Epigenetic markers of tooth eruption - DNA methylation and histone acetylation.

The present study aimed to evaluate whether epigenetic markers are expressed in the dental follicles surrounding ectopically erupting teeth. Twenty-one dental follicles were collected in 20 adolescent children through surgical exposure of ectopic teeth. The epigenetic modifications of DNA methylation and histone acetylation were evaluated by immunohistochemistry. The results showed cells positive for DNA-methyltransferase 1 (DNMT1), DNA methyltransferase 3 beta (DNMT3B), ten-eleven translocation-2 (TET2), acetyl-histone H3 (AcH3), acetyl-histone H4 (AcH4), 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC) were present in all the samples. The levels of epigenetic markers representing active chromatin (5hmC, AcH3, AcH4, and TET2) were statistically significantly higher than those of markers representing inactive chromatin (5mC, DNMT3B, DNMT1). In conclusion, follicles in ectopic teeth display major epigenetic modifications. In the follicles, epigenetic markers associated with the activation of bone-related genes are more abundant than markers associated with the inactivation of bone-related genes.

Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review.

Dental implant surfaces and their unique properties can interact with the surrounding oral tissues through epigenetic cues. The present scoping review provides current perspectives on surface modifications of dental implants, their impact on the osseointegration process, and the interaction between implant surface properties and epigenetics, also in peri-implant diseases. Findings of this review demonstrate the impact of innovative surface treatments on the epigenetic mechanisms of cells, showing promising results in the early stages of osseointegration. Dental implant surfaces with properties of hydrophilicity, nanotexturization, multifunctional coatings, and incorporated drug-release systems have demonstrated favorable outcomes for early bone adhesion, increased antibacterial features, and improved osseointegration. The interaction between modified surface morphologies, different chemical surface energies, and/or release of molecules within the oral tissues has been shown to influence epigenetic mechanisms of the surrounding tissues caused by a physical-chemical interaction. Epigenetic changes around dental implants in the state of health and disease are different. In conclusion, emerging approaches in surface modifications for dental implants functionalized with epigenetics have great potential with a significant impact on modulating bone healing during osseointegration.

Decontamination of biofilm-contaminated implant surfaces: An in vitro evaluation.

OBJECTIVES: The aim of the present study was to evaluate the cleaning efficacy of two mechanical and two chemical protocols in the decontamination of implant surfaces. METHODS: In total, 123 commercially available implants were mounted in plastic models mimicking peri-implant circumferential intra-bony defects. A multispecies biofilm was grown on implant surfaces. Mechanical (air-polishing (AP), rotating titanium brush (TiB)) and chemical decontamination (alkaline electrolyzed water, N-acetyl-L-cysteine) protocols were used. Cleaning efficacy in terms of residual biofilm area, chemical surface properties, and bacterial counts were analyzed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and quantitative polymerase chain reaction. RESULTS: Surface decontamination protocols including use of an AP device or a rotating TiB were superior in terms of biofilm removal and in reducing atomic% of Carbon on implant surfaces when compared to methods restricted to wiping with gauze. The use of chemical agents as adjuncts to the mechanical cleaning protocols provided no relevant overall benefit over saline. No treatment modality, however, resulted in complete biofilm removal. CONCLUSION: Air-polishing and rotating TiB were more effective implant surface decontamination protocols than wiping with gauzes. Use of chemical agents did not improve cleaning efficacy.

Polymorphism in epigenetic regulating genes in relation to periodontitis, number of teeth, and levels of high-sensitivity C-reactive protein and glycated hemoglobin: The Tromsø Study 2015-2016.

