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This study aims to investigate the pre-service teachers' experiences with online teaching, but also to uncover the challenges and opportunities for improving the distance education in the future. A qualitative research approach using phenomenology is adapted for the study. The participants were 18 pre-service teachers studying at the different programs of the University of Prishtina's Faculty of Education. The interviews were conducted online. The transcripts of interviews were analyzed using the interpretative phenomenological analysis. Five themes were derived from the analysis of the interview data: quality of teaching activities, positive aspects of online teaching, limitations, factors affecting online teaching, and recommendations to improve online teaching and learning in the future. This study proved the importance of pre-service teachers' interest and motivation, but also the faculty lecturers' professional preparedness for online teaching. Findings revealed the inability to relate theory to practice during online teaching as a lack of interaction between the university and the schools. This study is expected to serve as a guide for the expectations of preservice teachers towards the improvement of distance education in the future.

Government One-Stop Shops are promoted as a strategy for improving intergovernmental collaboration, coordinating “Weberian” bureaucratic structure, and streamlining service delivery using technology. One-stop-shop models, which are seen as a significant accomplishment in recent e-government initiatives, aim to provide public service delivery mechanisms that are efficient, accessible, coordinated, and cost-effective. The purpose of this research paper is to assess citizens’ satisfaction with the quality of integrated public services provided by One-Stop Shop (OSS), with a particular emphasis on the relationship between citizen satisfaction with the quality of OSS services and determinant dimensions of trust, procedures, staff skills and qualifications, time and cost savings, and perceived citizen care/support. This paper employs a quantitative approach method through a survey as a research instrument. A structured questionnaire is distributed to 114 citizens receiving service in OSS in a municipality in south Albania, a western Balkan country. The study’s primary objective is to provide top-level managers of the OSS agencies and policymakers with an effective instrument for better evaluating and understanding the perceived quality of their integrated public services offered from the perspective of their citizens. This understanding aims to facilitate the formulation of more effective policies and strategies that foster the ongoing enhancement and incorporation of novel public management best practices. The findings of the multi-regression analysis reveal that the factors - Saving, Staff, Support, Procedures, and Trust had a positive and statistically significant impact on satisfaction, accounting for 85.8 per cent of the variation values of citizen satisfaction with the quality service provided by One-Stop Shop.

Objective: To assess changes in physical activity (PA) after a COVID-19 shutdown on a primarily residential university campus. Methods: Eighty students, faculty, and staff (FS) of a university (age: 32.2 ± 13.6 yr) who wore a consumer wearable technology (CWT) device completed an anonymous survey by inputting data for 30 days prior to- and 30 days following an academic break in 2020, in which the university transitioned to remote learning. Results: Steps decreased after spring break in all subjects (p < 0.001), but steps were impacted to a greater extent in students. 30-day, weekday, and weekend step averages all decreased in students (p < 0.001). FS were able to maintain their weekend step averages. Conclusions: PA decreased in a university community after the COVID-19 shutdown. Students, no longer active transport for campus life, saw a greater impact on their PA. These changes could have an impact on health status.

Objective: To determine differences in glucose control and cardiovascular disease risk factors following three weeks of added soda, 100% fruit juice, or water in apparently healthy, college-aged adults. Participants: Thirty-six adults (18 males; 18 females) between the ages of 18 and 30 years of age. Methods: A 3-arm randomized controlled parallel-arm trial; at baseline and after three weeks consuming the assigned beverage, participants completed glucose control and cardiovascular disease risk factor assessments. Results: There were no significant differences between beverage conditions for glucose control or cardiovascular disease risk factors (ps > 0.05). There were no significant changes in caloric intake or differences in caloric intake between conditions, p = 0.17. p Conclusions: In healthy, young adults, under free-living conditions, short-term consumption of two commercially packaged servings of SBs did not lead to significant glucose control or cardiovascular disease risk factor changes, indicating potential compensation and/or resilience to negative short-term effects.

