The promise and challenges of genomics-informed periodontal disease diagnoses.

Recent advances in human genomics and the advent of molecular medicine have catapulted our ability to characterize human and health and disease. Scientists and healthcare practitioners can now leverage information on genetic variation and gene expression at the tissue or even individual cell level, and an enormous potential exists to refine diagnostic categories, assess risk in unaffected individuals, and optimize disease management among those affected. This review investigates the progress made in the domains of molecular medicine and genomics as they relate to periodontology. The review summarizes the current evidence of association between genomics and periodontal diseases, including the current state of knowledge that approximately a third of the population variance of periodontitis may be attributable to genetic variation and the management of several monogenic forms of the disease can be augmented by knowledge of the underlying genetic cause. Finally, the paper discusses the potential utility of polygenic risk scores and genetic testing for periodontitis diagnosis now and in the future, in light of applications that currently exist in other areas of medicine and healthcare.

Minimally invasive non-surgical periodontal therapy of intrabony defects: A prospective multi-centre cohort study.

AIM: To assess the potential benefits of minimally invasive non-surgical therapy (MINST) in teeth with intrabony defects and to explore factors associated with the outcomes. MATERIALS AND METHODS: A multi-centre trial was conducted in 100 intrabony defects in periodontitis patients in private practice. Steps 1 and 2 periodontal therapy including MINST were provided. Clinical and radiographic data were analysed at baseline and 12 months after treatment, with the primary aim being change in radiographic defect depth at 12 months. RESULTS: Eighty-four patients completed the 12-month follow up. The mean total radiographic defect depth reduced by 1.42 mm and the defect angle increased by 3° (both p < .05). Statistically significant improvements in probing pocket depth (PPD) and clinical attachment level (CAL) were seen at 12 months compared to baseline (p < .001). Fifty-six defects (66.7%) achieved pocket closure (PPD ≤ 4 mm) and 49 defects (58.3%) achieved the composite outcome (PPD ≤ 4 mm and CAL gain ≥3 mm). Deeper and narrower angled defects were positively correlated with radiographic and clinical improvements, respectively. CONCLUSIONS: Improvements in clinical and radiographic outcomes were seen after MINST. This study highlights the generalizability and wide applicability of this approach, further supporting its effectiveness in the treatment of intrabony defects. CLINICAL TRIAL REGISTRATION: NCT03741374. https://clinicaltrials.gov/study/NCT03741374?cond=minimally%20invasive%20non%20surgical%20therapy&locStr=UK&country=United%20Kingdom&distance=50&rank=2.

The influence of assisted reproductive technologies-related stressors and social support on perceived stress and depression.

BACKGROUND: While assisted reproductive technologies (ART) have helped many people experiencing infertility become pregnant, the ART process can take a psychological toll. This study examined whether and how perceived stress- and depression-related symptoms vary among individuals at different stages of the infertility and ART process, and whether ART-specific stressors and emotional support are associated with mental health symptomatology. METHODS: Data were collected using an online REDCap survey administered between July 2021 and March 2022. The survey was administered to 240 participants who had experienced infertility, including those who had not yet accessed ART, those undergoing ART but who were not yet pregnant, those currently pregnant through ART, and those who had given birth in the last year through ART. Each participant completed the Cohen Perceived Stress Scale (range 0-40) and the Edinburgh Depression Scale (range 0-30). Participants who had undergone ART were asked about their experience of ART-specific stressors and how helpful partner and provider support had been during the ART process. Survey data were analyzed using ANOVA and multivariate linear regressions. RESULTS: 88% of participants reported medium or high levels of perceived stress, and 43.8% of respondents showed probable indications of depression. Perceived stress and depression symptoms were significantly higher for individuals currently undergoing, but not yet pregnant from, ART treatments. These effect sizes were substantial; for example, depression scores in this group were five points higher than among currently pregnant individuals and nine points higher than among postpartum individuals. For the subset of participants who had used or were currently undergoing ART (N = 221), perceived social stigma and the physical and time demands of ART were significantly associated with higher stress and depression symptoms, while partner emotional support was associated with lower perceived stress. CONCLUSIONS: The ART process exacerbates perceived stress and depression symptoms among individuals experiencing infertility. Given the potential long-term impacts on both parent and child wellbeing, clinicians and policymaking groups, including the American Society for Reproductive Medicine (ASRM), should consider making access to mental health services a standard of care during infertility treatment.

Vitamin D Deficiency, Chronic Kidney Disease and Periodontitis.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in the host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD) are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D, in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiological mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Scaffolding competence-based learning design in the dental simulation curriculum.

