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Comparative evaluation of remineralization agents in severe enamel hypomineralization using a porcine enamel model

BMC Oral Health. 2026 Jun 29. doi: 10.1186/s12903-026-09043-6. Online ahead of print.

ABSTRACT

OBJECTIVES: To comparatively evaluate the effects of fluoride varnish, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) varnish, and self-assembling peptide P11-4 on the microhardness and surface morphology of hypomineralized enamel using a porcine model simulating molar incisor hypomineralization (MIH).

MATERIALS AND METHODS: Eighteen hypomineralized primary canines and needle teeth (the erupted third incisors of newborn piglets) obtained from three stillborn Yorkshire piglets were included in this in vitro study. Following stereomicroscopic examination, samples were randomly allocated into three groups (n = 6): Group 1: sodium fluoride (NaF) varnish, Group 2: NaF + CPP-ACP varnish, and Group 3: P11-4. Baseline microhardness (T0) was measured using a microhardness tester under a 300 g load for 15 s. Remineralization agents were applied according to manufacturers’ instructions. P11-4 application included prior sodium hypochlorite cleaning and phosphoric acid etching. Samples were stored in artificial saliva at 37 °C. Microhardness measurements were repeated at 1 week (T1) and 1 month (T2). One representative sample from each group was analyzed using scanning electron microscopy (SEM). Statistical analysis was performed using two-way repeated measures ANOVA and Bonferroni post hoc tests (p < 0.05).

RESULTS: Microhardness values significantly increased over time in all groups (p < 0.001). Significant differences were observed between all-time points (T0-T1, T0-T2, T1-T2) within each group. At T2, the P11-4 group demonstrated the highest microhardness values, followed by NaF + CPP-ACP and NaF groups (p < 0.05). Intergroup comparisons revealed statistically significant differences, particularly between P11-4 and the other groups at T2. SEM images demonstrated an irregular surface morphology related to mineral deposit accumulation after the application of remineralization agents. Nevertheless, in the P11-4 group, the covering deposits and crack-like lines appeared less scattered and more integrated than in the other treatment groups.

CONCLUSION: All remineralization agents improved enamel microhardness; however, P11-4 demonstrated superior efficacy compared to NaF + CPP-ACP and NaF varnish. Porcine enamel appears to be a reliable and biologically relevant model for simulating MIH-affected enamel in vitro.

PMID:42374455 | DOI:10.1186/s12903-026-09043-6

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Vitamin E administration reduces liver enzyme levels in patients with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD): evidence from a systematic review and meta-analysis

Nutr Metab (Lond). 2026 Jun 27. doi: 10.1186/s12986-026-01158-5. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent and frequently associated with elevated liver enzymes, indicating hepatic injury. Although vitamin E has been investigated as a therapeutic antioxidant, its effects on liver enzyme levels remain inconsistent. This study aims to systematically review and quantitatively synthesize the evidence of the effects of vitamin E administration on liver enzymes in patients with MASLD.

METHODS: A systematic search of scientific databases was conducted up to September 2025 to identify relevant randomized clinical trials (RCTs). Data on alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were extracted. Pooled effect sizes were calculated as weighted mean differences (WMD) with 95% confidence intervals (CIs) using a random-effects model.

RESULTS: The pooled analysis of 16 RCTs (22 effect sizes) showed that vitamin E administration significantly reduced serum liver enzyme levels in patients with MASLD, including AST (WMD: -5.94 IU/L), ALT (WMD: -7.33 IU/L), ALP (WMD: -5.68 IU/L), and GGT (WMD: -5.54 IU/L), all with statistical significance (p ≤ 0.008). Subgroup analyses revealed that longer intervention durations and higher vitamin E doses were generally associated with greater improvements in liver enzyme levels, particularly AST and ALT. In contrast, Significant reductions in ALP were mainly observed in shorter trials and with lower vitamin E doses, especially at higher doses and among obese populations. Overall, benefits were consistent across BMI categories, though effects appeared more pronounced in obese individuals.

