Effects of addition of quaternary ammonium antimicrobial compounds into root canal sealers

Objective: The aim of this study is to determine the effect of the addition of benzalkonium chloride and cetylpyridinium chloride in three commercial root canal sealers. Materials and Methods: Three different root canal sealers were used: EndoRez, N2, and Apexit Plus. The samples were prepared by mixing the components according to the manufacturers’ guidelines and adding 2% in weight of the antimicrobials to the newly mixed cement. The paste was placed in molds and stored in an incubator (37°C, 24 h). The samples were then stored in 5-mL distilled water. Samples without antimicrobials served as a control. All samples were tested at 3 time intervals: 1 day, 1 week, and 1 month following their storage in distilled water. The impact of the antimicrobials on the solubility of the sealers, the release of chloride ions (Cl—), and the pH value were examined. Statistical Analysis Used: Analysis was done using one-way analysis of variance and the post hoc Tukey's honestly significant difference test. Results: Chloride ions are present in storage media with EndoRez, N2, and Apexit Plus samples (without antimicrobials) following all tested storage intervals. The addition of the antimicrobials increased the release of chloride ions. Endodontic cements without addition of antimicrobials show an increase in weight after 1 month. The highest pH value is measured in Apexit Plus samples. The solutions in which N2 samples (with and without addition of antimicrobials) were stored did not have a significant change in their pH, while in the EndoRez solutions, a significant decrease in the pH value after the first week was measured. Conclusions: The addition of antimicrobials might lead to improved characteristics of the root canal sealers

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

[Background and Aims]: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression. [Methods]: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5+/–;Kras), and compared them with mice with only oncogenic Kras (controls). Pancreata were analyzed by histology and immunohistochemistry. Primary tumor cells were isolated and used to perform transcriptome, metabolome, intracellular calcium, extracellular cathepsin activity, and cell migration and invasion analyses. The cells were injected into wild-type littermates, and orthotopic tumor growth and metastasis were monitored. Atg5 was knocked down in pancreatic cancer cell lines using small hairpin RNAs; cell migration and invasion were measured, and cells were injected into wild-type littermates. PDAC samples were obtained from independent cohorts of patients and protein levels were measured on immunoblot and immunohistochemistry; we tested the correlation of protein levels with metastasis and patient survival times. [Results]: A5+/–;Kras mice, with reduced Atg5 levels, developed more tumors and metastases, than control mice, whereas A5;Kras mice did not develop any tumors. Cultured A5+/–;Kras primary tumor cells were resistant to induction and inhibition of autophagy, had altered mitochondrial morphology, compromised mitochondrial function, changes in intracellular Ca2+ oscillations, and increased activity of extracellular cathepsin L and D. The tumors that formed in A5+/–;Kras mice contained greater numbers of type 2 macrophages than control mice, and primary A5+/–;Kras tumor cells had up-regulated expression of cytokines that regulate macrophage chemoattraction and differentiation into M2 macrophage. Knockdown of Atg5 in pancreatic cancer cell lines increased their migratory and invasive capabilities, and formation of metastases following injection into mice. In human PDAC samples, lower levels of ATG5 associated with tumor metastasis and shorter survival time. [Conclusions]: In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells.This study was supported in part by the Mildred-Scheel-Professur der Deutschen Krebshilfe 111464, DFG AL 1174/6-1 to H.A., DFG DI 2299/1-1 to K.N.D., DFG SFB1321 (S01) to K.S. and W.W., and the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD e.V.) to J.A

a review of methodological design choices

Publisher Copyright: © 2023 Cambridge University Press. All rights reserved.This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the Disability-Adjusted Life Years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3,053 studies of which 2,948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.publishersversionepub_ahead_of_prin

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results

Association between dental caries risk indicators and various stages of caries in newly erupted permanent teeth