BACKGROUND: The aim of this study was to investigate the association between periodontitis and four single nucleotide polymorphisms (SNPs) in genes involved in epigenetic regulation of DNA, and between these same SNPs and tooth loss, high-sensitivity C-reactive protein (hs-CRP), and glycated hemoglobin (HbA1c) levels. METHODS: We included participants with periodontal examination (n = 3633, aged: 40-93 years) from the Tromsø Study seventh survey (2015-2016), Norway. Periodontitis was defined according to the 2017 AAP/EFP classification system as no periodontitis, grades A, B, or C. Salivary DNA was extracted and genotyping was performed to investigate four SNPs (rs2288349, rs35474715, rs34023346, and rs10010325) in the sequence of the genes DNMT1, IDH2, TET1, and TET2. Association between SNPs and periodontitis was analyzed by logistic regression adjusted for age, sex, and smoking. Subgroup analyses on participants aged 40-49 years were performed. RESULTS: In participants aged 40-49 years, homozygous carriage of minor A-allele of rs2288349 (DNMT1) was associated with decreased susceptibility to periodontitis (grade A: odds ratio [OR] 0.55; p = 0.014: grade B/C OR 0.48; p = 0.004). The minor A-allele of rs10010325 (TET2) was associated with increased susceptibility to periodontitis (grade A OR 1.69; p = 0.035: grade B/C OR 1.90; p = 0.014). In the entire sample, homozygous carriage of the G-allele of rs35474715 (IDH2) was associated with having ≤24 teeth (OR 1.31; p = 0.018). Homozygous carriage of the A-allele of TET2 was associated with hs-CRP≥3 mg/L (OR 1.37; p = 0.025) and HbA1c≥6.5% (OR 1.62; p = 0.028). CONCLUSIONS: In this Norwegian population, there were associations between polymorphism in genes related to DNA methylation and periodontitis, tooth loss, low-grade inflammation, and hyperglycemia.

Surface decontamination of explanted peri-implantitis-affected implants.

AIM: The present study aimed at evaluating the effect of air-polishing (AP) and a combination of AP and alkaline electrolysed water (AEW) in surface decontamination of explanted peri-implantitis-affected implants. MATERIALS AND METHODS: Twenty-five patients with 34 dental implants scheduled for explantation due to severe peri-implantitis were included. Following implant removal, the apical part of each implant was embedded in acrylic blocks. Implants were randomly allocated to surface decontamination using AP with or without AEW. Four implants were left untreated and used as negative controls. Specimens were analysed using scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). Area of residual bacteria was the primary outcome. RESULTS: SEM analysis revealed that both treatment protocols were effective in biofilm removal and only small proportions of target areas of the implants showed residual bacterial or mineralized deposits. Although differences between the treatment protocols were small, implant thread loci (top/flank/valley), zones of the implant (apical/middle/coronal), implant surface characteristics and gender influenced the results. In addition, EDS analysis showed that zones influenced the atomic% of carbon and calcium and that implant surface characteristics affected the atomic% of titanium. CONCLUSIONS: AP, with or without AEW, is an effective method in removing biofilm from peri-implantitis-affected implants.

Nurses' experiences of person-centred care planning using video-conferencing.

AIM: The aim was to illuminate how nurses experience person-centred care planning using video conferencing upon hospital discharge of frail older persons. DESIGN: Care planning via video conferencing requires collaboration, communication and information transfer between involved parties, both with regard to preparing and conducting meetings. Participation of involved parties is required to achieve a collaborative effort, but the responsibilities and roles of the involved professions are unclear, despite the existence of regulations. METHOD: A qualitative content analysis was conducted based on 11 individual semi-structured interviews with nurses from hospitals, municipalities and primary care in Sweden. RESULTS: This study provides valuable insights into challenges associated with care planning via video conferencing. The meeting format, that is video conferencing, is perceived as a barrier that makes the interaction challenging. Shortcomings in video technology make a person-centred approach difficult. The person-centred approach is also difficult for nurses to maintain when the older person or relatives are not involved in the planning.

BMP Gene-Immobilization to Dental Implants Enhances Bone Regeneration.