CONCLUSION: Vitamin E supplementation was associated with significant reductions in serum liver enzymes, suggesting improvement in hepatocellular injury and necroinflammatory activity in patients with MASLD. However, the available evidence is insufficient to determine its effects on fibrosis progression, metabolic burden, or long-term liver-related outcomes.

PMID:42374454 | DOI:10.1186/s12986-026-01158-5

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Mavacamten alleviates sepsis-induced acute respiratory distress syndrome by modulating the PI3K/AKT/autophagy axis: a spatial transcriptomic-guided investigation

J Transl Med. 2026 Jun 27. doi: 10.1186/s12967-026-08431-4. Online ahead of print.

ABSTRACT

BACKGROUND: Sepsis-induced acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung condition with high mortality and no specific pharmacological treatments. The complex spatial heterogeneity of the lung during sepsis hinders the discovery of effective therapies. This study aimed to use spatial transcriptomics to map the septic lung’s molecular landscape to identify and validate a novel therapeutic agent.

METHODS: We performed spatial transcriptomics on lung tissues from mice subjected to cecal ligation and puncture (CLP) to model sepsis. A computational drug screen identified Mavacamten. In vitro, lipopolysaccharide-stimulated murine alveolar epithelial cells were used to assess Mavacamten’s effects on inflammation and cell injury. In vivo, CLP mice received Mavacamten, and we assessed survival, lung function, pulmonary edema, histology, and inflammatory markers. The underlying mechanism was investigated by analyzing the PI3K/AKT/mTOR pathway and autophagy markers. Statistical analyses included ANOVA, t-tests, and Kaplan-Meier analysis.

RESULTS: Spatial transcriptomics revealed distinct cellular clusters that were dramatically rearranged during sepsis. In vitro, Mavacamten significantly attenuated lipopolysaccharide-induced inflammation, cellular injury, and oxidative stress. In the CLP mouse model, Mavacamten treatment markedly improved 7-day survival, restored arterial oxygenation, reduced pulmonary edema, and lessened histological lung injury. Mavacamten also significantly lowered local and systemic pro-inflammatory cytokine levels. Mechanistically, Mavacamten reversed the sepsis-induced inhibition of autophagy and suppressed the activation of the PI3K/AKT/mTOR signaling pathway in lung tissues.

CONCLUSIONS: Mavacamten confers robust protection against sepsis-induced ARDS in a preclinical model by mitigating inflammation and lung injury, leading to improved survival. Its therapeutic action is mediated by inhibiting the PI3K/AKT pathway and restoring protective autophagy. Mavacamten is a promising candidate for repurposing in the treatment of sepsis-induced ARDS.

PMID:42374449 | DOI:10.1186/s12967-026-08431-4

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Physicians’ attitudes and perceived diagnostic confidence in point-of-care ultrasound in gynecology and obstetrics (GO-POCUS): a prospective single-center implementation study with structured training

BMC Med Educ. 2026 Jun 29. doi: 10.1186/s12909-026-09799-z. Online ahead of print.

ABSTRACT

BACKGROUND: Point-of-care Ultrasound (POCUS) is increasingly introduced in obstetrics and gynecology as a focused bedside extension of conventional ultrasound, although evidence on its implementation in routine care remains limited. This study examined physicians’ attitudes towards POCUS, their perceived diagnostic confidence across different clinical scenarios, and their preference for POCUS compared with standard ultrasound devices. These outcomes were assessed during early implementation in routine care accompanied by structured training.

METHODS: In this prospective, longitudinal implementation study, 22 physicians from a university department of gynecology and obstetrics evaluated standard ultrasound devices at baseline (T0a), completed a structured hands-on POCUS training, and assessed POCUS immediately after training (T0b) and after 2 weeks (T1), 1 month (T2), and 3 months (T3) of clinical use. Evaluations were conducted using repeated quantitative surveys. Outcomes were attitude (4 items, 7-point Likert), perceived diagnostic confidence in obstetric and gynecologic scenarios (17 items, 7-point Likert), and device preference (7-point Likert and dichotomous). Quantitative analyses included descriptive statistics, paired tests, mixed-effects models, and non-parametric sensitivity analyses.

