Medications for attention deficit hyperactivity disorder associated with increased risk of developing glaucoma.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) therapies including atomoxetine, methylphenidate, and amphetamines are some of the most prescribed medications in North America. Due to their sympathomimetic action, these drugs are contraindicated in patients with a history of angle closure glaucoma (ACG). This study aims to determine the risk of ACG and open angle glaucoma (OAG) among users of these treatments. METHODS: This is a retrospective cohort study with a case control analysis using the PharMetrics Plus Database (IQVIA, USA). We created a cohort of new users of atomoxetine, methylphenidate, and amphetamines and they were followed to the first diagnosis of (1) ACG or OAG; or (2) end of follow up. For each case, four age-matched controls were selected. A conditional logistic regression model was used to adjust for confounders and to calculate adjusted incidence-rate-ratios (aIRRs). RESULTS: A total of 240,257 new users of the ADHD medications were identified. The mean age was 45.0 ± 19.4 years and 55% of the cohort was female. Regular users of atomoxetine and amphetamines had a higher aIRR for developing ACG compared with non-users (aIRR = 2.55 95% CI [1.20-5.43] and 2.27 95% CI [1.42-3.63], respectively); while users of methylphenidate had a higher aIRR for developing OAG (aIRR = 1.23 95% CI [1.05-1.59]). CONCLUSIONS: Use of amphetamines and atomoxetine had a higher risk for ACG, while use of methylphenidate was associated with a higher risk for OAG. Given the prevalence of ADHD medication use (medically and recreationally), our current data on their associated risk of glaucoma have profound public health implications.

Ab interno trabeculectomy revision with 5-flourouracil for failed trabeculectomy in advanced glaucoma: 3-year outcomes.

OBJECTIVE: To describe the 3-year outcomes of patients who underwent ab interno trabeculectomy revision with a translimbal sclerostomy spatula augmented with 5-flourouracil. DESIGN: Retrospective cohort study. PARTICIPANTS: In this single-centre study, inclusion criteria included patients who were 18 years of age or older with advanced glaucoma who had undergone ab interno trabeculectomy revision with 5-flourouracil due to subconjunctival fibrosis and above-target intraocular pressure (IOP). Patients were required to have a minimum follow-up of 3 years. METHODS: The primary outcome measure was IOP. Secondary outcome measures included number of topical IOP-lowering medications, best-corrected distance visual acuity, visual field mean deviation, and postoperative complications. RESULTS: Forty-one eyes of 41 patients met the criteria for inclusion. Survival analysis demonstrated success defined by criterion A (IOP <15 mm Hg and >20% reduction) in 44% of eyes without medication (complete success) and 71% of eyes with or without medication (qualified success) at 3-year follow-up. Complete and qualified successes defined by criterion B (IOP <12 mm Hg and >20% reduction) were achieved by 31% and 44% of eyes, respectively. Early complications included transient hypotony in 26 eyes (63%) and transient hyphema in 3 eyes (7.3%). No persistent complications were reported within the 3-year study period. CONCLUSION: Ab interno trabeculectomy revision can be an effective technique for achieving a low target IOP in patients with advanced glaucoma in up to 3-year follow-up.

Personal Hypoxia Symptoms Vary Widely Within Individuals.