For individuals who have experienced tooth loss, dental implants are an important treatment option for oral reconstruction. For these patients, alveolar bone augmentation and acceleration of osseointegration optimize implant stability. Traditional oral surgery often requires invasive procedures, which can result in prolonged treatment time and associated morbidity. It has been previously shown that chemical vapor deposition (CVD) polymerization of functionalized [2.2]paracyclophanes can be used to anchor gene encoding vectors onto biomaterial surfaces and local delivery of a bone morphogenetic protein (BMP)-encoding vector can increase alveolar bone volume and density in vivo. This study is the first to combine the use of CVD technology and BMP gene delivery on titanium for the promotion of bone regeneration and bone to implant contact in vivo. BMP-7 tethered to titanium surface enhances osteoblast cell differentiation and alkaline phosphatase activity in vitro and increases alveolar bone regeneration and % bone to implant contact similar to using high doses of exogenously applied BMP-7 in vivo. The use of this innovative gene delivery strategy on implant surfaces offers an alternative treatment option for targeted alveolar bone reconstruction.

Influence of epigenetics on periodontitis and peri-implantitis pathogenesis.

Periodontitis is a disease characterized by tooth-associated microbial biofilms that drive chronic inflammation and destruction of periodontal-supporting tissues. In some individuals, disease progression can lead to tooth loss. A similar condition can occur around dental implants in the form of peri-implantitis. The immune response to bacterial challenges is not only influenced by genetic factors, but also by environmental factors. Epigenetics involves the study of gene function independent of changes to the DNA sequence and its associated proteins, and represents a critical link between genetic and environmental factors. Epigenetic modifications have been shown to contribute to the progression of several diseases, including chronic inflammatory diseases like periodontitis and peri-implantitis. This review aims to present the latest findings on epigenetic influences on periodontitis and to discuss potential mechanisms that may influence peri-implantitis, given the paucity of information currently available.

Cellular expression of epigenetic markers and oxidative stress in periodontitis lesions of smokers and non-smokers.

OBJECTIVE: To evaluate differences in the cellular expression of epigenetic markers and oxidative stress in periodontitis lesions between current smokers and non-smokers. BACKGROUND: Tobacco smoking is recognized as one of the major risk factors for periodontitis. However, the mechanisms by which smoking affects the progression of the disease remain to be determined. METHODS: Twenty-five current smokers and 21 non-smokers with generalized severe periodontitis were included. From each patient, one soft tissue biopsy from a periodontitis site was harvested and prepared for histological analysis. The infiltrated connective tissue (ICT) was selected as the region of interest to assess the cellular expression of epigenetic markers and reactive oxygen/nitrogen species (RONS) by immunohistochemistry. RESULTS: Although the ICT of smokers and non-smokers did not differ in size or in the expression of markers for DNA damage or oxidative stress, current smokers presented with significantly lower area proportions and densities of cells positive for the epigenetic markers DNMT1 and AcH3. In addition, periodontitis lesions in current smokers presented with a diminished antimicrobial activity, as indicated by significantly lower densities and area proportions of NOX2- and iNOS-positive cells. CONCLUSIONS: Components of the host response and epigenetic mechanisms in periodontitis lesions in smokers are downregulated as opposed to lesions of non-smokers.

Global DNA Methylation in Dental Implant Failure Due to Peri-Implantitis: An Exploratory Clinical Pilot Study.

