Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Although researchers have proposed various indentation size effect (ISE) models, these models often involve different form and number of parameters that can make our wonder which is the best in existed ISE models. Three types of ISE test data, namely, normal ISE, reverse ISE and transition of normal to reverse ISE, are used to evaluate the sixteen ISE models. The comparatively study indicates that H-J, N-G-Fs, N-G-H, N-G-A and N-G-Qs models can accurately predict the normal ISE. The reason for this is that the friction stress that is not related to dislocation activities or the indentation size effect of plastic zone has been introduced into these models. Therefore, these two factors should be considered in future ISE models. The sixteen ISE models are originally proposed to describe the normal ISE of different materials. However, to our surprise, some of these models are able to capture the reverse ISE and the transition of normal to reverse ISE of different materials. The determination coefficients (DC) of the sixteen ISE models are also determined for different materials. For reverse ISE, the highest DC value for NiCSi, TC4 and PED Ni are given by the EXP, N-G-Fs and N-G-A models, respectively. For the transition of normal to reverse ISE, the N-G-YC, N-G-Fs, and N-G-H models produce the maximum DC for ZrO2, Cu and Y2O3-ZrO2, respectively. Moreover, the mean DC of the N-G-Fs model is the maximum among the sixteen ISE models, followed by the N-G-H model, but they cannot accurately predict the reverse ISE. Therefore, the N-G-Fs and N-G-H models should be further modified to accurately predict the reverse ISE.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P<0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P>0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P<0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P<0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p<0.05; p<0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p<0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

The aim of this study was to evaluate the effect of two different insertion speeds at 8 different insertion torque values ranging from 25-60 during implantation in a dense polyurethane D1 bone model on the placement status and removal torque of dental implants. In this study, 50 pcf single layer polyurethane plates were used. In the study, a total of 320 implant sockets were divided into 2 groups as Group 1 (30 rpm) and Group 2 (50 rpm) in terms of insertion speed. Group 1 and Group 2 were divided into 8 subgroups as 25, 30, 35, 40, 45, 50, 55 and 60 torques. There were 20 implant sockets in each subgroup. During the implantations, implant placement status and removal torque values were assessed. There was a statistically significant difference between the 30 and 50 RPM groups in terms of overall implant placement status (p<0.01). It was found that the removal torque values at 50 RPM were statistically significantly higher than those at 30 RPM (p<0.01). This study showed that in dense D1 bone, the minimum parameters at which all implants could be placed at bone level were 50 torque at 30 rpm and 40 torque at 50 rpm.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

Introduction: Oral Nicotine Pouches (ONPs) are the new form of nicotine pouches that have become a type of emerging smokeless tobacco product sold by various tobacco companies. These smokeless tobacco products are being marketed for usage all over as Snus containing tobacco-derived nicotine (Natural) or as tobacco-free nicotine (Synthetic) as substitutes for other tobacco products that are limited in public places. ONPs have become popular tobacco products among adolescents/young adults and over 50% of young adult users of ONP use flavored ONP, such as menthol/mint, tobacco, dessert/candy, and fruity, being the most popular flavors. Various new ONP flavors are currently popular locally as well in the online market. Tobacco, Menthol, and fruit-flavored ONPs could motivate cigarette smokers to alteration to ONPs. Methods: We expanded our knowledge on natural/synthetic ONP flavors wheels to available data on ONPs, describing in detail their flavors and brands (US and Europe) in both natural/Synthetic ONP categories. We classified over 152 snus and 228 synthetic ONPs into the following flavor categories: “Tobacco”, “Menthol/Mint”, “Fruity”, “Candy/Deserts”, “Drink”, “Aroma”, “Spices” and “Mixed Flavors”. Results: Based on total numbers, wefound that the most popular ONPs flavor sold as tobacco and menthol to be among natural ONPs, among synthetic ONPs fruity and menthol as the most prominent flavors with varying concentrations of nicotine and other flavoring chemicals including coolant WS-23. We also illustrated possible molecular targets and toxicities due to exposure to ONPs activating several signaling cascades like AKT and NF-B might possibly lead to apoptosis and epithelial mesenchymal transition (EMT). Conclusions: Considering the marketing of ONP products with various flavor profiles and most of these products containing tobacco/menthol/fruit flavor, it is likely to have regulation and marketing disclaimer on some of these products. Further, it would be logical to determine how the market reacts in terms of compliance and non-compliance with flavor restrictions by the regulatory agencies.

Background: Pancreatic neuroendocrine tumors (pNETs) represents a rare subset of pancreatic cancer. Functional tumors caused hormonal changes and clinical syndromes, while non-functional ones are often diagnosed late. Surgical management need a multidisciplinary planning, involving enucleation, distal pancreatectomy with or without spleen preserving, cen-tral pancreatectomy, pancreaticoduodectomy or total pancreatectomy. Minimally invasive ap-proach increased in the last decade compared to the open technique. The aim of this study is to analyze current diagnostic and surgical trends for pNETs, to identify better interventions and their outcomes. Methods: The study adhered to PRISMA guidelines, conducting a systematic review of literature from May 2008 to March 2022 across multiple databases. Several combinations of keywords was used ("NET", "pancreatic", "surgery", "laparoscopic", "minimally invasive", "robotic”, “enuclea-tion”,“parenchima sparing”) and relevant article references was manually checked. Manuscript quality was evaluated. Results: The study screened 3867 manuscripts, twelve studies were selected, primarily from Ita-ly, the United States, and China. A total of 7767 surgical treated patients was collected from 160 included centers. The mean age was 56,3 y.o. Enucleations (EN) and distal pancreatectomy (DP) was the most common performed surgery and represents 43.4% and 38.6% of the total interven-tions, respectively. Pancreatic fistula, post operative bleeding, re-operation and follow up was recorded and analyzed. Conclusions: Enucleation show better postoperative outcomes and lower mortality rates com-pared to pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), despite similar risks of postoperative pancreatic fistula (POPF). DP was preferred over enucleation for pancreas body-tail, while laparoscopic enucleation is better for head pNETs.

Researchers have asserted that, as patients rely on external powerful sources to control their disorders, in addition to their own internal powers and virtues, examining their coping mechanisms can lead to a better understanding of the initiation and progression of chronic diseases and uncover potential opportunities to balance and enhance their psycho-spiritual well-being and possibly their treatment and recovery. This review serves as a user’s manual for investigators who choose to use the CSI-SF to conduct their research on coping behaviors. The CSI-SF that measures four coping strategies based on 16 items was first assessed using the Jackson Heart Study (JHS) cohort in 2007. The reliability and construct validity of the CSI-SF was also later assessed among hemodialysis patients across 13 countries. In this study, the CSI-SF was assessed to be a reliable and valid instrument for measuring coping strategies. The CSI-SF serves the purpose of developing an inner voice that can assist with understanding how people cope with everyday life. The information gathered from administration of the CSI-SF can inform investigators about environmental cues and triggers that can also impact individual health.

Solvents are widely-used in all aspects of chemical sciences. One of the disadvantages of conventional solvents is attributed to the adverse impacts they pose on human health and ecological systems. Emerging class of solvents such as ionic liquids have been proposed to alleviate this problem. In this study, aquatic toxicity and biodegradability of two common industrial solvents are compared to those of two ionic liquids. Results from this study highlight the importance of solvent selection considering the information on the toxicity, biodegradability and fate and transport properties of selected solvents altogether.

Keywords: Oral health, diabetes, periodontal disease, caries, periodontitis.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p < 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Vertical and horizontal bone augmentation is one of the most challenging techniques in bone engineering. The use of barrier membranes and scaffolds in guided bone regeneration (GBR) procedures is a common approach for the treatment of lost bone around teeth and dental implants. The aim of this study was to estimate the barrier effects of a synthetic poly (lactic acid/caprolactone) [P(PA/CL)] bilayer membrane for GBR, compared to a porcine collagen bilayer membrane, in the vertical augmentation model on 10–12-months old rat skull without periosteum. The HAp block (diameter: 4 mm, height: 3 mm, porosity:75%, average pore size:150 μm) was placed on the rat skull without a periosteum. The P(LA/CL) membrane (solid layer: 25 μm, porous layer: 175 μm) or the collagen membrane (solid layer, porous layer) was applied onto the HAp block. At 3, 6, and 12 weeks after the surgery, the incised tissues were fixed, decalcified, and stained with hematoxylin and eosin for histological evaluation. The P(LA/CL) membrane remained until 12 weeks and could achieve barrier effects to inhibit cellular invasion from the repositioned soft tissues. Local bone formation occurred in the interconnected pores of HAp at 6 weeks. On the other hand, the collagen membrane did not inhibit cellular invasion for its expansion until 3 weeks, and was absorbed until 6 weeks. The results indicated that the P(LA/CL) membrane might be effective in GBR as occlusive absorbable membrane.