INTRODUCTION: Exposure to high ambient altitudes above 10,000 ft (3048 m) over sea level during aviation can present the risk of hypobaric hypoxia. Hypoxia can impair sensory and cognitive functions, degrading performance and leading to mishaps. Military aircrew undergo regular hypoxia familiarization training to recognize their symptoms and understand the consequences of hypoxia. However, over the years, aviators have come to believe that individuals have a "personal hypoxia signature." The idea is that intraindividual variability in symptom experience during repeated exposure is low. In other words, individuals will experience the same symptoms during hypoxia from day to day, year to year.METHODS: We critically reviewed the existing literature on this hypothesis. Most studies that claim to support the notion of a signature only examine group-level data, which do not inform individual-level consistency. Other studies use inappropriate statistical methods, while still others do not control for accuracy of recall over the period of years. To combat these shortcomings, we present a dataset of 91 individuals who completed nearly identical mask-off, normobaric hypoxia exposures days apart.RESULTS: We found that for every symptom on the Hypoxia Symptom Questionnaire, at least half of the subjects reported the symptom inconsistently across repeated exposure. This means that, at best, 50% of subjects did not report the same symptom across exposures.DISCUSSION: These data provide compelling evidence against the existence of hypoxia signatures. We urge that hypoxia familiarization training incorporate these findings and encourage individuals to expect a wide range of hypoxia symptoms upon repeated exposure.Cox BD, McHail DG, Blacker KJ. Personal hypoxia symptoms vary widely within individuals. Aerosp Med Hum Perform. 2024; 95(1):54-58.

A unique case of glaucoma associated with heterotopic bone formation in the anterior chamber angle.

Purpose: To describe a unique case of unilateral open angle glaucoma secondary to heterotopic bone formation in the anterior chamber angle. Observations: A 57 year-old male with an unremarkable history presented with right eye pain. Anterior segment examination demonstrated a solid, white deposit overlying the trabecular meshwork and peripheral iris associated with an intraocular pressure of 44 mmHg. The left eye examination was unremarkable. Biopsy of the material surprisingly showed heterotopic bone. Removal of the material and medical treatment were unable to adequately control the intraocular pressure and a trabeculectomy was successfully performed. Conclusions and Importance: This case demonstrates a unique cause of secondary open angle glaucoma: heterotopic bone formation in the anterior chamber angle.

PreserFlo Microshunt for the management of intraocular pressure elevation in iridocorneal endothelial syndrome.

Purpose: To report on a case of angle-closure glaucoma secondary to iridocorneal endothelial (ICE) syndrome effectively managed with the PreserFlo Microshunt. Observations: We report successful implantation of a PreserFlo Microshunt in a 57-year-old patient with secondary angle-closure glaucoma in the context of ICE syndrome. Following failure of medical therapy to adequately control intraocular pressure (IOP), the patient was consented for surgical intervention and underwent combined cataract surgery and PreserFlo Microshunt implantation. IOP at the last post-operative follow-up (5 months) was 12 mmHg with the patient on brinzolamide/timolol maleate (Azarga®). We report no complications in the post-operative period. Conclusions and importance: The PreserFlo Microshunt may be a promising option for patients with ICE syndrome who fail medical therapy. Implantation of this device was well tolerated in the presented case.

Examining the Effect of Income-Based Inequalities and Dental Service Provision on Dental Service Utilization among Older Australians: A Multiple Mediation Analysis.

INTRODUCTION: Public service provision is one of the keys to reducing inequalities in the utilization of dental services. Given the increase in the aging population, there should be a focus on older adults' oral health. However, this is often overlooked. OBJECTIVES: This study investigates the effectiveness of public services in reducing income-related inequalities in dental service utilization among older South Australians. METHODS: A multiple counterfactual mediation analysis using the ratio of mediator probability weighting approach was used to explore the proposed mediation mechanism using a South Australian population of older adults (≥65 y). The exposure variable in the analysis was income, and the mediators were concession cards and the last dental sector (public or private). The outcome variable was the time of last dental visit. RESULTS: Half of the older adults with high income (≥$40,000) owned a concession card, and 10% of those who attended public dental services belonged to this group. Interestingly, only 16.3% of the study participants had visited the public dental sector at their last dental appointment. Results showed a negligible indirect effect (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.85-1.05) and a significant direct effect (OR, 3.09; 95% CI, 2.24-4.87). By changing the potential outcome distributions to the counterfactual exposure distributions and taking the mediators' distribution as a counterfactual exposure distribution, the odds of dental visits occurring before the past 12 mo approximately tripled for low-income compared to high-income individuals. CONCLUSION: Income inequalities were associated with relatively delayed dental visits in older South Australians, and provision of public services could not improve this pattern. This might happen due to inequitable access to concession cards and public services. A review of policies is required, including addressing income inequalities and implementing short-term approaches to improve service utilization patterns in older South Australians. KNOWLEDGE TRANSFER STATEMENT: The findings of this study can enable policymakers for informed decision-making about the provision of public dental services for older Australians. This study emphasizes the importance of reviewing the current public dental services and subsidies and implementing short-term approaches to reduce income inequalities for older Australians.

