cost-effectiveness studies.

Continuous neuronal survival is vital for mammals because mammalian brains have limited regeneration capability. After neurogenesis, suppression of apoptosis is needed to ensure a neurons long-term survival. Here we describe a robust genetic program that intrinsically attenuates apoptosis competence in neurons. Developmental downregulation of the splicing regulator PTBP1 in immature neurons allows neural-specific splicing of the evolutionarily conserved Bak1 microexon 5. Exon 5 inclusion triggers nonsense-mediated mRNA decay (NMD) and unproductive translation of Bak1 transcripts (N-Bak mRNA), leading to suppression of pro-apoptotic BAK1 proteins and allowing neurons to reduce apoptosis. Germline heterozygous ablation of exon 5 increases BAK1 proteins exclusively in the brain, inflates neuronal apoptosis, and leads to early postnatal mortality. Therefore, neural-specific exon 5 splicing and depletion of BAK1 proteins uniquely repress neuronal apoptosis. Although apoptosis is important for development, attenuation of apoptosis competence through neural-specific splicing of the Bak1 microexon is essential for neuronal and animal survival.

AbstractThis study analysed the changes in the reimbursed cost, prices and utilization of biological medicines for a 5-year time horizon, encompassing three major arthropathic diagnoses, rheumatoid arthritis (RA), psoriatic arthropathies (PsA) and ankylosing spondylitis (AS), from the point of view of the third-party payer in Bulgaria. National; population based; macroeconomic; top-down budget analysis was performed based on official data about the number of inhabitants, reimbursed diagnoses and medicines, reimbursed cost, treated patients, and prices of medicines. The utilization of medicines was calculated in DDD per 1000/inh/day. There was an increase of 41% in the number of patients treated with biological medicines. The reimbursement cost of biologicals increased by 21%; however, the per-patient reimbursement costs per diagnosis fell by 40% due to price decreases. Out of 21 reimbursed diagnoses, we saw a significant difference in prevalence (612 SD in 2016 to 1216 SD in 2020; p

The RNA-binding proteins, Musashi 1 and 2, regulate splicing of photoreceptor-specific alternative exons and activate protein expression, and are essential for promoting translation of proteins required for vision and photoreceptor survival.

Takayasu arteritis (TA) is a chronic large-vessel vasculitis characterized by immune-mediated panarteritis, which predominantly affects the aorta and its main branches and is most prevalent in young women. TA is unusually associated with the presence of antiphospholipid antibodies. We present a case report of a 48-year-old Caucasian woman with acute aortic dissection as an initial feature of TA, where detailed clinical, imaging and laboratory studies were performed. Computed tomography angiography (CTA) of the chest and abdomen revealed aortic dissection DeBakey I. Bentall and De Bono surgery was performed. Additional immunological tests revealed positive antineutrophil cytoplasmic antibodies (ANCAs) with the simultaneous presence of pANCA and cANCA antibodies on indirect immunofluorescence, along with anti-MPO+PR3+antibodies positivity in the absence of a clinically relevant disease. Surprisingly, antiphospholipid antibodies (aPLs) were detected. Then, we performed a thorough review of the current literature. The coexistence of aPL antibodies and dual specificity for MPO and PR3 in a patient diagnosed with Takayasu arteritis is unusual and poses a diagnostic challenge. The presented case report outlines a rare case of aortic dissection as a presenting symptom of TA, along with atypical ANCA positivity and positive APL antibodies.

Salvage logging is increasing in Central Europe because of the growth of severe meteorological events, and timber harvesting in these conditions is challenging in terms of both productivity performances and safety of the operations. In recent years, with the increase of natural calamities, several researchers studied machinery productivity performances regarding salvage logging carried out by ground-based systems. In fact, a common post-disturbance management approach is salvage logging which consists of the widespread removal of damaged trees. In this research, system productivity and the cost of salvage logging are analysed in European beech stands affected by wet snow. The accretion of heavy wet snow poses the greatest risk to forests in the Northern Hemisphere. This type of snow attaches more effectively to tree crowns and branches when temperatures are close to freezing at the time of precipitation. As a result, trees may break or bend and may be uprooted when the soil is unfrozen. This study has been implemented to evaluate the productivity and cost-effectiveness of extraction in salvage logging deployed with a skidder in beech stands affected by two different types of wet snow damage. The results show that the productivity of the four-wheel-drive cable skidder, despite operating in salvage cutting with a removal intensity of 10%, is 14.73 m3·SMH–1, similar to skidder performances in ‘ordinary’ cuttings. Skidder’s productive time was 86% of the scheduled time, whereas the delays were due to organisational reasons, mechanical delays, and adverse weather conditions. The mean travel speed of the cable skidder obtained in this study is close to the results obtained from other studies on similar machines. The costs per unit are lower than effective cost consumptions for the other cable skidders and agricultural tractors, adapted for skidding operated in hardwood salvage logging. Therefore, under the given conditions, the operation of the fourwheel-drive cable skidder is viable from a silvicultural, technical, and economic point of view in the salvage operation logging.

This study proposes a theoretical method for evaluating the “safety against derailment” indicator of a specialized train composition for the transportation of very long rails. A composition of nine wagons, suitable for the transportation of rails with a length of 120 m in three layers, is considered. For the remaining recommended rail lengths, the number of wagons is reduced or increased, with the calculation model being modified depending on the required configuration. When the composition is in a curve with the minimum radius (R = 150 m), the rails bend, and some of them come into contact with the vertical stanchions of the wagon and cause additional lateral forces. These forces are then transferred through the wagon body, central pivot, bogie frame, and wheels and act on the wheel–rail contact points. They could potentially lead to derailment of the train composition. The goal of this study is to determine the additional lateral forces that arise because of the bent rails. For the purposes of this study, the finite element method was used. Based on the displacements of the support points of the rails (caused by the geometry of the curve), the bending line of the elastic load is determined and the forces in the supports are calculated. The resulting forces are considered when determining the derailment safety criterion. The analysis of the results shows that the wagon with fixing blocks is the most at risk of derailment. The front and intermediate wagons have criterion values very close to that of the empty wagon. This shows that the emerging horizontal elastic forces do not significantly influence the derailment process. The obtained results show that the transportation of long rails with specialized train composition can be realized on four layers. This will significantly increase the efficiency of delivering new long rails.