Background: Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delay leading to worse outcomes and decreased quality of life. Therefore, there is an urgent need for an approach to predict normal mucosa response in patients prior to treatment. Methods: We here describe an assay to detect irradiation response in patient healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated, and cultured for three days. Seven samples were irradiated with X-ray and three additional samples were irradiated with both X-ray and protons. Results: Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample, using standardized automated image analysis. Furthermore, increased levels of inflammation inducing factors - major drivers in mucositis development - could be detected after irradiation. Conclusion: This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

(1) Background: Tooth extraction is one of the oldest and most well-known surgical procedures in dental medicine. It is still routinely performed to date by both general practitioners, oral surgeons, and dental undergraduates. The Benex extraction system allows for the extraction of teeth in vertical direction, which avoids most trauma against the surrounding alveolar bone and soft tissues; (2) Methods: The study included 56 patients who were recruited from the department of Oral Surgery at the Faculty of Dental Medicine, Medical University – Plovdiv. Patients were divided into two groups of 28 patients – Group I (control group) and Group II (study group). For each group the success of the extraction, buccal cortical plate preservation, pain experience and early wound healing were assessed; (3) Results: There was no statistical significance between the success of the extractions in both groups. The Benex extractions preserved the buccal cortical plate in 95% of the cases, whereas the forceps extractions only in 71.8%, which shows a statistical significance. On the seventh day patients in group II reported less pain, without a significant difference. There was a significantly bigger number of completely healed extraction wounds on the 10th day; (4) Conclusions: Atraumatic extractions allow for more hard and soft tissues to be preserved in the extraction site. This is all crucial for the successful outcome and aesthetically pleasing results of a following prosthetic or implant restoration.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Space-based gravitational wave detection is extremely sensitive to disturbances. The Keplerian configuration cannot accurately reflect the variations in spacecraft configuration. Planetary gravitational disturbances are one of the main sources. Numerical simulation is an effective method to investigate the impact of perturbation on spacecraft orbits. This study shows that, in the context of the Taiji project, Earth’s gravity is an essential factor in the change in heliocentric formation configuration, contributing to the relative acceleration between spacecrafts in the order of O(10−6)m·s−2. Considering 00:00:00 on October 27, 2032 as the initial orbiting moment, under the influence of Earth’s gravitational perturbation, the maximum relative change in armlengths and variation rates of armlengths for Taiji is 1.6×105km, 32m·s−1 respectively, compared with the unperturbed Keplerian orbit. Additionally, by considering the gravitational perturbations of Venus and Jupiter, the armlength and relative velocity for Taiji are reduced by 16.01% and 17.45%, respectively, compared with when only considering that of Earth. The maximum amplitude of the formation motion indicator changes with the orbit entry time. Results show that the relative velocity increase between the spacecrafts is minimal when the initial orbital moment occurs in July. Moreover, the numerical simulation results are inconsistent when using different ephemerises. The differences between ephemeris DE440 and DE430 are smaller than those between DE440 and DE421.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

Resection of malignant lesions in the oral and maxillofacial area causes functional and morphological defects. To recover from these defects, reconstruction surgery is needed such as a primary closure or a flap. There are advantages and disadvantages to the method of using the primary closure and the flap, and the choice of procedure is entirely up to a surgeon. The purpose of this study is to evaluate availability of primary closure in patients. For 10 years from January 2010 to May 2020, patients who recovered using flaps after removing malignant lesions from the oral cavity and those who closed the lesion using primary closure were investigated. The investigation was conducted by searching the database of the hospital. There were 85 patients who removed malignant lesions in the oral and maxillofacial area, and among them 16 patients closed the soft tissue defects using primary closure. Operation time, histologic types, stages, wound status, and period of hospitalization according to the patients' medical records were investigated retrospectively. Between the staging and the primary closure, statistically significant differences were observed between stage I and stage II patients in 13 patients using the primary closure. (P=0.046). Statistically significant differences were identified between operation time and primary closure, with an average of 4.02 hours (P=0.015). The average period of hospitality for patients who underwent primary closure was 13.4 days, compared to 26.7 days for those who underwent flap surgery. This difference was statistically significant (P=0.0003). This study evaluated the use of primary closure in patients who underwent resection of malignant lesions in the oral and maxillofacial area. Although the majority of patients underwent reconstruction with flaps, our results showed that primary closure can be a viable option for certain patients with early-stage lesions. Therefore, oral and maxillofacial surgeons should carefully consider various evaluation criteria and select appropriate reconstruction methods to optimize functional and aesthetic outcomes for each patient.

Dental agenesis is one of the most common developmental anomaly in humans and it is frequently as-sociated with several other oral abnormalities. The present case describes nonfamilial agenesis of per-manent teeth in a twenty-one-year-old boy, with no apparent systemic abnormalities. The treatment in-cluded a personalized and interdisciplinary approach by the means of endodontics, orthodontics, im-plants supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing, and mock-up previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants, and monolithic Zirconia implant supported restorations. The final results showed a highly aesthetic and functional rehabilitation. Periodic checkups have shown that the stability of the result is well maintained and that the implant supported restorations are an op-timal solution for patients with multiple anodontia.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Phthalates are esters of Pthalic acid, compounds mainly used as plasticisers. Phthalates are widely used chemicals which are of significant research interest as their exposure causes various consequences for human health. There are several categories of phthalates extensively used in many commercial productions with diverse uses, physicochemical properties and toxicological effects. This chapter discusses the toxicity of Phthalates and its potential risks to human health.

Oral health involves physiological functions related to mouth, teeth and orofacial structures, but also includes psychological and social dimensions. In this sense, oral health is an integrated part of human general health and well-being. Our aim was to access and evaluate the general oral health status of a high- and elite-level sample of Portuguese athletes from different sports. One hundred and sixteen participants were examined regarding their dental relationships, teeth and periodontal health, the presence of parafunctional activities (bruxism), and current or past orthodontic treatment. Our sample were predominantly adolescents and young adults, including 54 high-level and 62 elite subjects (71 males and 45 males) from 11 different sports, but mainly from swimming and athletics. Most sport performers presented with normocclusion (77%), despite the presence of other sagittal, transverse and vertical malocclusions. Twenty-three participants were affected by dental caries and six had missing teeth. Gingivitis (~40%) and dental calculus (~30%) were presented in our sample. Bruxism signs (47%) and current or past orthodontic treatment (~22%) were also found. Oral health conditions are not under control among high- and elite-level athletes, supporting the importance of healthcare needs and oral health promotion strategies in sports.

Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated dose toxicity of Hu7691 in male and female Sprague-Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg, while female rats received doses of 12.5, 25, 50, and 75 mg/kg for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg, while for female animals, it should be less than 50 mg/kg.

Background: Patients with thromboembolic disease, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Although common professional oral hygiene might not represent a health concern for these patients, anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to investigate the bleeding time of different anticoagulants and antiplatelets during a professional hygiene session adapting the Ivy test to the oral environment; Methods: 93 consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn’s post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; Results: Control patients presented the lowest bleeding time 50 sec, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p=0.004), VKA (p&lt;0.001), DAPT (p&lt;0.001). Conclusions: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. However, bleeding did not interfere with the oral hygiene ses-sion The optimal period for dental treatment of these patients should be 2-3 hours before the next dose, without the need to temporarily suspend the medication.

This work explores the significance of toothbrushing in maintaining optimal oral health, delving into its benefits, proper techniques, and types of toothbrushes. The primary cause of caries, periodontal diseases, and halitosis is oral biofilm development. One of the most fundamental practices in maintaining oral health is toothbrushing. Studies have confirmed that mechanical procedures for controlling plaque and toothbrushing, in particular, significantly decrease plaque accumulation. The significance of teeth brushing in preventing dental caries has been well-acknowledged for a considerable period. Dentists recommend brushing twice daily for at least two min to ensure thorough cleaning. Unfortunately, precise guidelines from dental associations are often missing. Authors mention that two min of brushing are insufficient for significant plaque removal; plaque removal increases with augmented brushing time, with maximum removal at 180 s. Multiple studies have documented that engaging in the practice of brushing one’s teeth twice a day has a preventive impact. Various toothbrush designs, including both manual and electric options, have been created to improve the elimination of dental biofilm and reduce the accumulation and persistence of bacteria. In conclusion, toothbrushing is a simple yet incredibly important practice for maintaining oral health. The benefits extend beyond just a bright smile, encompassing caries, gum disease, halitosis prevention, and the preservation of tooth enamel. Adhering to proper toothbrushing techniques, selecting the right toothbrush, and understanding the connection between oral health and overall well-being can lead to a healthier life. To foster favorable toothbrushing behaviors among the population, dental practitioners and public health experts must know the factors that influence toothbrushing habits.