Mechanistic Evidence of a Ni(0/II/III) Cycle for Nickel Photoredox Amide Arylation.

This work demonstrates the dominance of a Ni(0/II/III) cycle for Ni-photoredox amide arylation, which contrasts with other Ni-photoredox C-heteroatom couplings that operate via Ni(I/III) self-sustained cycles. The kinetic data gathered when using different Ni precatalysts supports an initial Ni(0)-mediated oxidative addition into the aryl bromide. Using NiCl2 as the precatalyst resulted in an observable induction period, which was found to arise from a photochemical activation event to generate Ni(0) and to be prolonged by unproductive comproportionation between the Ni(II) precatalyst and the in situ generated Ni(0) active species. Ligand exchange after oxidative addition yields a Ni(II) aryl amido complex, which was identified as the catalyst resting state for the reaction. Stoichiometric experiments showed that oxidation of this Ni(II) aryl amido intermediate was required to yield functionalized amide products. The kinetic data presented supports a rate-limiting photochemically-mediated Ni(II/III) oxidation to enable C-N reductive elimination. An alternative Ni(I/III) self-sustained manifold was discarded based on EPR and kinetic measurements. The mechanistic insights uncovered herein will inform the community on how subtle changes in Ni-photoredox reaction conditions may impact the reaction pathway, and have enabled us to include aryl chlorides as coupling partners and to reduce the Ni loading by 20-fold without any reactivity loss.

Deciphering the tumour immune microenvironment cell by cell.

Immune checkpoint inhibitors (ICIs) have rejuvenated therapeutic approaches in oncology. Although responses tend to be durable, response rates vary in many cancer types. Thus, the identification and validation of predictive biomarkers is a key clinical priority, the answer to which is likely to lie in the tumour microenvironment (TME). A wealth of data demonstrates the huge impact of the TME on ICI response and resistance. However, these data also reveal the complexity of the TME composition including the spatiotemporal interactions between different cell types and their dynamic changes in response to ICIs. Here, we briefly review some of the modalities that sculpt the TME, in particular the metabolic milieu, hypoxia and the role of cancer-associated fibroblasts. We then discuss recent approaches to dissect the TME with a focus on single-cell RNA sequencing, spatial transcriptomics and spatial proteomics. We also discuss some of the clinically relevant findings these multi-modal analyses have yielded.

Non-arteritic anterior ischemic and glaucomatous optic neuropathy: Implications for neuroretinal rim remodeling with disease severity.

PURPOSE: Post-acute non-arteritic ischemic optic neuropathy (NAION) and glaucomatous optic neuropathy (GON) can be difficult to differentiate clinically. Our objective was to identify optical coherence tomography (OCT) parameters to help differentiate these optic neuropathies. METHODS: We compared 12 eyes of 8 patients with NAION and 12 eyes of 12 patients with GON, matched for age and visual field mean deviation (MD). All patients underwent clinical assessment, automated perimetry (Humphrey Field Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA), and OCT imaging (Spectralis OCT2; Heidelberg Engineering, Heidelberg, Germany) of the optic nerve head and macula. We derived the neuroretinal minimum rim width (MRW), peripapillary retinal nerve fibre layer (RNFL) thickness, central anterior lamina cribrosa depth, and macular retinal thickness. RESULTS: MRW was markedly thicker, both globally and in all sectors, in the NAION group compared to the GON group. There was no significant group difference in RFNL thickness, globally or in any sector, with the exception of the temporal sector that was thinner in the NAION group. The group difference in MRW increased with increasing visual field loss. Other differences observed included lamina cribrosa depth significantly greater in the GON group and significantly thinner central macular retinal layers in the NAION group. The ganglion cell layer was not significantly different between the groups. CONCLUSIONS: The neuroretinal rim is altered in a dissimilar manner in NAION and GON and MRW is a clinically useful index for differentiating these two neuropathies. The fact that the difference in MRW between the two groups increased with disease severity suggests distinct remodelling patterns in response to differing insults with NAION and GON.

