Background: The concept of flipped classrooms (FCs) is gaining attention in medical education as it aligns with the digital age’s demand for more interactive and accessible learning experiences. By shifting the delivery of instructional content outside of the classroom, an FC allows students to engage with materials at their own pace, thereby maximizing in-class time for discussions, problem-solving, and other active learning activities. Objective: This study aimed to conduct a comprehensive meta-analysis to appraise the comparative effectiveness of FC instruction in contrast to traditional pedagogical modalities, with a particular focus on postepidemic analyses within specific subfields of medical education. Methods: The PubMed, Web of Science, and Scopus databases were systematically searched for studies comparing academic outcomes between the FC and traditional learning approaches in medical education. The primary outcome measures were knowledge assessment and students’ satisfaction. The standardized mean difference (SMD) was used as a measure of the overall effect, and subgroup analysis was performed according to the study design (randomized controlled trial [RCT] vs observational). The Cochran Q test and Baujat plots were used to estimate heterogeneity, coupled with I2. Highly influential studies were identified; sensitivity analyses and metaregression were performed. Results: In total, 141 studies were included in the systematic review; 127 (90.1%) studies with 21,171 participants were included in the meta-analysis of students’ knowledge assessment, of which 37 (29.1%) were RCTs. FCs had significantly better outcomes than the traditional method in knowledge test scores in both observational studies and RCTs (SMD 0.90, 95% CI 0.59-1.20, P<.001 and SMD 0.93, 95% CI 0.65-1.22, P<.001, respectively). There was substantial heterogeneity among included studies (I2=95.2%, τ2=1.614; P<.001). The funnel plot showed high asymmetry with significant small study effects (P<.001). However, the effect estimate remained robust to the exclusion of highly influential studies in the sensitivity analysis. In total, 27 (21.3%) studies with a total of 5842 participants reported students’ satisfaction. Higher student satisfaction scores for FCs were demonstrated in contrast to control groups (SMD 0.82, 95% CI 0.45-1.19; P<.001). There was substantial heterogeneity among the included studies (I2=97.8%, τ2=0.913; P<.001) but no evidence for publication bias, and no studies were found to be influential. Conclusions: The FC method is associated with better knowledge achievement and greater student satisfaction than the traditional approach in medical education, paving the way for its broader integration into medical school curricula. However, it is essential to consider various factors, such as the availability of resources, faculty readiness, and student preferences when implementing any new educational approach. This study holds promise for advancing medical education by exploring innovative teaching methodologies that leverage technology to enhance learning outcomes.

Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.

Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-α, RANTES, TLR-2, HIF-1α, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-α were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-β, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.

Biodentine, a tricalcium silicate cement, has emerged as a retrograde root-end filling material to promote periapical lesion (PL) healing after apicoectomy. However, its underlying mechanisms remain unclear. This study tested the hypothesis that Biodentine stimulates the osteogenic differentiation of mesenchymal stromal cells (MSCs) derived from PLs. The Biodentine extract (B-Ex) was prepared by incubating polymerized Biodentine in RPMI medium (0.2 g/mL) for three days at 37 °C. B-Ex, containing both released microparticles and soluble components, was incubated with PL-MSCs cultured in either a basal MSC medium or suboptimal osteogenic medium. Osteogenic differentiation was assessed by Alizarin Red staining and the expression of 20 osteoblastogenesis-related genes. Non-cytotoxic concentrations of B-Ex stimulated the proliferation of PL-MSCs and induced their osteogenic differentiation in a dose-dependent manner, with a significantly enhanced effect in suboptimal osteogenic medium. B-Ex upregulated most early and late osteoblastic genes. However, the differentiation process was prolonged, as indicated by the delayed expression of wingless-type MMTV integration site family member 2 (WNT2), bone gamma-carboxyglutamate protein (BGLAP), bone morphogenic protein-2 (BMP-2), growth hormone receptor (GHR), and FOS-like 2, AP-1 transcription factor subunit (FOSL2), compared with their expression under optimal osteogenic conditions. The stimulatory effect of B-Ex was primarily calcium dependent, as it was reduced by 85% when B-Ex was treated with the calcium-chelating agent EGTA. In conclusion, Biodentine promotes the osteogenic differentiation of PL-MSCs in a calcium-dependent manner, supporting its stimulatory role in periapical healing.