Background: Research articles are essential for describing new ideas, techniques, and procedures and consolidating concepts. It creates an opportunity to expose studies and publicly assimilate published knowledge. Therefore, one of them is the most used and accepted index to verify the author’s scientific impact is the H-index or Hirsch index. It provides a robust single metric that combines quality and quantity. Therefore, it presents disadvantages, (1) researchers with shorter scientific carriers may have fewer articles and citations than those with longer scientific life; (2) it allows scientists to receive citations even if no new papers are published; (3) it is only useful for comparing the better scientists in a field; (4) this indicator can never decrease; (5) it is only weakly sensitive to the number of citations received; (6) the major and minor (or no) contributor in the research gained equal h-index. Then, the H-index ignores the total of citations and the time of a researcher's experience (“scientific age” [sa]). Objective: Thus, the goal of this study was to present a new index system (GFsa index ©) based on the two variables completely forgotten (total of citations and “scientific age”), introducing a new terminology “scientific age”, to evaluate the best-ranked researchers in Dentistry. Methods: The AD Scientific Index was used, and all researchers included in this study were cited in the AD Scientific Index (2024) in the Dentistry field and had the Google Scholar page accessible for a consultation to manually obtain the total of citations and calculate the “scientific age”. The information was retrieved by two authors (G.V.O.F. and J.C.H.F.), who assessed the data twice to avoid errors or mistakes. For inclusion: a minimum H-index value of 30; for exclusion: (i) the author did not have a Google Scholar page; (ii) duplicated author; or (iii) presented any suspicious activities about manipulation of articles. Then, a dataset of all researchers who were reported in Dentistry was prepared (name, H-index, i10 index, and publications). The formula developed and applied was GFsa=(total number of citations)/(“scientific age)². The Pearson correlation statistically evaluated the data obtained; the confidence interval was 95%. Results: A total of 9,093 researchers in Dentistry were recorded, of whom 1,020 were included. Then, we collected all 1,020 researchers' Google Scholar data (publications, citations, and indexes), and each researcher's total citations and “scientific age” were registered and calculated. The mean “scientific age” registered was 34.18 ± 13.34 (standard error of mean = 0.4181). With this information and data collected, GFsa index © was calculated, presenting a minimum value of 0.2186 and a maximum of 154.8 (mean = 10.33 ± 11.82; standard error of mean = 0.3706). Then, the data was organized and sorted following the ranking obtained in the GFsa index ©. The Pearson correlation showed that the H-index had a weakly positive association with the researcher’s “scientific age”; this fact means that the H-index will increase according to the “scientific age” increase. Otherwise, a moderately negative correlation between GFsa and “scientific age” was demonstrated, whereby a higher GFsa © had a lower “Scientific age”. This assessment shows that the variables introduced were fairly used. Moreover, a positive correlation was observed between both indexes (H-index and GFsa). Conclusion: It is possible to conclude that the new variable reported (“Scientific age”) and using the total citations brought a fairer and more feasible evaluation among the researchers. Thus, we are launching the new GFsa index © and the new information named “Scientific age” for the first time in the literature. The future perspective of the GFsa © application will be (1) the evaluation of the 9,093 researchers in Dentistry (total initially registered), including more authors/researchers in the Dentistry field, (2) expanding the exposition of this new index for other areas of the knowledge, and (3) provide free access of all data through the website (http://gfindex.us.to).

The oral microbiome is a diverse and complex ecosystem essential for maintaining oral and systemic health. Our study is the first to define the oral microbial community in Egyptian young adults and investigate the effects of natural antimicrobials on the oral microbiome. SuperMint (SM) is a proprietary blend of peppermint, Japanese mint, bergamot mint, and spearmint essential oils encapsulated in a tiny soft beadlet. This work aimed to evaluate the effects of SM beadlets on the oral microbiome. This study recruited twenty healthy participants. A baseline investigation of the oral microbiome of the selected participants was performed by collecting saliva and swab samples before treatment. Treatment included chewing four SM beadlets twice a day for 7 days, and then post-administration saliva and swab samples were collected at the end of treatment. The oral microbiome samples were analyzed by high-throughput amplicon sequencing of 16S rRNA gene fragments, and the community composition was determined. The results showed that the abundance of some microbial genera and families decreased after using SM, including Prevotella, Streptococcus, Neisseria, and Haemophilus. However, some genera showed inconsistent patterns. We also found that the subject's gender and SM usage were significantly associated with diverse microbial composition. The results suggest that SM treatment decreased the abundance of several bacteria associated with halitosis and periodontal diseases, such as Actinomyces and Streptococcus. Furthermore, Corynebacterium species increased while Streptococcus decreased after SM usage. More research is needed to fully understand the antimicrobial effects of mint oils and their potential applications in maintaining good oral health.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is a suitable environment that provides various kinds of biological niches such as teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome plays an important role in triggering, development, and progression of oral and systemic diseases. Currently, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology, and is overwhelmingly promising compared to the previous era. It has been found that patients with oral diseases and systemic diseases have variations in the oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that oral microbiome plays in influencing oral and systemic diseases, and updates the knowledge related to the oral microbiome over the past 30 years. A wide range of updates was provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and help develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

Background Gingivitis can develop without mechanical cleaning within three weeks. The first clinical sign is bleeding on positive probing. The accumulation of dental biofilm generates an inflammatory gingival response. In the past decade, attention has focused mainly on the interproximal areas and the use of customsized interproximal toothbrushes.The aim of the study was to evaluate the effectiveness of individualized oral hygiene education and its role in dental prevention among patients with dental problems. Methods Before treatment, patients were clinically and radiologically examined, full mouth plaque score (FMPS), full mouth bleeding score (FMBS), and bleeding on brushing (BOB) were recorded, and matrix-metalloproteinase-8 (MMP-8) was measured by using a chair-side MMP-8 measuring system. Patients in group A had gingivitis, but no periodontal damage and patients in group B had periodontal damage. Patients in both groups A and B were identified in to four subgroups based on their toothbrushing habits and the oral health education they received. The three months after initial examination, each patient was examined three more times (2, 4 and 12 weeks later). Results It was concluded that subjects in groups A1 and B1 showed significant reduction in BOB, MMP-8, FMBS and FMPS levels after two weeks. Solo Prophylaxis (A1and B1) remained as a well-constructed protocol with hte complete resolution of interdental inflammation after two weeks. Other subgroups achieved significant reductions only after 12 weeks. Conclusions BOB and MMP-8 are valuable complements in preventive dentistry, and are able to detect potential pathological processes in interproximal spaces. The clinical relevance of BOB, in addition to FMBS, FMPS and gingival inflammation can be demonstrated to patients, which may increase compliance.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

The EPA has banned PFOA and PFOS as persistent organic pollutants, but their residues in environment should not be underestimated. Based on the demand for healthy aquaculture and safe aquatic products, it is necessary to explore alleviative methods for the toxicity of PFOA and PFOS to fish. This study is the first to investigate the protective effects of Lactobacillus rhamnosus against oxidative damage, neurotoxicity, and gut microbial dysbiosis induced by PFOA and PFOS in adult zebrafish. The results showed that L. rhamnosus effectively alleviated PFOA- and PFOS-induced oxidative stress by restoring superoxide dismutase (SOD), catalase (CAT), and lactate dehydrogenase (LDH) levels. Both PFOA and PFOS caused intestinal tissue damage, and the degree of damage is PFOA+PFOS>PFOS>PFOA. L. rhamnosus can restore damaged intestinal villi and lymphocyte numbers and also have a restorative effect on intestinal tissue damage. The up-regulated proportion of beneficial Firmicutes and Actinobacteria was also found after L. rhamnosus feeding. These findings provide new insights for L. rhamnosus to alleviate the toxicity of PFOA and PFOS to zebrafish and promote the progress of research on the successful use of probiotics in freshwater aquaculture.