This study investigated student teachers' teaching self-efficacy level and factors that predict it (using five-factor mentoring model). Two hundred and ten third and fourth-year student teachers (N=100/N=110; 93.8% females) were involved in the study and asked to complete a self-report questionnaire. The "Mentoring for Effective Primary Teaching" instrument and "Teachers' Sense of Efficacy Scale" were used to collect the data. Findings indicated that higher levels of student teachers' self-efficacy are positively associated with the level of mentoring experience during the teaching practicum. The results found that fourth-year students reported significantly higher levels of teaching self-efficacy than third-year students. This study reported that there is a significant mean difference in student teachers' self-efficacy beliefs in terms of having parents in the teaching profession. A multiple regression found that mentor teachers' personal attributes are the best predictor of student teachers' teaching self-efficacy beliefs.

Alzheimer's disease (AD) is the most common cause of late-life dementia characterized by progressive neurodegeneration and brain deposition of amyloid-β (Aβ) and phosphorylated tau. The APOE ε2 encoding apolipoprotein E (APOE2) is a protective allele against AD among the three genotypes (APOE ε2, ε3, ε4), while APOE4 is the strongest genetic factor substantially increasing AD risk. APOE regulates brain lipid homeostasis and maintaining synaptic plasticity and neuronal function, where APOE2 has a superior function compared to APOE3 and APOE4. Gene therapy that increases APOE2 levels in the brain is, therefore, a promising therapeutic strategy for AD treatment. We previously reported that PEGylated liposomes conjugated with transferrin and a cell-penetrating peptide Penetratin sufficiently deliver chitosan-APOE2 cDNA plasmid complex into the brain of wild-type mice. Here, we investigated how brain-targeting liposome-based APOE2 gene delivery influences Aβ-related pathologies in amyloid model AppNL-G-F knockin mice at 12-month-old. We found a trend of reductions of insoluble Aβ levels in the mouse cortices 1 month after APOE2 gene therapy. Furthermore, in the AppNL−G-F knockin mice that received the APOE2 gene therapy, brain transcriptome analysis through RNA-sequencing identified the upregulation of genes/pathways related to neuronal development. This was supported by increases of Dlg4 and Syp mRNAs coding synaptic proteins in the experimental group. On the other hand, we found that APOE2 gene delivery increased soluble Aβ levels, including oligomers, as well as exacerbated neurite dystrophy and decreased synaptophysin. Together, our results suggest that brain-targeting liposome-based APOE2 gene therapy is potentially beneficial for synaptic formation at the transcriptional level. Forced APOE2 expressions, however, may exacerbate Aβ toxicity by increasing the dissociation of Aβ oligomers from aggregates in the presence of considerable amyloid burden.

This paper looks at the incorporation of blockchain and Internet of Things (IoT) technologies into Forest 4.0, a sector that harnesses advanced tools such as artificial intelligence and big data for efficient and sustainable forest monitoring and management. The synergy of blockchain and IoT has gained significant attention, offering a secure and decentralized framework for data management, traceability, and supply chain oversight. The provided use cases demonstrate how these technologies improve forest practices, with insight into smart contract implementation and decentralized systems for sustainable forest management. The major findings imply that digital technologies such as blockchain, IoT, AI, WSNs, etc. can help improve forest management sustainability, efficiency and transparency, and integration of these technologies can provide significant information for decision-making and resource allocation, as well as improve supply chain transparency and sustainable forest practices.

Background. Pregnancy is an important period in a woman's life characterized by numerous physiological changes that can affect their oral health. For effective results, concerns about oral health during pregnancy should be checked and managed. Aim of the study was to assess the knowledge, attitudes, and reported practices regarding oral health among pregnant women in Pristina. Method. A descriptive cross-sectional study design was used, conducted in Pristina with a sample of 251 pregnant women treated at the University Clinical Center of Gynecology, in the Antenatal Care Department. The questionnaire included socio-demographic characteristics, obstetric history, women's knowledge of oral health, attitude toward oral health on the Likert Scale, and oral health practices. Results. The study revealed that 70.11% of the interviewed women were aged ≥25 years, and 46.2% of them were from rural areas. Unemployed women comprised 66.1% of the studied group, and 45.41% of pregnant women were educated. The study results indicate that 54% of the surveyed women know about oral health. Less than half, 27.9%, agreed on the importance of dental check-ups during the first trimester, and about 35.9% lacked knowledge that poor oral hygiene could cause premature birth. The majority, 54%, of surveyed women brush their teeth more than once a day. Discussion. The lack of professional knowledge is high, and most pregnant women need more information regarding this issue. Additionally, dental examinations are not performed on mothers, making it impossible to determine their current dental treatment needs. Conclusion. Pregnant women's knowledge appears deficient in almost all variables included in the study, despite the majority choosing the correct alternative, a significant percentage of them responded with “don't know”.