RESULTS: Attitude toward POCUS was significantly more favorable than attitude toward standard devices at baseline (T0a 3.69 vs. T0b 5.83; p < .001) and remained high throughout follow-up. Perceived diagnostic confidence for POCUS was not higher immediately after training but increased significantly over time in both obstetrics and gynecology after independent clinical use (both p < .001). Highest confidence was observed in focused bedside scenarios relevant to rapid orientation and immediate decision-making, including fetal vitality assessment, placental localization, amniotic fluid assessment, postvoid residual urine measurement, and urinary tract obstruction, whereas confidence remained lower for more complex applications such as cervical length assessment, Doppler-based examinations, and fetal growth restriction. Preference for POCUS was already high at baseline and remained stable over time.

CONCLUSIONS: POCUS showed high acceptance in gynecologic and obstetric care from early implementation to routine use. Its clinical relevance appears greatest for focused mobile use and rapid bedside decision-making. These findings were observed during early implementation and support the role of POCUS as a complement to comprehensive ultrasound.

CLINICAL TRIAL REGISTRATION: German Registry of Clinical Trials; registration number: DRKS 00036941; date of registration: July 16, 2025; title: GO-POCUS: Point-Of-Care UltraSound in Gynecology and Obstetrics: Attitude and Perceived Diagnostic Confidence among Physicians.

PMID:42374445 | DOI:10.1186/s12909-026-09799-z

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Assessment of 21st century skills among health management students in Türkiye: a nationwide cross-sectional study

BMC Med Educ. 2026 Jun 27. doi: 10.1186/s12909-026-09727-1. Online ahead of print.

ABSTRACT

BACKGROUND: Twenty-first-century skills-such as critical thinking, problem solving, leadership, digital literacy, and innovation-are among the core competencies required for future health managers to function effectively within the complex and technology-driven structure of modern healthcare systems. The purpose of this study was to determine the 21st-century skill levels of undergraduate Health Management students in Türkiye and to examine whether these skills significantly differ according to demographic (gender, age, year of study) and academic (academic achievement and accreditation status) variables.

METHODS: This study employed a cross-sectional descriptive design. Data were collected via an online survey from 565 undergraduate Health Management students across Türkiye. The Multidimensional 21st Century Skills Scale, consisting of five subdimensions, was used as the data collection instrument. Descriptive statistics, independent samples t-test, one-way analysis of variance (ANOVA), and multiple regression analysis were performed to analyze the data. A significance level of p < .05 was adopted.

RESULTS: The overall 21st-century skill levels of the students were found to be above average. The highest mean scores were observed in the Career Consciousness and Information and Technology Literacy dimensions, whereas the lowest means were obtained in the Entrepreneurship and Innovation and Critical Thinking and Problem Solving subdimensions. Regarding gender, a significant difference was found only in the Career Consciousness dimension in favor of female students (p < .05). In general, increases in age and year of study were associated with higher 21st-century skill levels. Academic achievement produced significant differences particularly in Information and Technology Literacy and Critical Thinking skills. While no significant differences were found regarding the official accreditation status of universities, students’ perceived accreditation revealed significant differences in certain skill dimensions. Multiple regression analysis indicated that age and perceived accreditation were significant predictors of overall 21st-century skills.

CONCLUSIONS: Health Management students demonstrated strong profiles in career awareness and digital competencies, yet showed areas for development in critical thinking, innovation, and leadership. The findings suggest the importance of revising Health Management curricula in alignment with 21st-century skills, expanding experiential and project-based learning opportunities, and designing educational strategies that foster students’ innovation and entrepreneurship capacities.