Abstract: Purpose of review: This review investigates the oral microbiome's composition, functions, influencing factors, connections to oral and systemic diseases, and personalised oral care strategies. Recent findings: The oral microbiome is a complex ecosystem consisting of bacteria, fungi, archaea, and viruses that contribute to oral health. Various factors, such as diet, smoking, alcohol consumption, lifestyle choices, and medical conditions, can affect the balance of the oral microbiome and lead to dysbiosis, which can result in oral health issues like dental caries, gingivitis, periodontitis, oral candidiasis, and halitosis. Importantly, our review explores novel associations between the oral microbiome and systemic diseases including gastrointestinal, cardiovascular, endocrinal, neurological conditions, autoimmune diseases, and cancer. We comprehensively review the efficacy of interventions like dental probiotics, xylitol, oral rinses, fluoride, essential oils, oil pulling, and peptides in promoting oral health by modulating the oral microbiome. Summary: This review emphasizes the critical functions of the oral microbiota in dental and overall health, providing insights into the effects of microbial imbalances on various diseases. It underlines the significant connection between the oral microbiota and general health. Furthermore, it explores the advantages of probiotics and other dental care ingredients in promoting oral health and addressing common oral issues, offering a comprehensive strategy for personalized oral care.

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

On Feb. 6^th, 2020, FDA implemented the enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products’ attraction to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and re-established attractions. Both the sales of e-cigarettes and posts on social media suggested that the manufacturers’ strategies are likely “successful”. The re-established attraction causes not only a public health issue, but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes that are likely added in tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco free nicotine, and these other flavors are associated with higher clinical symptoms not often induced by only natural traditional tobacco flavors. The additional health risks posed by the flavorants are pronounced even without considering the interactions of toxicology of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for regulation of these emerging products.

Food production is a complex matter, affecting people’s lives, organizations’ profits, and the well-being of the whole planet and has multifaceted ethical considerations surrounding its production, distribution, and consumption. This paper addresses the pressing need to confront ethical challenges within the food system, encompassing issues such as environmental sustainability, food security, and individual food choices for better oral and systemic health of all individuals around the globe. From agricultural practices to global trade and food waste, ethical implications are addressed across various domains, highlighting the interconnectedness of ethical decision-making in the food industry. Central themes explored include the ethical dimensions of food production methods, the impact of global trade on food ethics, and the role of individuals in making ethically informed food choices. Additionally, the paper dives into the spiritual and physical significance of food, particularly through the lens of oral health as a gateway to holistic well-being. Recognizing the complexity of the food ecosystem, the paper calls for serious interventions in legislation and economics to promote ethical protocols and techniques for sustainability reasons. It emphasizes the importance of ethical considerations in food safety management systems, regulatory frameworks, and quality standards. Moreover, the paper underscores the need for a comprehensive approach to address ethical dilemmas and moral values inherent in the food industry and oral health policies, advocating for the adoption of the precautionary principle and ethical decision-making frameworks. The article aims to serve as a call to action for stakeholders across the food industry and the healthcare sector, to prioritize ethical practices, promote transparency, rearrange economic parameters and work towards a more sustainable and equitable food system for inner and outer oral and systemic health and human sustainability for all.

Fifty-eight Karacabey Merino lambs were used to evaluate the effects of feeding system (triticale pasture, oat pasture, or stall fed), birth type (single or multiple), gender (male or female) and birth year (2016 or 2017) on various carcass and meat quality characteristics. Stall lambs had higher conformation (CS) and fatness scores (FS), meat L* and h* values than both pasture groups, possibly as a result of higher fat content, while oat pasture lambs had the most tender meat. Single lambs had higher CS, FS and Longissimus thoracis muscle section area, while females had higher subcutaneous and non-carcass fat depositions, over their counterparts. Both single born lambs and 2016 born lambs had a higher meat a* and C* values than their counterparts. In conclusion, a pasture-based feeding system is thought to be more suitable for Karacabey Merino than stall feeding system, for those who prefer leaner meat and/or meat products. However, it should not be ignored that stall fed lambs showed a better fattening performance in terms of conformation and fatness, in the same period.

Background: To compare photodynamic therapy 41 and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. Methods: Participants aged from 18 to 25 years, showing sulfide (SH2) ≥ 112 ppb on gas chromatography, were selected. They were divided into 4 treatment groups: Group 1 - Tongue Scraping; Group 2- Antimicrobial Photodynamic Therapy (aPDT); Group 3- Probiotics; Group 4- Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, 7 days, 14 days and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry, for the microbiome analysis. Results: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. Conclusions: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.

This study evaluated the influence of methotrexate (MTX) and non-surgical periodontal treatment (NSPT) on the composition of the oral-gut microbiota in patients with rheumatoid arthritis (RA). Assessments were performed at baseline (T0), 6 months after MTX treatment (T1), and 45 days after NSPT (T2). The composition of the oral and gut microbiota was assessed by amplifying the V4 region of the 16S gene from subgingival plaques and stools. The results of the analysis of continuous variables were presented descriptively and non-parametric tests were adopted. Thirty-seven patients (27 with periodontitis) were evaluated at T0; 32 patients (24 with periodontitis) at T1; and 28 patients (17 with periodontitis) at T2. Nine individuals were lost to follow-up. MTX tended to reduce the alpha diversity of the oral-gut microbiota, while NSPT appeared to increase the number of different species of oral microbiota. MTX and NSPT influenced beta diversity in the oral microbiota. The relative abundance of oral microbiota was directly influenced by periodontal status. MTX did not affect the periodontal condition but modified the interactions between clinical parameters and the oral-gut microbiota. MTX and NSPT directly affected the composition and richness of the oral-gut microbiota. However, MTX did not influence periodontal clinical parameters.

Breadfruit [Artocarpus altilis (Parkinson) Fosberg] is recognized as a tropical fruit tree crop with great potential to contribute to food and nutrition security in the Caribbean and other tropical regions. However, the genetic diversity and identification of germplasm in the Caribbean and elsewhere is not well understood and documented. This hampers the effective conservation and use of the genetic resources of the tree crop for commercial activities. This study assessed the genetic identity, diversity, ancestry, and phylogeny of breadfruit germplasm existing in Caribbean and recently introduced accessions using 117 SNPs from 10 SSR amplicon sequences. The results showed that there was high genetic diversity in the breadfruit germplasm in the Caribbean, as well as the newly introduced breadfruit accessions based on nucleotide diversity (π_T) and nucleotide polymorphism (θ_W). Furthermore, based on these measures of genetic diversity, there were no significant differences between existing Caribbean breadfruit accessions and newly introduced breadfruit accessions which are known to be highly diverse. Ancestry and phylogeny analysis corroborated the genetic relatedness of these two groups with accessions of these groups being present in both main germplasm clusters. This suggests that the existing Caribbean breadfruit germplasm harbors a higher level of genetic diversity than expected.

Background: The leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria because of the numerous nutritional and medicinal attributes ascribed to it. The sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was investigated in this study. Methods: Rats in different groups were separately administered 80, 400 and 2000 mg/kg TO p.o. for 60 days. Animals were sacrificed and blood samples collected for haematological and biochemical analysis. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: Results showed no significant changes in the weight of vital organs except in respect of the testes of the group treated with 2000 mg/kg extract which showed a significant (p<0.05) reduction in weight compared to the control group. There was a significant (p<0.01) increase in sperm motility and count of the group administered 80 mg/kg extract and a significant (p<0.001) reduction was observed at 2000 mg/kg. There were significant increases in the level of Hb and PCV at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, a significant decrease in AST and ALT levels at doses of 400 and 2000 mg/kg relative to control was observed. A significant reduction (p<0.05) in the level of total cholesterol (400 mg/kg) and increase (p<0.05) in level of HDL (80-2000 mg/kg) compared to control was observed. There was also significant (p<0.05) increase in the level of MDA and significant (p<0.05) decrease in SOD level in the testes at 2000 mg/kg. Histopathological assessment of the testes revealed abnormality at this dose. These effects were reversed after 30 days of cessation of administration of TO. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposure, with potential to elicit anti-anaemic effect, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low dose, the extract could be harmful to the testes on prolonged oral exposure at high dose.

A new Mg-Zn-Zr-Ca alloy in powder state was obtained via mechanical alloying method, from pure elemental powder. Further, the obtained powder-alloy was processed by selective laser melting (SLM) procedure to obtain 3D printed samples for small biodegradable implants. A series of microstructural, mechanical and corrosion analysis were performed. The SEM analysis of powder-alloy reveal a good dimensional homogeneity, with uniform colored, no agglutinated and almost rounded particles, suitable for selective laser melting procedure. Further, the SLM samples reveal a robust and unbreakable morphology, with a suitable porosity and without undesirable balling effect. The tested Young’s modulus of the SLM samples, of 42 GPa, is close to cortical bone one, of 30 GPa. The corrosion tests performed in PBS (Phosphate-buffered saline) solution show that the corrosion parameters have a satisfactory evolution.