Patient satisfaction is a key indicator of the quality of health care delivery, and as an internationally recognized factor must be studied on a regular basis to ensure the health care systems' performance. The study's scope is to identify and evaluate the factors influencing patient satisfaction with the quality of public primary health care. A three-month cross-sectional facility-based study with 150 participants was carried out. A structured questionnaire based on the SERVPERF method is used to collect respondents' opinions about the quality of healthcare provided by primary healthcare services. Tangibles, Reliability, Assurance, and Waiting Time in Healthcare Centers were found to be statistically significant and affect overall satisfaction with healthcare service quality. The study's findings will help Primary health center managers and policymakers develop strategies and evaluate future applications to support improving quality of care, healthcare outcomes and overall primary health center performance.

This article presents a systematic literature review on hybrid recommendation systems (HRS) in the e-commerce sector, a field characterized by constant innovation and rapid growth. As the complexity and volume of digital data increases, recommendation systems have become essential in guiding customers to services or products that align with their interests. However, the effectiveness of single-architecture recommendation algorithms is often limited by issues such as data sparsity, challenges in understanding user needs, and the cold start problem. Hybridization, which combines multiple algorithms in different methods, has emerged as a dominant solution to these limitations. This approach is utilized in various domains, including e-commerce, where it significantly improves user experience and sales. To capture the recent trends and advancements in HRS within e-commerce over the past six years, we review the state-of-the-art overview of HRS within e-commerce. This review meticulously evaluates existing research, addressing primary inquiries and presenting findings that contribute to evidence-based decision-making, understanding research gaps, and maintaining transparency. The review begins by establishing fundamental concepts, followed by detailed methodologies, findings from addressing the research questions, and exploration of critical aspects of HRS. In summarizing and incorporating existing research, this paper offers valuable insights for researchers and outlines potential avenues for future research, ultimately providing a comprehensive overview of the current state and prospects of HRS in e-commerce.

The aim of the present in vitro comparative study is to validate a novel composite polymer, named “ONLY”, developed to overcome the mechanical drawbacks of conventional, metal-reinforced poly(methyl methacrylate) (PMMA) interim restoration. Ten interim restorations were designed and fabricated (five in the composite “ONLY” group, and five in the metal-reinforced PMMA group). All the samples were screwed into the prototype models, simulating a complete edentulous mandible rehabilitated with six straight implants. Outcome measures were break point (load, N) and displacement (mm) through a static compression test, and material behavior through a dynamic cyclic test method (fatigue test). A total of 20 samples were tested (10 for static and 10 for dynamic). In each group, five samples (test and control) were used. All the specimens completed the mechanical tests, as planned. There was no statistically significant difference between groups for any test. In the test group, the break point was 1953.19 ± 543.73 N, while it was 2031.10 ± 716.68 N in the control group (p = 0.775). The displacement was 1.89 ± 0.34 mm in the test group and 1.98 ± 0.75 mm in the control group (p = 0.763). Using the dynamic cyclic test method, in the control group the mean load was 2504.60 ± 972.15 N, while in the test group the mean load was 3382.00 ± 578.50 N. The difference between groups was 877.40 ± 579.30 N (p value = 0.121). Within the limitations of this in vitro study, the novel composite polymer can be used to immediately load dental implants. Further clinical research is needed to confirm these preliminary results.

There is little information about outcomes that persist beyond graduation for college students who take interdisciplinary innovation courses. This project describes qualitative results of a study of college graduates who were members of two such courses in different disciplines at two universities in the United States. Teamwork, innovation, and learning are themes the participants identified as skills from the courses that they use in their post-graduation work. Study results can be used to create/assess such courses and as a foundation for studying student outcomes for future interdisciplinary innovation courses.