PMID:42374438 | DOI:10.1186/s12909-026-09727-1

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Virtual reality-based training improves thoracentesis skills in medical interns: a randomized controlled trial

BMC Med Educ. 2026 Jun 27. doi: 10.1186/s12909-026-09801-8. Online ahead of print.

ABSTRACT

BACKGROUND: Thoracentesis is an essential clinical procedure, but its teaching is often limited by patient safety concerns and insufficient opportunities for repeated practice. Virtual reality (VR) offers immersive, repeatable simulation-based training; however, its effectiveness for thoracentesis has not been rigorously evaluated.

METHODS: In this randomized controlled trial, 20 medical interns were randomly assigned to either a VR-based training group (n = 10) or a traditional training control group (n = 10). The VR group received theoretical instruction plus VR simulation practice (1 h/day, 4 days/week for 3 weeks), while the control group received the same theoretical instruction plus traditional mannequin-based practice. All participants completed a 4-week training program. Outcomes were assessed at baseline, week 2, week 3, and week 4 using a standardized 300-point scoring rubric (preoperative, intraoperative, and postoperative components). Statistical comparisons were made using t-tests and chi-square tests. The primary outcome was the final thoracentesis procedural score at week 4.

RESULTS: No adverse events occurred. Baseline characteristics and initial assessment scores did not differ significantly between groups. At week 2, the VR group scored significantly lower than the control group (p < 0.05), reflecting an initial learning curve. However, at week 3 and week 4, the VR group significantly outperformed the control group (p < 0.01). At the final assessment, 80% (8/10) of the VR group achieved scores ≥ 270 points (excellent), compared to only 10% (1/10) of the control group.

CONCLUSION: VR-based training may improve thoracentesis procedural skills after an initial adaptation period. VR appears to be a useful adjunct to traditional medical education, though these findings are preliminary due to the small sample size.

PMID:42374433 | DOI:10.1186/s12909-026-09801-8

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The role of pictograms in improving patients’ medication adherence: a systematic review

BMC Health Serv Res. 2026 Jun 29. doi: 10.1186/s12913-026-14988-z. Online ahead of print.

ABSTRACT

BACKGROUND: Poor medication adherence remains a significant public health issue. Although pictograms are established as intuitive visual aids for medication guidance, a current evidence synthesis is lacking, particularly regarding their role in the rapidly advancing digital health landscape.

OBJECTIVE: To systematically evaluate the potential effect of pictograms on patients’ medication adherence and exploring implications for the digital health era.

METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data Knowledge Service Platform, VIP Network, and CBM databases for relevant studies on the effect of pictograms on patients’ medication adherence, from the inception of each database to April 27, 2025.

RESULTS: A total of 21 articles were included, comprising 19 English and 2 Chinese publications, all of which were randomized controlled trials. These studies varied in terms of study background, sample size, and drug regimens tested. All studies had methodological limitations, with pictographic interventions differing in complexity, duration, and adherence outcomes measured. Twelve studies (57.1%) reported statistically significant effects of pictographic interventions on patient adherence.

CONCLUSION: Pictograms serve as an effective adjunct to enhance medication adherence, particularly among patients managing complex medication regimens or possessing limited health literacy. Future efforts should focus on developing standardized, evidence-based pictogram libraries and integrating them into multimodal medication education systems. Incorporating pictograms into digital health platforms, such as those using AI and smart devices, represents a promising direction for enhancing their reach and impact.

PMID:42374421 | DOI:10.1186/s12913-026-14988-z

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Association of the atherogenic index of plasma and its integrative novel adiposity-based composites with all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome: novel adiposity-derived AIP indices provide modest incremental prognostic information

Cardiovasc Diabetol. 2026 Jun 29. doi: 10.1186/s12933-026-03277-y. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is recognized as a progressive pathophysiological continuum linking metabolic dysfunction, dysfunctional adiposity, chronic kidney disease, and cardiovascular injury. The atherogenic index of plasma (AIP) reflects lipid-related atherogenic burden, whereas novel adiposity indices, including body roundness index (BRI), weight-adjusted waist index (WWI), and a body shape index (ABSI), capture body-shape-related adiposity burden. However, the associations of AIP and AIP-based adiposity composite indices with mortality outcomes across the CKM spectrum remain unclear. This study aimed to evaluate the associations of AIP and integrative AIP-based composite indices, including AIP-BRI, AIP-WWI, and AIP-ABSI, with all-cause and cardiovascular mortality among individuals across CKM stages.