Evidence regarding the role of oral antibiotics (oA) alone or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8,359 colorectal resections gathered over a 32-month period in 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1,013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA), and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSIs) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs 6 (2.5%) events; OR 3.77; 95%CI 1.22-11.67; p = .021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.

The oral cavity harbors hundreds of microbial species that are present either as planktonic cells, or incorporated into biofilms. The majority of the oral microbes are commensal organisms. Those that are pathogenic microbes can result in oral infections, and at times initiate systemic diseases. Biofilms that contain pathogens have been challenging to control. Many conventional antimicrobials have proven to be ineffective. Recent advances in science and technology are providing new approaches for pathogen control and containment and methods to characterize biofilms. This perspective provides: 1) A general understanding of biofilm development; 2) A description of emerging chemical and biological methods to control oral biofilms; 3) An overview of high-throughput analytical approaches to analyze biofilms.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.

Social biases may concentrate attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in significant part of responses to toxicity. It is unclear, however, if there are other molecular mechanisms which play important role in toxicity events but are overlooked by toxicology. To identify overlooked genes sensitive to chemical exposures we used publicly available databases. First, we used data on published chemical-gene interactions for 17,338 genes to estimate their sensitivity to chemical exposures. Next, we extracted data on publication numbers per gene for 19,243 human genes from Find My Understudied Genes database. Threshold were applied to both datasets using our algorithm to identify chemically sensitive and chemically insensitive genes and well-studied and underexplored genes. 1,110 underexplored genes highly sensitive to chemical exposures were used in GSEA and Shiny GO analyses to identify enriched biological categories. Metabolism of fatty acids, amino acids, and glucose were identified as underexplored molecular mechanisms sensitive to chemical exposures. These findings suggest that future effort is needed to uncover the role of xenobiotics in the current epidemics of metabolic diseases.

Nanoparticles (NPs) are commonly used in healthcare and nano therapy, but their toxicity at high concentrations is well-known. Recent research has shown that NPs can also cause toxicity at low concentrations, disrupting various cellular functions and leading to altered mechanobiological behavior. While researchers have used different methods to investigate the effects of NPs on cells, including gene expression and cell adhesion assays, the use of mechanobiological tools in this context has been underutilized. This review emphasizes the importance of further exploring the mechanobiological effects of NPs, which could reveal valuable insights into the mechanisms behind NP toxicity. Such investigations could aid in developing new strategies to mitigate NP toxicity and improve their safety for biomedical applications. Moreover, understanding how NPs affect cell cytoskeletal functions through mechanobiology could have significant implications, including the development of innovative drug delivery systems and tissue engineering techniques. In summary, this review highlights the significance of incorporating mechanobiology into the study of NP toxicity and demonstrates the potential of this interdisciplinary field to advance our knowledge and practical use of NPs.

Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in chemical, but not bacterial, constituents of these products. In this study, we explore the composition and function of the bacteriome in ST products from 4 countries using q-PCR and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4E+6) and highest in Yemeni shammah (6.6E+11). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus, Paenibacillus, and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas, Massilia, Propionibacterium, Puniceispirillum and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia, Desemzia, Atopostipes and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. PICRUSt functional prediction showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively “high carcinogenicity” products. The bacteriome of ST products thus differed qualitatively, quantitatively and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.

This paper presents a compartmental model aimed at investigating the pharmacokinetics of medical THC after oral administration. The model was developed to be multi-compartmental, describing the kinetics of THC and its metabolites in bodily tissues. Utilizing the law of mass action, the model was converted into ordinary differential equations (ODEs), illustrating the rate of concentration changes of THC and its metabolites in each compartment. Subsequently, we applied the nonstandard finite difference (NSFD) method to construct numerical solution schemes. These schemes were implemented in the MATLAB program, along with estimated pharmacokinetic rate constants. The results of the investigation demonstrate that the simulation curves depicting the plasma concentration-time profiles of THC and THC-OH closely resemble the actual data samples, indicating that this model accurately describes the pharmacokinetics of medical THC and its metabolites. Moreover, the model exhibits predictive capabilities regarding the pharmacokinetics of THC and its metabolites in various tissues. Consequently, the model serves as a valuable tool for enhancing our understanding of the pharmacokinetics of THC and its metabolites and for guiding adjustments to dosage and administration durations for oral medical THC products.

Caries are lesions caused by acidic compounds derived from the metabolism of bacteria such as streptococci. It is not merely the presence of acidogenic bacteria that causes caries but an imbalance in the oral biofilm microhabitat and its behavior. One factor underlying biofilm formation is quorum sensing (QS), that in gram-positives relies on peptidic molecules, whereas in gram-negatives is driven by small diffusible signals. Strategies based on QS inhibition have been proposed as alter-natives to antimicrobial therapies. Here, we investigate the antibiofilm potential of the lactonase enzyme Aii20J, previously reported as effective against biofilms of periodontal disease origin. We generated in vitro polymicrobial biofilms dominated by gram-positive taxa using supragingival samples from caries-free and caries-active children. The effect of Aii20J on the biofilms was evalu-ated regarding its biomass-reducing ability, as assessed with crystal violet assay, and its effects on the bacterial composition of the polymicrobial biofilms, as assessed by 16S community profiling. We describe significant biomass reductions upon Aii20J exposure without significant changes in bac-terial composition at the genus level. Our results support the use of Aii20J to prevent oral biofilm formation while highlighting the influence of the polymicrobial environment on bacterial commu-nities and their response to antibiofilm treatments.

Musabaqah Tilawatil Qurân (MTQ/Al Quran Reciting Competition) is often regarded as a big and important momentum for the process of Islamic preaching in Indonesia. It has even become a tradition for Indonesian people, although Al-Quran reciting is a common activity and a universal phenomenon in the Islamic world. In the MTQ event, the participants compete at various fields, including Tilawah (the art of reciting Al-Quran), Fahmil Qurân (comprehension of Al-Quran contents), and hifzul Qurân (memorization of Al-Quran verses). In 2003, a new field was initiated in the MTQ competition; i.e Musabaqah Makalah Ilmiah Al-Qurân (M2IQ/Al-Qurân Academic Writing Competition). Since its first exhibition on the 2003 Regional MTQ in West Java Province, and later on the 2008 National MTQ, the M2IQ, which is based on written-preach (dakwah bilkitabah), is considered as an innovation of preaching method in Indonesia. Islamic preaching (dakwah) in Indonesia has always been leaning heavily on the oral-preaching (dakwah bilisan) method, as represented by other fields contested in an MTQ. This development warrants a comprehensive study to understand what considerations underlying the emergence of M2IQ, how the process is, and what contributions it provides to the development of Islamic preaching in Indonesia. This study utilizes analytic-descriptive approach to discover the phenomenon. The findings indicate that M2IQ has accentuated the intellectual aspect of MTQ. In addition, M2IQ widens the spectrum of Al-Qurân preaching in Indonesia; opening a new chapter of Islamic preaching (dakwah) in the country.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p &lt; 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

Background: COVID-19 represents a threat for frailty patients. Objective: Investigate efficacy, safety and economic value of treatment with Molnupiravir in a cohort of fragile patients affected by COVID-19. Methods: Observational, prospective study. The data collected allowed to assess efficacy and safety of Molnupiravir in real life, compare the results with a subgroup of patients treated with Nirmatrelvir-Ritonavir and to effect a cost-effectiveness analysis. Results: In January-December 2022, 435 patients (225 males, 220 females; median age 72 years), were enrolled; 24 patients were unvaccinated, 280 patients had ≥2 risk factors. Molnupiravir appeared to give better results than the SOC both clinically and economically. In these patients in comparison with literature data or SOC, hospitalization was 2.5% vs 6.8% (p&lt;0.005), overall adverse effects 14,3% vs 30.4% (p&lt;0.0001), severe adverse effects 2.6 vs 6.9% (p&lt;0.001), thus involving a potential total savings of about € 92.954 per patient (8% of standard of care cost). Conclusions: early Molnupiravir treatment helped fragile patients who partially responded to vaccine, or with absolute contraindications to vaccination, to overcome COVID-19 without the need of hospitalization. Molnupiravir represents a clinical and economic effective treatment, avoiding disease progression in old patients suffering from multiple pathologies and taking several drugs.