INTRODUCTION: Learning in a clinical domain in dentistry is complex and learners may face uncertain clinical scenarios. A simulation curriculum can be designed to have simple clinical scenarios and learning activities which progress in complexity and employ competence assessments of simulated clinical practice before students can undertake authentic practice on patients. This paper presents how scaffolding of competence can be used for designing learning with simulators (haptics and phantom head) demonstrated in a specific domain in restorative dentistry. METHODS: A collaborative workshop as a research approach was undertaken to inform the iterative analysis, development, and discussion on scaffolding the learning design with respect to competence assessments of learning cavity preparation with simulation-based learning technologies. A workshop was conducted, which was collaborative and involved design negotiations between researchers, technologists, and teachers/practitioners in developing the simulation curriculum. RESULTS: A competence assessment with feedback in a specific domain in preparing interproximal caries was used as a context to describe how the learning activities and outcomes were designed to meet assessment of competence with varied levels of simple to complex learning activities and structured sessions. CONCLUSION: Simulation curriculum can be designed and implemented by scaffolding the level of competence that can be learned using simulation between haptics and phantom-head. This brings impetus to the need in meeting the relevant competence criteria in context to a specific affordance of the simulation-based learning technologies to provide optimal patient-centred holistic care.

ASSOCIATION BETWEEN CALCIUM-CHANNEL BLOCKERS AND GINGIVAL ENLARGEMENT: A CASE-CONTROL STUDY.

OBJECTIVES: As reported by the existing literature, calcium-channel blockers (CCB) can lead to gingival enlargement. The aims of this study were to investigate the factors associated with gingival enlargement in patients on CCB and to assess the saliva and gingival crevicular fluid (GCF) profile of patients on CCB with gingival enlargement. METHODS: A total of 131 participants were included. Data were collected from 91 patients taking CCB for treatment of systemic hypertension. The presence of drug-induced gingival enlargement (DIGE) was assessed clinically and associated with patient factors. Patients with DIGE were group-matched for gender and ethnicity with an equal number of consecutive CCB non-DIGE patients (control 1), no-CCB no-DIGE (control 2) and periodontally healthy with no DIGE (control 3) for the saliva and GCF analysis. A bead-based multiplex immunoassay was used to assess a panel of biomarkers. RESULTS: Twenty-two per cent of patients on CCB were diagnosed with DIGE. Lack of daily interdental cleaning and self-reported diagnosis of type II diabetes were associated with the diagnosis of DIGE. When analysing patients only on CCB, those with DIGE had higher GCF levels of vascular endolthelial growth factor (VEGF) (p=0.032), epidermal growth factor (EGF) (p=0.030) and matrix metalloproteinase-8 (MMP-8) (p=0.008). Among the salivary markers, only MMP-8 showed a statistically significant difference across groups (p<0.001). CONCLUSIONS: This is the first study investigating saliva and GCF biomarkers in patients with DIGE and different control groups, suggesting that causes of the overgrowth might involve inflammatory processes, tissue damage pathways, and potentially an impact on growth factors like VEGF. Future research should verify these results in independent populations and explore the underlying pathogenic mechanisms in-depth. CLINICAL SIGNIFICANCE: Calcium-channel blockers (CCB) can lead to gingival enlargement. This study confirms lack of interdental cleaning and type II diabetes as risk factors. Elevated levels of VEGF, EGF, and MMP-8 in gingival crevicular fluid and MMP-8 in saliva suggest inflammatory processes and growth factors might play roles in this condition.

The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation.

Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by neuronal stimulation with brain-derived neurotrophic factor (BDNF), which results in eukaryotic initiation factor 2α (eIF2α) dephosphorylation and increases in de novo protein synthesis. Primary rodent neurons exposed to BDNF display elevated translation of GADD34, which facilitates eIF2α dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the integrated stress response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.

COVID-19 in the Initiation and Progression of Atherosclerosis: Pathophysiology During and Beyond the Acute Phase.

The incidence of atherosclerotic cardiovascular disease is increasing globally, especially in low- and middle-income countries, despite significant efforts to reduce traditional risk factors. Premature subclinical atherosclerosis has been documented in association with several viral infections. The magnitude of the recent COVID-19 pandemic has highlighted the need to understand the association between SARS-CoV-2 and atherosclerosis. This review examines various pathophysiological mechanisms, including endothelial dysfunction, platelet activation, and inflammatory and immune hyperactivation triggered by SARS-CoV-2 infection, with specific attention on their roles in initiating and promoting the progression of atherosclerotic lesions. Additionally, it addresses the various pathogenic mechanisms by which COVID-19 in the post-acute phase may contribute to the development of vascular disease. Understanding the overlap of these syndromes may enable novel therapeutic strategies. We further explore the need for guidelines for closer follow-up for the often-overlooked evidence of atherosclerotic cardiovascular disease among patients with recent COVID-19, particularly those with cardiometabolic risk factors.

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.