Dental enamel defects and dental caries of primary teeth among Indigenous children in Western Australia.

BACKGROUND: Teeth affected with enamel defects (EDs) are at an increased risk of dental caries. In spite of improving oral health status overall in Australia, Indigenous Australians still experience higher rates of dental caries than non-Indigenous Australians. This study reports on the prevalence of EDs and dental caries experience among Indigenous children in the Kimberley region of Western Australia. METHODS: Health status of all the primary teeth (ICDAS II criteria) and the presence of EDs on index teeth (modified Dental Defects of Enamel index; DDE) of young Indigenous children who participated in a 2-arm intervention trial was recorded. Generalized estimating equations were used to estimate the association between EDs and dental caries and effect estimates were presented as odds ratios and associated 95% confidence intervals. RESULTS: Person-level prevalence, from 237 children (mean age 3.6 years, standard deviation 1.7) assessed for EDs, was 58% and tooth-level prevalence was 24%. Teeth affected with demarcated or diffuse defects were associated with a twofold higher odds of having caries experience, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.7-3.7 and OR 2.7, 95% CI 1.7-4.0 respectively. CONCLUSIONS: The presence of EDs among young Indigenous children was associated with a higher odds of caries experience among affected teeth.

Efficacy and safety of ab interno trabeculectomy revision with 5-fluorouracil in advanced glaucoma due to subconjunctival fibrosis.

OBJECTIVE: To describe the outcomes of patients who underwent a single ab interno trabeculectomy revision augmented with 5-fluorouracil. DESIGN: Retrospective cohort study. PARTICIPANTS: All patients who had undergone ab interno trabeculectomy revision at a single tertiary care centre during the 5-year study period. All patients had advanced glaucomatous optic neuropathy, and all treated ages and glaucoma subtypes were included. METHODS: Outcome measures included surgical success, number of topical intraocular pressure (IOP)-lowering drops, best-corrected visual acuity, visual field mean deviation, and postoperative complications. Success at 12 months was defined using 2 criteria: criterion A (IOP <15 mm Hg and >20% reduction) and criterion B (IOP <12 mm Hg and >20% reduction). Each success criterion was subdivided into patients who achieved success without topical IOP-lowering drops (complete success) or with topical therapy (qualified success). RESULTS: This study included 46 eyes of 46 patients. Of these, 34 patients were followed for 12 months or more to assess surgical success. Success defined by criterion A was achieved by 68% of these 34 patients (53% complete, 15% qualified). Success defined by criterion B was achieved by 47% of these patients (38% complete, 9% qualified). Early hypotony was noted in 68% of eyes but was not associated with negative visual acuity or visual field outcomes. CONCLUSIONS: An IOP of <12 mm Hg and a >20% IOP reduction were achieved by 47% of patients overall (with or without topical therapy) at 12 months of follow-up. Transient early postoperative hypotony should be expected following ab interno revision trabeculectomy.

CD47-SIRPα axis blockade in NASH promotes necroptotic hepatocyte clearance by liver macrophages and decreases hepatic fibrosis.