Objective: A study was made of the salivary levels of adenosine deaminase (ADA), ferritin (FRR) and total proteins in healthy individuals and in patients with oral potentially malignant disorders (OPMD), assessing the potential role of saliva as a diagnostic tool. Methods: A total of 91 subjects participated in the study, divided into two groups: 59 patients with OPMD (oral leukoplakia or oral lichen planus )and 32 healthy controls with measurements being made of salivary ADA, ferritin (FRR) and total proteins (TP). Results: There were no significant differences in salivary ADA between the OPMD group and the controls (p=0.934), though the levels of both FRR and TP were significantly higher in the OPMD group (p=0.001). Patients with oral lichen planus showed significant differences in terms of FRR (p=0.009) and TP (p=0.003). Conclusions: The promising findings of this study suggest a potential role for FRR and TP in the salivary diagnosis of OPMD. In addition, saliva appears to be a reliable tool offering an interesting alternative for the screening of large populations.

COVID-19 vaccine hesitancy and its enablers would shape community uptake of non-covid vaccines such as oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included characteristics, intention to take OCV and COVID-19, reasons for COVID-19 hesitancy, and thinking and feeling about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude Prevalence Ratio, [cPR]=1.12, 95%CI[1.03-1.21]). Independent predictors of OCV hesitancy were living in semi-urban area (adjusted Prevalence Ratio [aPR]=1.10, 95%CI[1.03-1.12]), religious refusal of vaccines (aPR=1.06, 95%CI[1.02-1.12]), concerns about vaccine safety (aPR=1.05, 95%CI[1.01-1.11]) and adverse effects (aPR=1.06, 95%CI[1.01-1.12]), as well as poor knowledge (aPR=1.07, 95%CI[1.01-1.14]). Conversely, the belief about COVID-19 vaccine effectiveness reduced OCV hesitancy (aPR=0.76, 95%CI[0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibiting a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy interventions would likely improve the introduction of novel non-COVID-19 vaccines in post-COVID-19 era.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

This study describes a comparative in vitro study of the toxicity behavior of zinc oxide (ZnO) nanoparticles and micro-sized particles. The study aimed to understand the impact of particle size on ZnO toxicity by characterizing the particles in different media, including cell culture media, human plasma, and protein solutions (bovine serum albumin and fibrinogen). The study used various techniques such as atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to characterize the particles and their interactions with proteins. Hemolytic activity, coagulation time, and cell viability assays were used to assess ZnO toxicity. The results highlight the complex interactions between ZnO NPs and biological systems, including their aggregation behavior, hemolytic activity, protein corona formation, coagulation effects, and cytotoxicity. Moreover, the study indicates that ZnO nanoparticles are not more toxic than micro-sized particles, and the 50 nm particles resulted in general the least toxic. Furthermore, the study found that at low concentrations, no acute toxicity was observed. Overall, this study provides important insights into the toxicity behavior of ZnO particles and highlights that no direct relationship between nanometer size and toxicity can be directly attributed.

(1) Background: In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILE). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic drugs (AE), has become increasingly evident. (2) Methods: Data spanning a 10-year period (2010-2020) was analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. The study focused on reviewing relevant case reports detailing successful Intravenous lipid emulsion (ILE) administration in pa-tients with acute intoxications with antiepileptics, specifically examining the impact of fat emul-sions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval con-cerning hemodynamic instability. (3) Results: The typical symptoms of antiepileptic toxicity in-clude central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion ap-plication resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. (4) Conclusions: This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity.

Objective: The purpose of this study was to evaluate the surface texture and biofilm adhesion of veneered or CAD/CAM milled zirconia (partially stabilized with yttrium) after professional oral hygiene procedures. Samples (4x4 mm, thickness 2 mm; n = 72) were separated from zirconia blanks (3Y-TZP-LA). One group was veenired with ceramics and the other group of samples was CAD/CAM milled. Each group had 2 subgroups: polished and glazed. The samples were subjected to simulated strokes of professional brushing using abrasive paste and ultrasonic scaling. Parameters of surface micromorphology and receptivity to biofilm were calculated before and after simulating the given methods of professional maintenance of oral hygiene. The characteristics of zirconia surface were evaluated by scanning electron microscopy (SEM). Microbial bacterial/fungal species (Staphylococcus aureus, Streptococcus sanguinis and Candida albicans) were used and cultured on the respective sterilized zirconia surfaces. The amount of biofilm formation on zirconia surface was quantified by colony forming unit (CFU) counts. Results: SEM analysis showed the greatest change in surface microtopography after the use of ultrasonic scaling, in glazed zirconia samples. Less formation of colonies on the surface CAD/CAM milled zirconia restorations was observed. Conclusion: Routine methods of professional maintenance of oral hygiene can damage the surface of glazed zirconia restorations.

Background: The practice of self-medication is common worldwide and is an important component of medical self-care. However, the practice can be dangerous and is linked to various risks for the patients and the entire community. This study aimed to estimate the prevalence and factors associated with self-medication among Bangladeshi adults. Methods: A cross-sectional survey was conducted between April and June 2021 among Bangladeshi adults (aged &gt;19 years) using convenient sampling. A total of 1320 data were collected through face-to-face interviews using a standardized questionnaire. Multivariable logistic regression analysis was used to identify factors associated with self-medication practice (SMP). Results: Overall, 41% of adults in our survey reported SMP. The most common illnesses that prompted SMP were common cold/flu (66.4%), gastric problems (65%), and headache (64.4%). The most frequent reasons for SMP were to get better services (30.59%), perceive SMP without side effects (23.28%), and save time with effectiveness (14.56%). Potential risk factors included 10 years (AOR = 1.91; 95% CI: 1.04 - 3.50) and &gt;12 years of schooling (AOR = 5.03; 95% CI: 2.27 - 11.15), being a businessman (AOR = 4.64; 95% CI: 1.74 - 12.37), having ≤6 family members (AOR = 2.13; 95% CI: 1.40 - 3.24), being a member of a social group (AOR = 1.53; 95% CI: 1.10 - 2.12), a health status check after every six months (AOR = 1.52; 95% CI: 1.08 - 2.13), and current ill-health (AOR = 1.41; 95% CI: 1.06 - 1.87). Protective factors identified included ≤30 years of age (AOR = 0.40; 95% CI: 0.17 - 0.93), and practice of modern (AOR = 0.39; 95% CI: 0.22- 0.69) and herbal (AOR = 0.45; 95% CI: 0.21- 0.97) healing types. Conclusion: More than one-third of the study participants reported practicing self-medication. Increasing the community’s awareness of the extreme consequences of SMP and not just the average experience might sway individuals away from SMP, and implementing strict jurisdiction could be a way to minimize the SMP.

Abstract. Introduction: BMD study gives partial information on bone health in patients with TSH suppression therapy due to Differentiated Thyroid Cancer (DTC). TBS, a new parameter of bone microarchitecture is propose for bone quality study. This study analyze their long-term use in patients with DTC. Methods: BMD was measured by DXA and TBS with iNsigth software in 145 postmenopausal DTC patients. Vertebral Fractures (VFs) with a semi-quantitative x-ray method. Results: BMD at the end study was not different from initial. TBS decreased from 1.35±0.1 to 1.27±0.1 (p=0.002). PTH, Osteocalcin, and BAP were increased, suggesting increased bone remodeling. There was an increase in osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%); 31% had partially degraded and 15.1% degraded TBS changed to 48,9% and 24,8% at the end study. VFs in 30 patients, was not different in age, BMI, calcium and alcohol ingestion, smoking, radioiodine, or thyroid parameters vs. without VFs. Odds ratio for VFs increased with osteopenia (OR 2.63). Combination of TBS plus TBS did not improve discrimination. Conclusions: TBS was lowered while BMD did not differ. Percentage of osteoporosis and osteopenia and of partially degraded and degraded TBS was higher at the end study. Predominant discordance rate was found in partially degraded microarchitecture, in which the proportion of osteopenia was higher than normal or osteoporotic patients. AUC of TBS plus BMD did not improve discrimination. TBS, radioactive iodine, and sedentary lifestyle were the main differential data for patients with DTC and VFs.