Background/Aim. Identification of caries risk indicators involved in the disease development is of great importance. The aim of this study was to assess the association between distinctive risk indicators and different stages of caries disease process in children. Methods. The cross-sectional study was conducted on a sample (n = 327) of school children ages 7–11. A questionnaire submitted to parents was used to record the data regarding demographic characteristics, children's dietary habits, oral hygiene habits and oral health behaviors. Caries was assessed using the International Caries Detection and Assessment System (ICDAS) II and subjects were stratified according to the highest and most prevalent caries lesion stage. The data obtained were analyzed using the χ2 or Fisher`s exact test and multinomial logistic regression. Results. Caries lesions were detected in 56.6% of examinees observed in the study. Compared to caries-free subjects, appearance of initial caries lesions was statistically significantly influenced by maternal education level (p = 0.021), paternal occupational status (p = 0.023), toothbrushing frequency (p < 0.001), and caries status of deciduous teeth (p = 0.027). Maternal educational level (p = 0.026), paternal occupational status (p = 0.003), sweets and snacks taking frequency (p = 0.005), toothbrushing frequency (p < 0.001), and fluoridate dentifrice usage (p = 0.027) were associated with moderate caries lesions. Maternal educational level (p < 0.001), sweets and snacks taking frequency (p = 0.022) and toothbrushing frequency (p < 0.001) were associated with extensive caries lesions. Maternal educational level (p = 0.02) and brushing frequency (p < 0.001) were statistically significantly associated with the highest prevalence of initial caries lesions. Maternal educational level (p = 0.025), toothbrushing frequency (p < 0.001) and frequency of dental check-ups (p = 0.016) were statistically significantly associated with the highest prevalence of moderate caries lesions. Conclusion. Parental socioeconomic indicators and children's behavior related to oral health were involved in the changes from caries-free status to different caries stages

Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response

Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2− levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation

Reliability and Versatility of Reverse Sural Island Neurofasciocutaneous Leg Flaps

BACKGROUND Distally based sural neurofasciocutaneous (NFC) flaps are a commonly used method for foot and ankle reconstruction given that they are much simpler and, at the same time, still efficient alternative to perforator flaps and free style free flaps. OBJECTIVE This study aims to evaluate the reliability and versatility of reverse sural island NFC flaps as a powerful and efficient method that can be used for repair of lower leg skin defects. This method does not require microsurgical facilities or extensive training. METHODOLOGY Patients with soft tissue defects of the distal third of the leg and ankle region received reverse sural island NFC flaps. Inclusion criteria included an absence of damage to the sural neurovascular axis or communicating perforators, absence of peripheral vascular disease, and the presence of soft tissue defects deep enough to expose tendon or bone. Patients were assessed for flap (defect) size, pedicle length and location of defects, postoperative flap survival rates, and complications. Donor sites were closed directly or skin grafted. RESULTS Of 24 consecutive patient (20 male; 4 female), all flaps except 1 (4.16%), survived, although partial necrosis was observed in 2 patients (8.33%). The overall major complication rate was 12.50%. Epidermolysis was noted in 1 patient (4.16%). Three cases of transient venous congestion resolved without additional complications. The overall minor complication rate was 16.66%. Minimal complications were associated with healing of donor sites. CONCLUSIONS Reverse sural island NFC flaps provide adequate and aesthetically very acceptable coverage of soft tissue defects of the distal lower leg and proximal foot with no functional impairment

Unacylated ghrelin suppresses grelin-induced neuronal activity in the hypothalamus and brainstem of male rats

Ghrelin, the endogenous growth hormone secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and unacylated (UAG). Many studies suggest different roles for these two forms of ghrelin in energy balance regulation. In the present study, we compared the effects of acute intracerebroventricular administration of AG, UAG and their combination (AG+UAG) to young adult Wistar rats on food intake and central melanocortin system modulation. Although UAG did not affect food intake it significantly increased the number of c-Fos positive neurons in the arcuate (ARC), paraventricular (PVN) and solitary tract (NTS) nuclei. In contrast, UAG suppressed AG-induced neuronal activity in PVN and NTS. Central UAG also modulated hypothalamic expression of Mc4r and Bmp8b, which were increased and Mc3r, Pomc, Agrp and Ucp2, which were decreased. Finally, UAG, AG and combination treatments caused activation of c-Fos in POMC expressing neurons in the arcuate, substantiating a physiologic effect of these peptides on the central melanocortin system. Together, these results demonstrate that UAG can act directly to increase neuronal activity in the hypothalamus and is able to counteract AG-induced neuronal activity in the PVN and NTS. UAG also modulates expression of members of the melanocortin signaling system in the hypothalamus. In the absence of an effect on energy intake, these findings indicate that UAG could affect energy homeostasis by modulation of the central melanocortin system