METHODS: We conducted a retrospective cohort analysis using prospectively collected data from 22,587 US adults in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Following the 2023 American Heart Association (AHA) Presidential Advisory, participants were classified into a hierarchical staging framework (Stages 0-4) to reflect the CKM disease continuum. Primary outcomes were all-cause and cardiovascular mortality, identified through linkage to the National Death Index. Integrative AIP-based composite indices were constructed by directly multiplying AIP by each adiposity index, including BRI, WWI, and ABSI, yielding AIP-BRI, AIP-WWI, and AIP-ABSI, respectively. These indices were evaluated as integrated exposure variables reflecting the combined burden of atherogenic dyslipidemia and adiposity-related body shape. All analyses incorporated complex survey weights to ensure national representativeness. Survey-weighted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Model 2 adjusted for demographic and socioeconomic characteristics, lifestyle factors, blood pressure, and total cholesterol. Nonlinear associations were examined using restricted cubic splines (RCS). Incremental prognostic value was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

RESULTS: During follow-up, non-survivors exhibited significantly higher baseline integrative composites than survivors (P < 0.001). In the fully adjusted model (Model 2), which adjusted for demographic and socioeconomic characteristics, lifestyle factors, blood pressure, and total cholesterol, each standard deviation increase in the integrative composites was independently associated with a higher risk of all-cause mortality: AIP-BRI (HR, 1.09; 95% CI, 1.05-1.14), AIP-WWI (HR, 1.07; 95% CI, 1.02-1.11), and AIP-ABSI (HR, 1.07; 95% CI, 1.02-1.11). These point estimates were numerically slightly higher than that of stand-alone AIP (HR, 1.06; 95% CI, 1.01-1.10), but the differences should be interpreted cautiously. For cardiovascular mortality, the corresponding HRs were 1.17 (95% CI, 1.09-1.27) for AIP-BRI, 1.11 (95% CI, 1.03-1.21) for AIP-WWI, and 1.11 (95% CI, 1.02-1.20) for AIP-ABSI, compared with 1.10 (95% CI, 1.02-1.20) for AIP. RCS analyses revealed J-shaped associations, with a clinical risk threshold for AIP-BRI at 1.57. Subgroup analyses indicated that these associations were most evident in participants aged < 50 years. Adding BRI to AIP assessment yielded a statistically significant but modest NRI of 3.10% for cardiovascular mortality.

CONCLUSION: Across the CKM spectrum, higher AIP-based adiposity composite indices, particularly AIP-BRI, were associated with increased risks of all-cause and cardiovascular mortality, especially among younger individuals. However, their incremental predictive improvement was modest, suggesting that these indices may serve as supplementary exploratory markers rather than stand-alone tools for CKM risk stratification.

PMID:42374419 | DOI:10.1186/s12933-026-03277-y

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Breaking stereotypes or making compromises? gender, income, and the unequal landscape of medical specialty choice

BMC Med Educ. 2026 Jun 29. doi: 10.1186/s12909-026-09797-1. Online ahead of print.

ABSTRACT

BACKGROUND: Medical specialty choice shapes both physician identity and healthcare systems. Specialty choices are influenced not only by academic interest and aptitude but also by gender norms and socioeconomic pressures. While these dynamics are well documented in high income settings, fewer studies examine how perceived gender roles and income expectations jointly influence specialty preferences in LMICs contexts.