Lake sediment records are of great importance for understanding the evolution of watershed environments. Various studies have been carried out to constrain the depositional ages of lake sediments and examine their physical, chemical, and biological characteristics, aiming to construct historical vegetation, environment and climate patterns in Chinese lake watersheds. In this study, we obtained relevant literature on lake sediment records by searching the key word 'age-depth' from the databases – Web of Science and China National Knowledge Infrastructure (CNKI, the largest Chinese academic database). We analyzed the literature based on its type (published in a Chinese/English journal or as a Master’s/PhD thesis), period of publication, journal (if published in a journal), key authors, study area, dating scale, and main aims. The results suggest that the lakes in the plateau regions are the most popular research topic typically covering 100–200 years (short-term) and 500–30,000 years (long-term). The literature focuses on a wide range of topics, from past environmental evolution in the watershed to lake ecology, and provides a solid foundation for better understanding regional climate change and the preservation of lake environments and ecosystems. In the future, resulting data from environmental reconstruction with lake sediments will be needed to integrate with emerging information processing technologies (e.g., artificial intelligence and meta-analysis), to disentangle the complex interplay between Earth surface processes and global climate change; furthermore, strengthening interdisciplinary collaboration will deepen our comprehension of man-land relationship and promote the sustainable management of lake ecosystems in the context of global climate change.

The health of inmates living in a restricted environment are affected by oral health behaviours and is related to their oral health-related quality of life (OHRQoL). We investigated oral health behaviours and oral symptoms among male inmates and analysed factors related to OHRQoL. Three hundred and seventy-six male inmates in two prisons were investigated using a self-reported questionnaire. The survey items included oral health behaviours, oral symptoms, self-esteem, and OHRQoL level. We analysed cross-correlations and factors related to OHRQoL. Toothbrushing after lunch and dinner was practiced by 83.5% of male inmates. ‘Food impaction’ was experienced by 45.4%. The OHRQoL level among male inmates was low, at 39.90 points. A hierarchical multiple regression model that controlled for general characteristics identified the following OHRQoL factors, in order of significance: trouble biting/chewing (β = -0.307), toothache (β = -0.154), temporomandibular joint disorder (β = -0.099), and periodontal health (β = 0.089). Self-esteem and OHRQoL were not significantly correlated. To ensure oral health in male inmates, the results of this study suggests that an oral health education programme, as well as provision of adequate dental care services, is required to increase appropriate oral health practice rates.

Use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated to exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally lower. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the tran-scriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP.

This article aims to provide a comprehensive understanding of vaping from various perspectives that contributes to the origin, development, achievement, and consequences of the greed of e-cigarette manufacturers. In our analysis, multiple elements of the social landscape, including economic, cultural, moral, psychological, and philosophical dimensions, contributed to the origin and development of the vaping greed and shaped people’s behaviors. Further discussion was made on how the specific characteristics of e-cigarette products and the marketing strategies of the companies, especially social media marketing, fostered the growth of such greed. Through interviews, we have also discussed the unfolding of this greed within the community of teenage vapers. The growth of the vaping greed was manifested in the large market share taken by the companies, but these all significantly harm people’s health and the communities. Nicotine and other chemicals in e-liquids promote each other’s negative effects in the mechanism leading to pulmonary symptoms and addiction, which are not limited to the physical level. We described that addiction could be transgenerational and can induce trauma both at an individual level and a community level. Overall, the greed of the vaping industry is a very complex system. The treatment of the greed shall be complicated as well: Besides the public health measures taken to treat the symptoms of the greed, we should educate individuals to be aware of their unfulfilled needs to regain authenticity and establish an infallible authority to enforce universal morality, which eradicates the complications of addiction and the root of the capitalists’ greed, respectively.

Increasing environmental distress is associated with a growing asthma incidence and, with no treatments available, montelukast (MTK) – an antagonist of the cysteinyl leukotrienes receptor 1 – is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions. Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as modulator of leukotriene pathways and systematize the knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Silicon nanoparticles (SiNPs) are highly promising for biological and biomedical applications, including bioimaging, due to their unique opltical properties (i.e. strong fluorescence and very high photostability). Their low or negligible in vitro toxicity has been reported, but in vivo toxicity and biological effects of SiNPs are still uncertain. Uncoated SiNPs were dispersed in distilled water via sonication, and their rapid aggregation was observed (319.0 ± 2.4 nm particle size). In vivo toxicity was studied using Danio rerio embryos and larvae. Rapid aggregation in their incubation medium was observed; besides that, SiNPs at 25 mg/L or higher concentration induced swim bladder malformation and/or death of the fish. The estimated LC50 value for 7-day larvae was 180 mg/L. This is the first in vivo toxicity study of uncoated and unfunctionalized SiNPs. To achieve better stability in biological media and lower toxicity, SiNPs should be covered with hydrophilic layers, but their absorption by cellular membranes may be weaker in this case.

(1) Background: As part of the Scottish Governments five-year recovery plan to address the backlog in NHS care following the COVID-19 pandemic, community pharmacies in Scotland are planned to provide a Hospital Discharge Medicines Supply and Medicines Reconciliation Service. We aimed to qualitatively explore patients’ experience of this new service; (2) Method: Adult patients (≥18yrs age) who consented to participate in the Community Pharmacy Hospital Dis-charge and Medicines Reconciliation Service were invited for interview within 21 days of dis-charge from hospital. Qualitative, one-to-one, semi-structured, patient interviews were conducted by telephone and audio-recorded using Microsoft Teams®. The interview audio recordings were transcribed verbatim and underwent thematic analysis; (3) Results: 12 patients were inter-viewed, evenly split by sex and with a median age of 62 years (range; 36 to 88 years). Analysis generated main five themes; Patient Engagement, Stakeholder Communication, Practical Factors, Human Factors, and Comparative Experiences. Many of these were interdependent; (4) Con-clusions: Patients appreciated that the service ensured a quicker discharge from hospital. Good stakeholder communication, practical factors (including choice, location, and the realities of ob-taining their medication from the community pharmacy), and a pre-existing and trusted rela-tionship in their usual community pharmacy were the key factors that regulated the patient ex-perience. In the main, patients were positive about the introduction of this new service. However, a lack of previous relationship or trust with a community pharmacy, and previous experiences with medication supply problems were factors which had the potential to negatively impact on patient experiences.

Safe water is a global public health concern amid increasing scarcity and pollution. Bottled water production and consumption contribute to these problems. This study examines tap water consumption in Italy, assessing associated sociodemographic factors and related health outcomes such as obesity and self-perceived health status. Data from the Italian National Statistics Institute's "Aspects of daily life" survey (N=45,597) were analyzed. Covariates included education, age, gender, economic status, region, concerns about waste and climate change, consumption of carbonated drinks excluding water, alcohol consumption, consumption of vegetables, consumption of snacks, body mass index, and self-perceived health status. Bivariate analyses and mixed-effect logistic regression models explored the associations. People who drink tap water were 19,674 with a higher prevalence in people aged 45 to 59 old, people with a graduate/post-graduate degree diploma, with optimal economic resources, and concerned about waste production and climate change, coming from the North-East regions of Italy. Underweight people showed a higher prevalence of TW assumption as well as those who drink less than occasionally carbonated drinks, drink alcohol, consume vegetables more than once a day, and snacks less than once a week with a satisfying level perceived health status. Regressions showed that all age classes are less likely to drink tap water than people younger than 20 years old. The category with “inadequate” economic resources is more likely to consume tap water. Low educational classes show a low likelihood of consuming tap water as well as Islands. A concern about waste production and climate change is associated with an increased likelihood of assuming tap water. Tap water consumption was negatively associate with obesity but not with a satisfactory Self-perceived health status. Insights from this study can inform public health strategies.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Productivity has been modest in construction due to many reasons, especially project-specific operations and fragmentation. The main aim of this research is to map the challenges towards industrialization in construction through a comparative study of the manufacturing industry. An inductive approach and a qualitative method are followed by applying semi-structured inter-views, and node-based thematic analysis. The key elements of industrialization in mature man-ufacturing companies are benchmarked. The findings indicate a specific order of steps for indus-trialization in construction. Data and information management with achieved systematization have been sources of productivity in manufacturing companies. However, the systematization starts from the offering, construction companies need to define their offering, that is the products, and define their respective data. Only accurate and good quality data on products enables the systematization of order delivery processes, which are the engine for a company’s success or failure. Continuous efficiency improvement is only possible with systematized processes and respective data related to the processes. The originality involves clarifying the industrialization of construction companies via products, respective data, and processes considering industrialized manufacturing companies.