This paper invites a conversation between world-systems perspective and radical criminology to contribute to a more robust materialist, historical, and global understanding of policing, prisons, and carceral power. We trace the genealogy of these two approaches to the larger transformations of global capitalism in the 1960s and 1970s, including ruling class responses to capitalist crises vis a vis neoliberal restructuring as well as the social struggles waged by antisystemic movements. Both world-systems and radical criminology brought a critical and Marxist perspective to the liberal social sciences, yet dialogue between them has been lacking. On the one hand, world-systems analysis offers a structural explanation of capitalism but often side steps the role that carceral power plays to manage the system’s deepening contradictions. On the other hand, radical criminology focuses on carceral power but often limits its analysis to advanced core countries and not to the entire capitalist system. We argue that bringing these two critical approaches together can offer us a renewed Marxist perspective to the interrelated issues of capitalist crisis and carceral power and thus make possible new lines of inquiry and research best suited for grappling with the major contradictions of capitalism in the twenty-first century.

Rapid development of digital technologies has stemmed profound changes in the society, positioning the ICT sector as a key driver and contributor. This sector, including education, is however characterized by a gender gap, which is problematic in the light of the increasing demand for digital competence and the ability to move toward a sustainable egalitarian society. In this study, we argue for a need to explore the concept of ICT in higher education. This involves assessing the success of educational programs in attracting women and exploring the perceptions of female students regarding their academic environment. With a specific focus on Sweden, through a survey involving 82 respondents, we provide evidence on motivations and perceptions of women regarding leading choices on pursuing ICT higher education. We propose a holistic approach to studying gender representation and inclusion in ICT higher education, with a focus on women’s perceptions, experiences, and suggestions.

It is unknown whether oxygen uptake (V̇O2) sampling intervals influence the efficacy of a verification stage following a graded exercise test (GXT). Fifteen females and 14 males (18–25 years) completed a maximal treadmill GXT. After a 5 ​min recovery, the verification stage began at the speed and grade corresponding with the penultimate stage from the GXT. Maximal oxygen consumption (V̇O2max) from the incremental GXT (iV̇O2max) and V̇O2max from the verification stage (verV̇O2max) were determined using 10 seconds (s), 30 ​s, and 60 ​s from breath ​× ​breath averages. There was no main effect for V̇O2max measure (iV̇O2maxvs. verV̇O2max) 10 ​s ([47.9 ​± ​8.31] ml∙kg−1∙min−1 vs [48.85 ​± ​7.97] ml∙kg−1∙min−1), 30 ​s ([46.94 ​± ​8.62] ml∙kg−1∙min−1 vs [47.28 ​± ​7.97] ml∙kg−1∙min−1), and 60 ​s ([46.17 ​± ​8.62] ml∙kg−1∙min−1 vs [46.00 ​± ​8.00] ml∙kg−1∙min−1]. There was a stage ​× ​sampling interval interaction as the difference between (verV̇O2max−iV̇O2max) was greater for 10-s than 60-s sampling intervals. The verV̇O2max was > 4% higher than iV̇O2maxin 31%, 31%, and 17% of the tests for the 10-s, 30-s, and 60-s sampling intervals respectively. Sensitivity for the plateau was < 30% for 10-s, 30-s, and 60-s sampling intervals. Specificity ranged from 44% to 60% for all sampling intervals. Sensitivity for heart rate ​+ ​respiratory exchange ratio was > 90% for all sampling intervals; while specificity was < 25%. Findings from the present study suggest that the efficacy of verification stages for eliciting a higher V̇O2max may be influenced by the sampling interval utilized.

Abstract Objectives The aim of this study was the assessment of the efficiency of the ethyl acetate (EthOAc) extract of Thymus serpyllum against Candida albicans and to compare it with sodium hypochlorite (NaOCl) and chlorhexidine (CHX), as well as their genotoxic effect. Material and Methods The antifungal effectiveness of the EthOAc extract of Thymus serpyllum was determined using the agar disk diffusion method. The inhibition zones induced by the EthOAc extract were compared after 5 min, 60 min, and 24 h to those induced by standard solutions (2% CHX and 2% NaOCl). An in vitro genotoxicity assay was performed in cultured lymphocytes from the blood of human volunteers to observe micronuclei formation. Statistical analysis of the results was performed using the Kruskal–Wallis test and one‐way analysis of variance. Results The inhibition zone of combination of CHX with EthOAc extract of Thymus serpyllum against C. albicans was 29.7 mm after 5 min, 28.3 mm after 60 min, and 29 mm after 24 h. The inhibition zone of NaOCl in combination with EthOAc extract of Thymus serpyllum against C. albicans was 0 mm. The EthOAc extract of Thymus serpyllum did not show a genotoxic effect on lymphocyte cells. Conclusions The EthOAc extract of Thymus serpyllum in combination with CHX may be a useful root canal disinfection in endodontic therapy.