Purpose: The main reason for writing this paper was the systematic determination of the state of internationalization of public higher education for the first time in Bosnia and Herzegovina (B&H). This paper aims to compare the state of internationalization with the results of comparative European and world research in higher education in order to determine the direction of public universities in B&H following globalization and connection with the European Higher Education Area (EHEA), as well as to determine future steps for mandatory inclusion into global higher education flows. Furthermore, the aim was to determine the treatment of mobility and student exchange programs and the ways of recognizing acquired qualifications abroad.Design/methodology/approach: The paper opted for a research study by conducting questionnaires that were divided into questions of elimination, questions of qualification and questions of the main survey. A total of 2,822 final year students were surveyed, as well as 386 representatives of the management of public universities. Within the paper, 25 different SWOT analyses of internationalization were performed by public universities, ministries and state/regional agencies, which was the basis for the SWOT analysis of the internationalization of B&H public higher education. The data were supplemented with a qualitative analysis of the obtained results compared with the International Association of Universities (IAU) and European Association for International Education (EAIE) research, as well as an overview of the most significant achievements in the field of internationalization of higher education.Findings: The paper provides empirical results on the barriers of students to study abroad, the existence of strategies and indicators for internationalization, the benefits of internationalization, internal and external drivers of internationalization and the potential risks of internationalization. These empirical results for B&H were compared with complementary IAUs and EAIE research and provided the basis for SWOT analysis of internationalization, development of institutional internationalization strategies and indicators, B&H recognition model, new criteria for accreditation with emphasis on internationalization and criteria for assessing internationalization. The paper suggests that virtual mobility and internationalization at home are future logical trends of development internationalization in B&H.Research limitations/implications: Suggestions for future research related to the examination of identified potential risks to the management of the internationalization of individual institutions, as well as to future comparisons of the new state of internationalization of higher education in B&H with current similar research in Europe and the world. Regarding the limitations in the research, it was possible that a larger number of participants participated in the survey with questionnaires, although the target set at the beginning of the survey was achieved.Practical implications: Most of the research results are the basis for improving the practical situation in the internationalization of public higher education in B&H. The paper presents a special chapter (undertaken improvement activities) dedicated to the practical implications based on the conducted research and comparison of results. Considering that this is a preliminary work related to the internationalization of higher education, based on the researched results, the context of the internationalization of public higher education in B&H was changed by the activities described in the mentioned chapter. The contribution to these activities was given by the approved project of the European Commission (EC) “strengthening of internationalization in B&H higher education” - STINT. Also, the research results of this paper offered a comparison with the research results of research conducted by IAUs and EAIE.Social implications: Different research groups participated in this research study: students, teachers, administration, representatives of ministries and state/regional agencies. All target groups supported the implementation of the questionnaire, the development of SWOT analyses and various reports, as well as the undertaking of various practical activities. In accordance with the research results, all these target groups were subsequently educated on issues of internationalization and recognition of qualifications. Stronger and better internationalization certainly increases the social impact on future students, higher education funders, as well as other interested stakeholders.Originality/value: This is a preliminary study whose main goal was to review the state of internationalization and to identify the most important undertaken activities in B&H. For the higher education area in B&H, the research study is new and has undertaken internationalization activities, but on the other side, in other developed European countries, similar studies and activities are not new. For the field of higher education in B&H, this work and research results are important because they will be the basis for future internationalization activities and will also serve as a basis for future activities to be undertaken in this field. The value of this paper is significant for both internal and external stakeholders of higher education.

Although a strong relationship between periodontal disease (PD) and atherosclerosis was shown in adults, little data are published in younger PD patients. Therefore, this study aimed to investigate and correlate clinical parameters of PD, pro- and immunoregulatory cytokines in gingival crevicular fluid (GCF) and serum, biochemical and hematological parameters associated with atherosclerosis risk, and carotid intima-media thickness (IMT) in our younger study participants (n = 78) (mean age 35.92 ± 3.36 years) who were divided into two equal groups: subjects with and without PD. PD patients had higher values of IMT, hs-CRP, triglycerides, total cholesterol, and LDL; most proinflammatory and Th1/Th17-associated cytokines in GCF; and IL-8, IL-12, IL-18, and IL-17A in serum compared to subjects without PD. These cytokines in GCF positively correlated with most clinical periodontal parameters. Clinical periodontal parameters, TNF-α and IL-8 in GCF and IL-17A, hs-CRP, and LDL in serum, had more significant predictive roles in developing subclinical atherosclerosis (IMT ≥ 0.75 mm) in comparison with other cytokines, fibrinogen, and other lipid status parameters. Hs-CRP correlated better with the proinflammatory cytokines than the parameters of lipid status. Except for serum IL-17A, there was no significant association of clinical and immunological PD parameters with lipid status. Overall, these results suggest that dyslipidemia and PD status seem to be independent risk factors for subclinical atherosclerosis in our younger PD population.