BACKGROUND: Peri-implantitis (PIT) is highly prevalent in patients with dental implants and is a challenging condition to treat due to the limited outcomes reported for non-surgical and surgical therapies. Therefore, epigenetic therapeutics might be of key importance to treat PIT. However, developing epigenetic therapeutics is based on understanding the relationship between epigenetics and disease. To date, there is still scarce knowledge about the relationship between epigenetic modifications and PIT, which warrants further investigations. AIM: The purpose of this study was to evaluate the level of global DNA methylation associated with implant failure (IF) due to PIT compared to periodontally healthy (PH) patients. MATERIAL AND METHODS: A total of 20 participants were initially enrolled in this pilot, exploratory, single-blinded, cross-sectional clinical human study in two groups: 10 in the PH group and 10 in the IF group. In the participants who have completed the study, gingival tissue and bone samples were harvested from each participant and were used to perform global DNA methylation analysis. The percentage of global DNA methylation (5-mC%) was compared (1) between groups (PH and IF); (2) between the subgroups of gingival tissue and bone separately; (3) in the whole sample, comparing gingival tissue and bone; (4) within groups, comparing gingival tissue and bone. Demographic, periodontal, and peri-implant measurements as well as periodontal staging, were also recorded. All statistical comparisons were made at the 0.05 significance level. RESULTS: Out of the initially enrolled 20 patients, only 19 completed the study and, thus, were included in the final analysis; 10 patients in the PH group and 9 patients in the IF group, contributing to a total of 38 samples. One patient from the IF group was excluded from the study due to systemic disease. The mean implant survival time was 10.8 years (2.17-15.25 years). Intergroup comparison, stratified by group, indicated a similar 5-mC% between the PH and IF groups in both gingival tissue and bone (p = 0.599), only in bone (p = 0.414), and only in gingival tissue (p = 0.744). Intragroup comparison, stratified by the type of sample, indicated a significantly higher 5-mC% in gingival tissue samples compared to bone in both the PH and IF groups (p = 0.001), in the PH group (p = 0.019), and in the IF group (p = 0.009). CONCLUSIONS: Within the limitations of this study, higher global DNA methylation levels were found in gingival tissue samples compared to bone, regardless of the study groups. However, similar global DNA methylation levels were observed overall between the IF and PH groups. Yet, differences in the global DNA methylation levels between gingival tissues and bone, regardless of the study group, could reflect a different epigenetic response between various tissues within the same microenvironment. Further studies are necessary to elucidate the present findings and to evaluate the role of epigenetic modifications in IF due to PIT.

Understanding the role of endotoxin tolerance in chronic inflammatory conditions and periodontal disease.

OBJECTIVE: This review aims to present the current understanding of endotoxin tolerance (ET) in chronic inflammatory diseases and explores the potential connection with periodontitis. SUMMARY: Subsequent exposure to lipopolysaccharides (LPS) triggers ET, a phenomenon regulated by different mechanisms and pathways, including toll-like receptors (TLRs), nuclear factor kappa-light-chain enhancer of activated B-cells (NFκB), apoptosis of immune cells, epigenetics, and microRNAs (miRNAs). These mechanisms interconnect ET with chronic inflammatory diseases including periodontitis. While the direct correlation between ET and periodontal destruction has not been fully elucidated, emerging reports point towards the potential tolerization of human periodontal ligament cells (hPDLCs) and gingival tissues with a significant reduction of TLR levels. CONCLUSIONS: There is a potential link between ET and periodontal diseases. Future studies should explore the crucial role of ET in the pathogenesis of periodontal diseases, as evidence of a tolerized oral mucosa may represent an intrinsic mechanism capable of regulating the oral immune response. A clear understanding of this host immune regulatory mechanism might lead to effective and more predictable therapeutic strategies to treat chronic inflammatory diseases and periodontitis.

Mechanical removal of biofilm on titanium discs: An in vitro study.

The objective of this in vitro study was to evaluate surface cleanness and cytocompatibility following mechanical instrumentation of biofilm-contaminated titanium surfaces. Titanium discs (non-modified [Ti(s)] and shot-blasted surfaces [Ti(r)]) contaminated with Streptococcus gordonii were instrumented using four different techniques: (i) gauze soaked in saline (GS), (ii) ultra-sonic device (US), (iii) rotating nickel-titanium brush (TiB), or (iv) air-polishing device (AP). Non-contaminated, untreated titanium disks were used as controls (C). Residual deposits and cytocompatibility for osteoblast-like cells were evaluated using scanning electron microscopy, immunofluorescence, and reverse transcriptase polymerase chain reaction. While the number of residual bacteria on Ti(s) discs was close to 0 in all treatment groups, significantly higher mean numbers of residual bacteria were observed on Ti(r) discs for GS (152.7 ± 75.7) and TiB (33.5 ± 22.2) than for US (0) and AP (0). Instrumentation with US resulted in deposition of foreign material (mean area% of foreign material: 3.0 ± 3.6% and 10.8 ± 9.6% for Ti(s) and Ti(r) discs, respectively). AP was the most effective decontamination procedure in reducing bacteria without depositing residual foreign material on Ti(r) discs. TiB and AP were superior methods in restoring cytocompatibility, although no method of mechanical decontamination resulted in pristine levels of cytocompatibility.