Necroptosis contributes to hepatocyte death in nonalcoholic steatohepatitis (NASH), but the fate and roles of necroptotic hepatocytes (necHCs) in NASH remain unknown. We show here that the accumulation of necHCs in human and mouse NASH liver is associated with an up-regulation of the "don't-eat-me" ligand CD47 on necHCs, but not on apoptotic hepatocytes, and an increase in the CD47 receptor SIRPα on liver macrophages, consistent with impaired macrophage-mediated clearance of necHCs. In vitro, necHC clearance by primary liver macrophages was enhanced by treatment with either anti-CD47 or anti-SIRPα. In a proof-of-concept mouse model of inducible hepatocyte necroptosis, anti-CD47 antibody treatment increased necHC uptake by liver macrophages and inhibited markers of hepatic stellate cell (HSC) activation, which is responsible for liver fibrogenesis. Treatment of two mouse models of diet-induced NASH with anti-CD47, anti-SIRPα, or AAV8-H1-shCD47 to silence CD47 in hepatocytes increased the uptake of necHC by liver macrophages and decreased markers of HSC activation and liver fibrosis. Anti-SIRPα treatment avoided the adverse effect of anemia found in anti-CD47-treated mice. These findings provide evidence that impaired clearance of necHCs by liver macrophages due to CD47-SIRPα up-regulation contributes to fibrotic NASH, and suggest therapeutic blockade of the CD47-SIRPα axis as a strategy to decrease the accumulation of necHCs in NASH liver and dampen the progression of hepatic fibrosis.

Identification of Natural Product Sulfuretin Derivatives as Inhibitors for the Endoplasmic Reticulum Redox Protein ERO1α.

The flavin adenine dinucleotide containing Endoplasmic Reticulum Oxidoreductase-1 α (ERO1α) catalyzes the formation of de novo disulfide bond formation of secretory and transmembrane proteins and contributes towards proper protein folding. Recently, increased ERO1α expression has been shown to contribute to increased tumor growth and metastasis in multiple cancer types. In this report we sought to define novel chemical space for targeting ERO1α function. Using the previously reported ERO1α inhibitor compound, EN-460, as a benchmark pharmacological tool we were able to identify a sulfuretin derivative, T151742 which was approximately two-fold more potent using a recombinant enzyme assay system (IC50 = 8.27 ± 2.33 µM) compared to EN-460 (IC50= 16.46 ± 3.47 µM). Additionally, T151742 (IC50 = 16.04 µM) was slightly more sensitive than EN-460 (IC50= 19.35µM) using an MTT assay as an endpoint. Utilizing a cellular thermal shift assay (CETSA), we determined that the sulfuretin derivative T151742 demonstrated isozyme specificity for ERO1α as compared to ERO1ß and showed no detectable binding to the FAD containing enzyme LSD-1. T151742 retained activity in PC-9 cells in a clonogenicity assay while EN-460 was devoid of activity. Furthermore, the activity of T151742 inhibition of clonogenicity was dependent on ERO1α expression as CRISPR edited PC-9 cells were resistant to treatment with T151742. In summary we identified a new scaffold that shows specificity for ERO1α compared to the closely related paralog ERO1ß or the FAD containing enzyme LSD-1 that can be used as a tool compound for inhibition of ERO1α to allow for pharmacological validation of the role of ERO1α in cancer.

Access to dental care barriers and poor clinical oral health in Australian regional populations.

BACKGROUND: This paper investigated the associations between oral health with behavioural, demographic, periodontitis risk, financial and access to dental care barriers and compared the results in three Australian regional areas. METHODS: Data were obtained from the Australian National Study of Adult Oral Health (2017-18). Oral health status was measured using DMFT-score, and mean numbers of decayed, missing or filled teeth and periodontitis prevalence using the Center for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP) Periodontal Classification. The analysis included these dependent variables by three regional areas, seven socio-demographic variables, two periodontal disease risk factors, two preventive dental behaviours, two barriers to dental care and three access to dental care variables. RESULTS: Of the 15,731 people interviewed, 5,022 were examined. There was no significant difference in periodontitis prevalence between the regions. All the socio-demographic characteristics, periodontal disease risk factors and preventive dental behaviours were significantly associated with at least one of the dental caries indicators. In multivariable analysis, there was no significant association between regional location with any of the four clinical dental caries variables. CONCLUSION: Poorer oral health outside major cities was associated with household income, education level, higher smoking, usual reason for and frequency of dental visiting.

Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution.

Efferocytosis, the clearance of apoptotic cells (ACs) by macrophages, is critical for tissue resolution, with defects driving many diseases. Mechanisms of efferocytosis-mediated resolution are incompletely understood. Here, we show that AC-derived methionine regulates resolution through epigenetic repression of the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphatase Dusp4. We focus on two key efferocytosis-induced pro-resolving mediators, prostaglandin E2 (PGE2) and transforming growth factor beta 1 (TGF-ß1), and show that efferocytosis induces prostaglandin-endoperoxide synthase 2/cyclooxygenase 2 (Ptgs2/COX2), leading to PGE2 synthesis and PGE2-mediated induction of TGF-ß1. ERK1/2 phosphorylation/activation by AC-activated CD36 is necessary for Ptgs2 induction, but this is insufficient owing to an ERK-DUSP4 negative feedback pathway that lowers phospho-ERK. However, subsequent AC engulfment and phagolysosomal degradation lead to Dusp4 repression, enabling enhanced p-ERK and induction of the Ptgs2-PGE2-TGF-ß1 pathway. Mechanistically, AC-derived methionine is converted to S-adenosylmethionine, which is used by DNA methyltransferase-3A (DNMT3A) to methylate Dusp4. Bone-marrow DNMT3A deletion in mice blocks COX2/PGE2, TGF-ß1, and resolution in sterile peritonitis, apoptosis-induced thymus injury and atherosclerosis. Knowledge of how macrophages use AC-cargo and epigenetics to induce resolution provides mechanistic insight and therapeutic options for diseases driven by impaired resolution.

Investigating a clinically actionable BRAF mutation for monitoring low-grade serous ovarian cancer: A case report.

Low-grade serous ovarian cancer (LGSOC) poses a specific clinical challenge due to advanced presentation at diagnosis and the lack of effective systemic treatments. The aim of this study was to use a precision medicine approach to identify clinically actionable mutations in a patient with recurrent LGSOC. Primary, metastatic and recurrence tissue, and blood samples were collected from a stage IV LGSOC patient. Single-gene testing for clinically actionable mutations (BRAF V600, KRAS and NRAS) and subsequent whole-exome sequencing (WES) were performed. Droplet digital PCR was used to evaluate the presence of an identified BRAF D594G mutation in the matched plasma cell-free DNA (cfDNA). No clinically actionable mutations were identified using single-gene testing. WES identified a BRAF D594G mutation in six of seven tumor samples. The patient was commenced on a MEK inhibitor, trametinib, but with minimal clinical response. A newly designed ddPCR assay detected the BRAF alteration in the matched tissues and liquid biopsy cfDNA. The identification and sensitive plasma detection of a common "druggable" target emphasises the impact of precision medicine on the management of rare tumors and its potential contribution to novel monitoring regimens in this field.

Inequality and Inequity in the Use of Oral Health Services in Australian Adults.