METHODS: This sequential mixed methods study combined a cross-sectional online survey with semi structured interviews. The quantitative phase included 155 medical students (response rate 79.5%) and examined associations between demographic characteristics and specialty preferences. The qualitative phase comprised 34 interviews purposively sampled across all five cohorts. Interview data were analyzed thematically using Braun and Clarke’s six step framework, following an inductive and reflexive approach guided by Social Cognitive Career Theory to explore how students understood and negotiated gender norms, income potential, and workload intensity.

RESULTS: Quantitative analysis showed no statistically significant associations between income-based specialty preference and gender, GPA, family income, hometown, or high school background (all p > 0.05). High income specialties were selected by 60 students (39%), low-income specialties by 26 (17%), and other fields by 69 (44%), with similar gender distribution across these groups (p = 0.81). In contrast, qualitative analysis revealed pronounced gendered patterns. Many female students chose specialties they perceived as low intensity, often citing anticipated caregiving responsibilities and work life balance concerns as reasons for avoiding surgery, emergency medicine, and other high intensity fields. Male students frequently reported social and familial pressure to pursue prestigious or high-income specialties, prioritizing financial stability and provider roles even when these conflicted with personal interests. Across both genders, themes highlighted the centrality of perceived income, prestige, mentorship inequities, and cultural narratives of sacrifice in shaping career compromises.

CONCLUSION: Specialty choice among medical students in LMICs reflects not only personal interest but also structural inequities linked to gender norms and income expectations. Although quantitative analysis of demographic factors did not independently predict specialty preferences, qualitative findings revealed powerful social pressures that shape career compromises. Targeted, gender sensitive career counselling, equitable mentorship, and financial support are needed to enable students to choose specialties that align with their values and competencies.

PMID:42374415 | DOI:10.1186/s12909-026-09797-1

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Clinical subphenotypes in septic patients with new-onset atrial fibrillation: validation and parsimonious classifier model development

BMC Med Inform Decis Mak. 2026 Jun 27. doi: 10.1186/s12911-026-03652-5. Online ahead of print.

ABSTRACT

BACKGROUND: The substantial heterogeneity among septic patients with new‑onset atrial fibrillation (NOAF) complicates intensive care unit (ICU) management, and the absence of a parsimonious subphenotype classifier has impeded the implementation of personalized therapeutic strategies. In this study, we aim to identify the subphenotype of septic patients with NOAF, develop a concise classifier model, and reveal the differential efficacy of heart-rate control therapies across these subphenotypes.

METHODS: This retrospective study utilized data from the Medical Information Mart in Intensive Care (MIMIC)-IV and MIMIC-III database. Consensus clustering based on hierarchical clustering was employed for subphenotype derivation. Nine supervised classifiers were employed to construct the subphenotype classifier, including random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), partial least squares (PLS), neural network (NN), naïve Bayes (NB), linear discriminant analysis (LDA), least absolute shrinkage and selection operator (LASSO), and adaptive boosting (AdaBoost.M1). Subphenotype-specific propensity score-derived stabilized inverse probability of treatment weights was used to weight comparisons of intensive care unit and hospital lengths of stay and discharge dispositions across subphenotypes.

RESULTS: Among 1535 septic patients with NOAF, three distinct subphenotypes emerged: Phenotype A was the mildest subgroup; Phenotype B exhibited pronounced metabolic acidosis, highest anion gap, severe renal impairment, and elevated severity scores; Phenotype C showed intermediate laboratory values and score profiles with notable hyperchloremia and inflammatory markers. A parsimonious model established by SVM showed the best effectiveness. HR-control therapy was associated with subphenotype-specific reductions in hospital and ICU lengths of stay and more favorable discharge dispositions in Phenotype A, while more favorable survival outcomes were observed across all three subphenotypes in IPTW-weighted analyses.

CONCLUSION: Cluster analysis revealed three clinically relevant subphenotypes among septic patients with NOAF, each demonstrating distinct clinical outcomes and heterogeneous responses to heart rate control therapy.

PMID:42374411 | DOI:10.1186/s12911-026-03652-5