In vitro evaluation of chemical decontamination of titanium discs.

Peri-implant diseases are caused by bacterial biofilm colonizing implant surfaces. Prevention and management of peri-implant mucositis and peri-implantitis rely on effective biofilm removal. This study aimed to evaluate biofilm removal and cytocompatibility following chemo-mechanical surface decontamination of biofilm-coated titanium discs. Biofilm-coated (Streptococcus gordonii) discs, with either non-modified (smooth) or modified (rough) surfaces, were instrumented using a sterile gauze soaked in one out of four solutions: saline (NaCl), alkaline electrized water (AEW), citric acid (CA) or N-acetyl-L-cysteine (NAC). Non-contaminated, untreated titanium discs served as controls (C). Residual deposits (bacteria and gauze fibers) and cytocompatibility for osteoblast-like cells were evaluated using SEM and immunofluorescence. Cytotoxicity was assessed using WST-8 assay and immunofluorescence. All protocols were equally effective in removing bacteria from smooth surfaces, while AEW and CA were found to be superior at rough surfaces. AEW and NAC were superior in promoting cytocompatibility over NaCl. NAC and CA had a strong cytotoxic effect on osteoblast-like and fibroblast cells. In conclusion, AEW may be beneficial in the decontamination of implant surfaces, effectively removing bacterial biofilm and restoring cytocompatibility.

Teaching for Student and Societal Wellbeing in HPE: Nine Pedagogies for Social Justice.

We currently find ourselves living in precarious times, with old and new social inequities on the rise due to the challenges associated with an unprecedented rise of global migration and neoliberalism, amplified in our post COVID-19 world. Research has demonstrated that there is a high correlation between inequality at the societal level and the overall health and wellbeing of individuals within those societies. We believe that school health and physical education (HPE) has a significant role to play in addressing and acting on social inequities that impact on the wellbeing of both students and society as a whole. Based on the findings of an international research project called EDUHEALTH which explored pedagogies for social justice in school health and physical education (HPE) across Sweden, Norway and New Zealand, this paper aims to highlight the addressing of (in)equality and student wellbeing through HPE practice. In particular, the paper presents nine different but complementary pedagogies for social justice that we believe can improve individual, collective, and societal wellbeing. We conclude by proposing that, if adopted across a whole school curriculum, these nine pedagogies for social justice could form the basis of a holistic school-wide community approach aimed at improving both student and societal wellbeing.

Epigenetic changes of osteoblasts in response to titanium surface characteristics.

We aimed to investigate the influence of titanium surface characteristics on epigenetic mechanisms and DNA damage/repair pathways. Osteoblast-like cells (MG63) were incubated on glass, smooth titanium, and minimally rough titanium discs, respectively, for 0, 1, 6, and 24 hr. The presence of double-stranded DNA damage (γH2AX), DNA repair (Chk2), and epigenetic markers (AcH3 & DNMT1) were investigated using immunofluorescence. There were no Chk2-positive cells on the minimally rough titanium surfaces at all-time points, in comparison to glass and smooth titanium. Total γH2AX-positive cells on minimally rough titanium gradually decreased as incubation time increased, on the contrary to smooth titanium. Minimally rough titanium surfaces induced cytoplasmic staining of DNMT1 up to 99% at 24 hr. For epigenetic markers related to the DNA damage/repair pathway, minimally rough titanium surfaces showed the lower percentage of AcH3-positive cells compared to glass and smooth titanium surface. The findings in the current study show that titanium surface characteristics indeed influence DNA damage and the DNA repair pathway, including epigenetic factors.

Immunohistological composition of peri-implantitis affected tissue around ceramic implants-A pilot study.