Since the college years represent an important period for forming oral health behaviors during adulthood, it is important that college students establish proper oral health-promoting behaviors. Therefore, this study aims to identify the effects of oral health education experience, knowledge, and practice behaviors on oral health care self-efficacy among college students, as studies related to this topic are scarce. A total of 236 college students participated in a questionnaire survey comprising 21 questions. The collected data were analyzed through a chi-square test, independent-samples t-test, and logistic regression analysis using SPSS version 22.0. Participants with oral health education experience showed higher levels of oral health knowledge and practice behaviors than those who did not, and the odds of them having oral health care self-efficacy was 3.743 higher. Moreover, a one-unit increase in oral health knowledge and practice behaviors was associated with a 1.199 and 1.351 increase in oral health care self-efficacy, respectively. For oral health promotion among college students, oral health care self-efficacy reinforcement programs tailored to college students should be developed. These should focus on expanding oral health education opportunities to promote improvement in oral health care self-efficacy by strengthening oral health knowledge and the motivation to practice oral health behaviors.

Microplastics, which are plastic particles smaller than 5 mm in size, are a growing environmental concern since they have been found in oceans, rivers, lakes, and even on land. These tiny particles can escape water filtration systems and end up in water bodies as well as through the degradation of the larger plastic products causing serious environmental and food safety concerns. This research represents the magnitude of this pollution, characterization of microplastic contamination, its type of polymer, and possible sources of this pollution in the rivers around Dhaka, Bangladesh. Quantitative analyses were done following the method suggested by the NOAA and other conventional methods. Among the rivers, Buriganga has the highest microplastic pollution with 3.654 items/L in surface water and 43.125 items/kg in sediment. The concentration in Shitalakshya and Turag rivers are 3.011 items/L and 2.051 items/L in surface water and 34.875 and 17.875 items/kg in sediment respectively. ANOVA test revealed a significant difference between the concentration level of microplastic in the surface water of the Burigana and Turag rivers. A positive correlation between the concentration level of microplastic in the surface water and the sediment was also found. On average 58% of the microplastics were found to be fibrous in surface water. Qualitative analyses were done to find the characteristics and chemical composition of the microplastics. Through the use of FTIR spectroscopy, the study identified different kinds of synthetic polymers in the sample including polyamide (Nylon), polyethylene (PE), polystyrene (PS), polypropylene (PP), polyethersulfone (PES), polyvinyl chloride (PVC), and polyethylene terephthalate (PET) and polyethylene were the most abundant polymer in the samples. This study involved the investigation of three distinct rivers located in the vicinity of Dhaka city

The accompanying mechanical behavior during the flow of ore-rock dispersion is an important factor leading to the instability and failure of the orepass in the ore storage section. It is of great significance to accurately understand the instability characteristics of the well wall in the ore section, during the ore drawing process by understanding the flow characteristics and internal mechanical transfer mechanism of ore-rock dispersion. Using the discrete element method to analyze the flow characteristics, contact compactness, stress distribution characteristics and contact force probability distribution of the ore-rock dispersion, it realizes the quantitative characterization of the damage degree of ore-rock flow, and reveals the damage mechanism of mine storage wall. The results show that: (1) The friction between ore-rock particles, between ore-rock and well wall is an important reason for the change of the macroscopic flow form of ore-rock from “one” to “V” type. (2) The compactness and stress concentration of ores are increasing with the increase of storage depth, which is shown that with the increase of storage depth, the greater the probability of well wall instability. (3) The probability distribution of contact force strength between particles decreases exponentially in the whole process of ore drawing, in which the strong chain plays a major role in the stability of the dispersion system. (4) The number of overpressure and the overpressure coefficient can be used to quantitatively characterize the wall damage degree under the action of ore-rock flow. The dynamic side pressure decreases periodically in the form of exponential fluctuations, and the dynamic load formed by the ore-rock flow mainly played a role in the lower area of the ore storage section.

Patients with a psychotic disorder frequently report oral health problems, while mental health nurses (MHNs) seem not to be fully aware of these problems and the risk factors. Therefore, this study aims to develop supportive tools for MHNs regarding oral health to increase sensitization among MHNs and to provide MHNs with knowledge to recognize (potential) oral health problems in patients with a psychotic disorder. We used a human-centered design in which the user, MHNs as well as experts by experience, were placed in the centre of the research process. Problems and needs in MHNs working with patients with a psychotic disorder were addressed. To identify key issues of problem as well as the needs in terms of resources, we started with focus groups (n = 9). We analysed the data thematically based on context of patients and MHNs in practice regarding oral health, preferred oral health tools focused on MHN, and intended outcomes of tools. A Multi Criteria Decision Matrix was developed and analysed (n = 9) to identify the most optimal and viable solution based on established criteria and issues that are prevalent in the work of MHNs. Most promising result was the development of a brochure with an awareness screener. The brochure with awareness screener was developed as a low-fidelity prototype for MHNs regarding oral health in patients with a psychotic disorder, based on the latest scientific evidence. After testing it, the feasibility was tested through semi-structured interviews (n=19). MHNs and experts by experience were satisfied with the tool and provided recommendations for adjustments to the content. Significant augmentations to the brochure include a clinical lesson and a toothbrush with toothpaste for patients. We can conclude that a brochure with an awareness screener is feasible for MHNs. Future steps aiming to further refine and optimize care processes for oral health tools in MHNs, should take refining eligibility criteria for psychiatric populations and the language level of the target group of a tool into account.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Eelgrass meadows have attracted a lot of attention not only for their ability to maintain marine ecosystems as feeding grounds for marine organisms, but also for their potential to store atmos-pheric and dissolved CO2 as blue carbon. This study comprehensively evaluated the bacterial and chemical composition data obtained from eelgrass sediments of different scales along the coast of Japan to investigate the sediment effect on the acclimatization of eelgrass. Regardless eelgrass habitat, approximately 1% Anaerolineales, Babeliales, Cytophagales, and Phycisphaerales were present in the bottom sediment. Sulfate-reducing bacteria (SRB) were present at 3.69 % in eelgrass sediment compared to 1.70 % in bare sediment. Sulfur-oxidizing bacteria (SOB) were present at 2.81% and 1.10% in the eelgrass and bare sediment, respectively. Bacterial composition analysis and linear discriminant analysis revealed that sulfur-oxidizing bacteria detoxified H2S in the eelgrass meadows and that the larger-scale eelgrass meadows had a higher diversity of sul-fur-oxidizing bacteria. Our result indicated that one of the following systems detoxifies the H2S in eelgrass meadows microbial oxidation by sulfur-oxidizing bacteria, oxidation by O2 perme-ated by the physical diffusion of benthos. This study indicated the issues of maintaining sustain-able conservation of the eelgrass bed.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

The aims of this study were to assess oral health knowledge, attitudes, and practices among orthodontic patients between the ages of 15 and 17 years old compared to adolescents without orthodontic treatment. This cross-sectional study included 392 adolescents drawn from various French teaching hospitals. A closed-ended questionnaire was used to collect data. Adolescents undergoing orthodontic treatment had a higher knowledge of oral health than adolescents without orthodontic treatment. The majority of adolescents for both groups (69%) claimed to brush their teeth twice a day. Regarding complimentary dental material, 81.9% of adolescents without orthodontic treatment never used an interdental brush and 78.8% never used dental floss. For those undergoing orthodontic treatment, 48.5% never used interdental brush. Only 4% of adolescents without and 3% of adolescents with orthodontic treatment never consumed fizzy drinks, 4.9% and 3% never consumed sweets, 4% and 8.4% never ate fast-food. Adolescents without treatment consumed more sodas (p=0.04) and more fast food (p=0.03). Adolescents had insufficient knowledge of oral health. Health education programmes should be implemented to improve adolescents' knowledge and individual oral prophylaxis with interdental brushes.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of &lt;1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

The cork oak (Quercus suber L.), endemic essence of the Mediterranean Basin, is commonly used in traditional pharmacopoeia. The main objective of this work is to enhance the valorization of this plant species through the study of the anticandidosic activity of cork oak bark methalonic extracts in order to develop an efficient natural formulation for Candidiasis treatment.The anticandidosic activity of methanolic extracts of Q. suber bark stemming from decoction, maceration and Soxhlet methods of extraction in was tested on five different Candida albicans strains. Our results showed that all the tested extracts displayed an inhibitive activity, which varies according to the obtained extract and the tested strain. The best anticandidosic potential was observed with extracts obtained with Soxhlet method. The study of the acute toxicity showed that the lethal dose is 1150 mg/kg in mice, which remained moderately toxic according to Hodge and Sterner classification scale. Thus, this extract can be used in phytotherapy without danger in doses that are below 300 mg/kg of corporal weight. Based on these results, we can conclude that Cork oak bark extracts can be used to treat Candida albicans infections.

Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.