OBJECTIVE: Social determinants drive disparities in dental visiting. This study aimed to measure inequality and inequity in dental visiting among Australian adults. METHODS: Data were obtained from the National Study of Adult Oral Health (2017 to 2018). Participants were Australian adults aged ≥30 y. The outcome of interest was dental visiting in the last 12 mo. Disparity indicators included education and income. Other sociodemographic characteristics included age, gender, Indigenous status, main language, place of birth, residential location, health card and dental insurance status, and individual's self-rated and impaired oral health. To characterize inequality in dental service use, we examined bivariate relationships using indices of inequality: the absolute and relative concentration indexes and the slope and relative indexes of inequality. Inequalities were depicted through concentration curves. Indirect standardization with a nonlinear model was used to measure inequity. RESULTS: A total of 9,919 Australian adults were included. Bivariate analysis showed a gradient by education and income on dental visiting, with 48% of those with lowest educational attainment/income having not visited a dentist in the last 12 mo. The concentration curves showed pro-low education and pro-poor income inequalities. All measures of absolute and relative indices were negative, indicating that from the bottom to the top of the socioeconomic ladder (education and income), the prevalence of no dental visiting decreased: absolute and relative concentration index estimates were approximately 2.5% and 5.0%, while the slope and relative indexes of inequality estimates were 14% to 18% and 0.4%, respectively. After need standardization, the group with the highest education or income had almost 1.5-times less probability of not having a dental visit in the previous year than those with the lowest education or income. CONCLUSION: The use of oral health services exhibited socioeconomic inequalities and inequities, disproportionately burdening disadvantaged Australian adults. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by policy makers when planning a dental labor force in relation to the capacity of supply dental services to 1) reduce the inequality and inequity in the use of oral health services and 2) meet identified oral health needs across the Australian population, which is important for preventive dental care.

Efferocytosis induces macrophage proliferation to help resolve tissue injury.

Apoptotic cell clearance by macrophages (efferocytosis) promotes resolution signaling pathways, which can be triggered by molecules derived from the phagolysosomal degradation of apoptotic cells. We show here that nucleotides derived from the hydrolysis of apoptotic cell DNA by phagolysosomal DNase2a activate a DNA-PKcs-mTORC2/Rictor pathway that increases Myc to promote non-inflammatory macrophage proliferation. Efferocytosis-induced proliferation expands the pool of resolving macrophages in vitro and in mice, including zymosan-induced peritonitis, dexamethasone-induced thymocyte apoptosis, and atherosclerosis regression. In the dexamethasone-thymus model, hematopoietic Rictor deletion blocked efferocytosing macrophage proliferation, apoptotic cell clearance, and tissue resolution. In atherosclerosis regression, silencing macrophage Rictor or DNase2a blocked efferocyte proliferation, apoptotic cell clearance, and plaque stabilization. In view of previous work showing that other types of apoptotic cell cargo can promote resolution in individual efferocytosing macrophages, the findings here suggest that signaling-triggered apoptotic cell-derived nucleotides can amplify this benefit by increasing the number of these macrophages.

Oral health changes among Indigenous and non-Indigenous Australians: findings from two national oral health surveys.

BACKGROUND: Historically, Indigenous Australians experienced poorer oral health than non-Indigenous Australians. We aimed to ascertain if Indigenous Australian oral health improved relative to non-Indigenous oral health between the 2004-06 and 2017-18 National Surveys of Adult Oral Health (NSAOH). METHODS: Both NSAOHs were population-based cross-sectional surveys of Australian adults aged 15 years or more. In both surveys, representative samples of adults were drawn through a three-stage, stratified sample design within metropolitan and regional areas in each state/territory. Frequencies of Indigenous and non-Indigenous self-reported and clinical oral health variables were ascertained, and differences were calculated between the 2004-06 and 2017-18 NSAOHs. Ninety-five per cent confidence intervals were calculated and weights were used to account for the complex sampling methodology of both surveys. RESULTS: In 2004-06, 229 Indigenous and 13 882 non-Indigenous Australians provided self-report data, and 87 and 5418 of these had dental examinations, respectively. In 2017-18, 334 Indigenous and 15 392 non-Indigenous Australians provided self-report data, and 84 and 4937 of them had dental examinations respectively. Between the surveys, relative to their non-Indigenous counterparts, Indigenous Australians experienced greater levels of: inadequate dentition (4.2%), experience of toothache (4.8%), problem-based dental attendance (4.5%) and 1+ teeth decayed, missing or filled (4.4%). CONCLUSIONS: The gap between poor self-reported and clinical oral health between Indigenous and non-Indigenous Australians was greater in the more recent survey.