Southern leaf blight (SLB) is a foliar disease caused by the fungus Cochliobolus heterostrophus infecting maize plants in humid, warm weather conditions. SLB causes production losses to corn producers in different regions of the world such as Latin America, Europe, India, and Africa. In this paper, we demonstrate a non-destructive method to quantify the signs of fungal infection in SLB-infected corn plants using a deep UV (DUV) fluorescence spectrometer, with a 248.6 nm excitation wavelength, to acquire the emission spectra of healthy and SLB-infected corn leaves. Fluorescence emission spectra of healthy and diseased leaves were used to train an Autoencoder (AE) anomaly detection algorithm-an unsupervised machine learning model-to quantify the phenotype associated with SLB-infected leaves. For all samples, the signature of corn leaves consisted of two prominent peaks around 450 nm and 325 nm. However, SLB-infected leaves showed a higher response at 325 nm compared to healthy leaves, which was correlated to the presence of C. heterostrophus based on disease severity ratings from Visual Scores (VS). Specifically, we observed a linear inverse relationship between the AE error and the VS (R2 = 0.94 and RMSE = 0.935). With improved hardware, this method may enable improved quantification of SLB infection versus visual scoring based on e.g., fungal spore concentration per unit area and spatial localization.

Automation of plant phenotyping using data from high-dimensional imaging sensors is on the forefront of agricultural research for its potential to improve seasonal yield by monitoring crop health and accelerating breeding programs. A common challenge when capturing images in the field relates to the spectral reflection of sunlight (glare) from crop leaves that, at certain solar incidences and sensor viewing angles, presents unwanted signals. The research presented here involves the convergence of 2 parallel projects to develop a facile algorithm that can use polarization data to decouple light reflected from the surface of the leaves and light scattered from the leaf’s tissue. The first project is a mast-mounted hyperspectral imaging polarimeter (HIP) that can image a maize field across multiple diurnal cycles throughout a growing season. The second project is a multistatic fiber-based Mueller matrix bidirectional reflectance distribution function (mmBRDF) instrument which measures the polarized light-scattering behavior of individual maize leaves. The mmBRDF data was fitted to an existing model, which outputs parameters that were used to run simulations. The simulated data were then used to train a shallow neural network which works by comparing unpolarized 2-band vegetation index (VI) with linearly polarized data from the low-reflectivity bands of the VI. Using GNDVI and red-edge reflection ratio we saw an improvement of an order of magnitude or more in the mean error (ϵ) and a reduction spanning 1.5 to 2.7 in their standard deviation (ϵσ) after applying the correction network on the HIP sensor data.

Background: Monitoring SARS-CoV-2 seroprevalence dynamics during the COVID-19 pandemic is crucial for understanding population immunity and providing insights into public health policies. Limited data exist on this from Albania and other Eastern European countries. This study aimed to investigate SARS-CoV-2 seroprevalence in Albania, comparing August 2021 and August 2022 data from two representative samples of the general population. The objective was to understand the temporal dynamics of SARS-CoV-2 antibodies across age groups and assess the impacts of natural infection and vaccination on population immunity. Methods: This longitudinal study was conducted in two consecutive cross-sectional assessments 12 months apart in Albania's urban all-ages population. IgG anti-Spike-1 and anti-Nucleoprotein SARS-CoV-2 antibodies were measured using ELISA, focusing on seropositivity rates and antibody levels. Methods: The study encompassed 2143 and 2183 individuals in August 2021 and 2022, respectively, with the anti-S1-IgG seropositivity rate escalating from 70.9 ​% to 92.1 ​%. In 2021, seroprevalence ranged from 49.6 ​% (0–15 years) to 82 ​% (>60 years). By August 2022, it surpassed 90 ​% in most age groups, except 0–15 years (73.8 ​%). ''Hybrid'' immunity (COVID-19+ and Vaccine+) reached 56.6 ​% in 2022, or 2.8 times higher than in 2021, exhibiting the highest antibody levels compared to the only vaccinated or previously COVID-19-infected individuals. Conclusion: This study highlights an overall 94 % seroprevalence in the Albanian population in August 2022 and robust ''hybrid'' immunity, suggesting substantial protective immunity against SARS-CoV-2. The lower immunity in the 0–15 age group underscores the necessity for youth-targeted vaccine campaigns. These findings provide valuable insights for shaping healthcare measures and vaccination policies.