BACKGROUND: Aim of the pilot study was the histologic classification of the inflamed peri-implant soft tissue around ceramic implants (CI) in comparison with titanium implants (TI). METHODS: Peri-implant tissue were retrieved from 15 patients (aged 34 to 88 years, seven males/eight females) with severe peri-implantitis (eight CI, seven TI). The peri-implant soft tissue samples were retrieved from the sites during scheduled removal of the implant and prepared for immunohistochemical analysis. Monoclonal antibodies (targeting CD3, CD20, CD138, and CD68) were used to identify T- and B-cells, plasma cells and macrophages. Quantitative assessment was performed by one histologically trained investigator. Linear mixed regression models were used. RESULTS: A similar numerical distribution of the cell population was found in peri-implantitis around CI compared with TI. CD3 (TI, 17% to 85% versus CI, 20% to 70% of total cell number) and CD138 (TI, 1% to 73% versus CI, 12% to 69% of total cell number) were predominantly expressed. Notably, patient-individual differences of numerical cell distribution were detected. Co-localization of B- and T-lymphocytes was observed. CONCLUSIONS: Peri-implantitis around CI in comparison with TI seems to have a similar histological appearance. Differences in cellular composition of peri-implantitis lesions might also depend on the patient's specific immune status and not only on the material used.

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration-A Review.

The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better tissue regeneration? Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.

Cellular expression of DNA damage/repair and reactive oxygen/nitrogen species in human periodontitis and peri-implantitis lesions.

AIM OF THE STUDY: To evaluate differences in the cellular expression of DNA damage/repair and reactive oxygen/nitrogen species between human periodontitis and peri-implantitis lesions. MATERIAL AND METHODS: 40 patients presenting with generalized severe periodontitis and 40 patients with severe peri-implantitis were included. Soft tissue biopsies were collected from diseased sites in conjunction with surgical therapy and prepared for histological analysis. Four regions of interest were identified: the pocket epithelium (PE), the infiltrated connective tissue (ICT), which was divided into one inner area facing the PE (ICT-1) and one outer area (ICT-2). A non-infiltrated connective tissue area (NCT) lateral of the ICT was also selected. RESULTS: It was demonstrated that the ICT of peri-implantitis specimens was considerably larger and contained significantly larger area proportions and densities of CD68-, MPO- and iNOS-positive cells than that of periodontitis samples. Cellular densities were overall higher in the inner ICT zone lateral of the PE (ICT-1) than in the outer ICT compartment (ICT-2). While the NCT area lateral of the ICT comprised significantly larger proportions and densities of y-H2AX-, iNOS-, NOX2-, MPO- and PAD4/MPO-positive cells in peri-implantitis than in periodontitis sites, a reverse difference was noted for the area proportion and density of 8-OHdG-positive cells in the PE. CONCLUSIONS: It is suggested that peri-implantitis lesions are associated with an enhanced and upregulated host response and contain larger numbers of neutrophils, macrophages and iNOS-positive cells than periodontitis lesions.

Social Justice Pedagogies in School Health and Physical Education-Building Relationships, Teaching for Social Cohesion and Addressing Social Inequities.

A focus on equity and social justice in school health and physical education (HPE) is pertinent in an era where there are growing concerns about the impact of neoliberal globalization and the precariousness of society. The aim of the present study was to identify school HPE teaching practices that promote social justice and more equitable health outcomes. Data were generated through 20 HPE lesson observations and post-lesson interviews with 13 HPE teachers across schools in Sweden, Norway, and New Zealand. The data were analysed following the principles of thematic analysis. In this paper, we present and discuss findings related to three overall themes: (i) relationships; (ii) teaching for social cohesion; (iii) and explicitly teaching about, and acting on, social inequities. Collectively, these themes represent examples of the enactment of social justice pedagogies in HPE practice. To conclude, we point out the difficulty of enacting social justice pedagogies and that social justice pedagogies may not always transform structures nor make a uniform difference to all students. However, on the basis of our findings, we are reaffirmed in our view that HPE teachers can make a difference when it comes to contributing to more socially just and equitable outcomes in HPE and beyond.