This study aims to understand pre-service teachers' perceptions about mentor teachers' mentoring practices and their relevance to the level of their teaching self-efficacy. A survey was conducted with a sample of 210 pre-service teachers in the 3rd and 4th year of a 4-year bachelor program for elementary teacher education at the University of Prishtina. Semi-structured interviews were conducted with 10 pre-service teachers who reported their highest levels of mentoring experience were with mentor teachers' personal attributes, whilst the lowest level of experience was with feedback provision. Furthermore, they reported their lowest levels of self-efficacy beliefs were in the classroom management domain. Results showed that a lack of close mentoring relationships combined with a lack of institutional (faculty) support and commitment to student professional development had a negative impact on pre-service teachers' perceptions of their experiences. Findings indicate that the quality of mentoring may be enhanced when mentors display attributes such as hospitality, openness to collaboration, non-prejudicial approaches, space for engagement, and encouragement to take initiatives. More information about system requirements, more feedback, more support, and closer rapport with mentors can contribute to higher teaching self-efficacy for pre-service teachers.

Background: This study aims to assess the changes in COVID-19 seroprevalence among the adult urban population of Albania between July and December 2020, when the Wuhan strain of SARS-CoV-2 virus was still prevalent in the country. Methods: Two independent, randomly selected samples of individuals aged 20–70 years residing in Metropolitan Tirana, Albania, were collected in June–July and December 2020. ELISA method was used for serological testing to determine IgG antibodies anti-S1-SARS-CoV-2. Results: The proportion of individuals classified as seropositive in early July was 7.5% (95% CI: 4.3%–10.7%), which increased 6.5 times in late December 2020, reaching 48.2% (95% CI: 44.8%–51.7%). The increasing seroprevalence rates in the study mirrored the trend of detected COVID-19 cases from June to December 2020 in Albania. However, they demonstrate a much higher cumulative incidence of the SARS-COV-2 infection in the community than the reported COVID-19 cases. Conclusion: The rapid increase in SARS-CoV-2 seroprevalence observed in Tirana City by the end of 2020 was likely a result of several factors, including the very low infection exposure between March–May 2020 when the entire city was in a lockdown, followed by the high susceptibility of the population due to naïve immunity. Despite the high observed seroprevalence at the end of December 2020, COVID-19 incidence continued to increase in Albania through 2021 and 2022 following the new virus variant surges.

Plants have the capacity to respond to conserved molecular features known as microbe-associated molecular patterns (MAMPs). The goal of this work was to assess variation in the MAMP response in sorghum, to map loci associated with this variation, and to investigate possible connections with variation in quantitative disease resistance. Using an assay that measures the production of reactive oxygen species, we assessed variation in the MAMP response in a sorghum association mapping population known as the sorghum conversion population (SCP). We identified consistent variation for the response to chitin and flg22-an epitope of flagellin. We identified two SNP loci associated with variation in the flg22 response and one with the chitin response. We also assessed resistance to Target Leaf Spot (TLS) disease caused by the necrotrophic fungus Bipolaris cookei in the SCP. We identified one strong association on chromosome 5 near a previously characterized disease resistance gene. A moderately significant correlation was observed between stronger flg22 response and lower TLS resistance. Possible reasons for this are discussed.

Ariana Kameri,1 Arben Haziri,2 Zeqir Hashani,3 Agime Dragidella,1 Kemajl Kurteshi,4 Arsim Kurti5 1Department of Dental Pathology and Endodontics, University of Prishtina “Hasan Prishtina”, Faculty of Medicine, Prishtina, Kosova; 2Department of Chemistry, Natural Science Faculty, University of Prishtina “Hasan Prishtina”, Prishtina, Kosova; 3Education Faculty, University of Prizren “Ukshin Hoti”, Prizren, Kosova; 4Department of Biology, Natural Science Faculty, University of Prishtina “Hasan Prishtina”, Prishtina, Kosova; 5Department of Microbiology, Medical Faculty, University of Prishtina “Hasan Prishtina”, Prishtina, KosovaCorrespondence: Agime Dragidella, Department of Dental Pathology and Endodontics, University of Prishtina “Hasan Prishtina”, Faculty of Medicine, Rrethi i spitalit, p.n, Prishtina, 10000, Kosova, Tel +383 44 130 674, Fax +383 38 512 525, Email agime.dragidella@uni-pr.eduPurpose: With the demand for better efficiency during endodontic therapy, the purpose of this in vitro study was to evaluate the efficiency of ethyl acetate (EthOAc) extract of Matricaria chamomilla (L.) against Enterococcus faecalis and compare with standard root canal irrigation solutions.Material and Methods: The antibacterial effect against Enterococcus faecalis of the EthOAc extract of Matricaria chamomilla was assessed without, or with dentine powder, using agar disk diffusion method. The inhibition zones induced by the EthOAc extract were observed after 5 minutes, 60 minutes, and 24 hours and compared with standard irrigation solutions (2% chlorhexidine and 2% sodium hypochlorite) without, or after mixing with dentine powder. Statistical analysis of the results were analysed with the Kruskal–Wallis test and one-way ANOVA.Results: There was no inhibition zone in samples with and without dentine powder after combination of ethyl acetate extract of Matricaria chamomilla with sodium hypochlorite. When the extract was used alone in samples without dentine powder, the inhibition zone was 9.7 mm after 24 h, but this zone was decreased after adding dentine powder (7.7 mm). When the extract was used in combination with CHX, the inhibition zone in samples with dentine powder was 25.3 mm, but it was decreased after adding dentine powder (21.7 mm).Conclusion: The EthOAc extract of Matricaria chamomilla as alternative root canal irrigant may be a useful natural agent with antibacterial activity against Enterococcus faecalis. Also, it showed promising results in endodontic therapy after combination with chlorhexidine in Enterococcus faecalis eradication.Keywords: root canal, herbal plants, diffusion method, chlorhexidine, sodium hypochlorite

Abstract Background The rare p.H157Y variant of TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) was found to increase Alzheimer’s disease (AD) risk. This mutation is located at the cleavage site of TREM2 extracellular domain. Ectopic expression of TREM2-H157Y in HEK293 cells resulted in increased TREM2 shedding. However, the physiological outcomes of the TREM2 H157Y mutation remain unknown in the absence and presence of AD related pathologies. Methods We generated a novel Trem2 H157Y knock-in mouse model through CRISPR/Cas9 technology and investigated the effects of Trem2 H157Y on TREM2 proteolytic processing, synaptic function, and AD-related amyloid pathologies by conducting biochemical assays, targeted mass spectrometry analysis of TREM2, hippocampal electrophysiology, immunofluorescent staining, in vivo micro-dialysis, and cortical bulk RNA sequencing. Results Consistent with previous in vitro findings, Trem2 H157Y increases TREM2 shedding with elevated soluble TREM2 levels in the brain and serum. Moreover, Trem2 H157Y enhances synaptic plasticity without affecting microglial density and morphology, or TREM2 signaling. In the presence of amyloid pathology, Trem2 H157Y accelerates amyloid-β (Aβ) clearance and reduces amyloid burden, dystrophic neurites, and gliosis in two independent founder lines. Targeted mass spectrometry analysis of TREM2 revealed higher ratios of soluble to full-length TREM2-H157Y compared to wild-type TREM2, indicating that the H157Y mutation promotes TREM2 shedding in the presence of Aβ. TREM2 signaling was further found reduced in Trem2 H157Y homozygous mice. Transcriptomic profiling revealed that Trem2 H157Y downregulates neuroinflammation-related genes and an immune module correlated with the amyloid pathology. Conclusion Taken together, our findings suggest beneficial effects of the Trem2 H157Y mutation in synaptic function and in mitigating amyloid pathology. Considering the genetic association of TREM2 p.H157Y with AD risk, we speculate TREM2 H157Y in humans might increase AD risk through an amyloid-independent pathway, such as its effects on tauopathy and neurodegeneration which merit further investigation.