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Periodontal considerations during orthodontic intrusion and extrusion in healthy and reduced periodontium.
In patients with advanced periodontal disease, pathological tooth migration may occur, which may require subsequent orthodontic treatment for both aesthetic and functional purposes. When planning orthodontic treatment mechanics, intrusive or extrusive forces are frequently indicated. Understanding tissue reactions during these movements is essential for clinicians when devising a comprehensive orthodontic-periodontal treatment plan. This knowledge enables clinicians to be fully aware of and account for the potential effects on the surrounding tissues. The majority of our understanding regarding the behavior of periodontal tissues in both healthy and compromised periodontal conditions is derived from animal studies. These studies offer the advantage of conducting histological and other assessments that would not be feasible in human research. Human studies are nevertheless invaluable in being able to understand the clinically relevant response elicited by the periodontal tissues following orthodontic tooth movement. Animal and human data show that in dentitions with reduced periodontal support, orthodontic intrusion of the teeth does not induce periodontal damage, provided the periodontal tissues do not have inflammation and plaque control with excellent oral hygiene is maintained. On the contrary, when inflammation is not fully controlled, orthodontic intrusion may accelerate the progression of periodontal destruction, with bacterial plaque remnants being displaced subgingivally, leading to further loss of attachment. Orthodontic extrusion, on the other hand, does not seem to cause further periodontal breakdown in dentitions with reduced periodontal support, even in cases with deficient plaque control. This is attributed to the nature of the tooth movement, which directs any plaque remnants coronally (supragingivally), reducing the risk of adverse effects on the periodontal tissues. This specific type of tooth movement can be leveraged to benefit periodontal conditions by facilitating the regeneration of lost hard and soft periodontal tissues in a coronal direction. As a result, orthodontic extrusion can be employed in implant site development, offering an advantageous alternative to more invasive surgical procedures like bone grafting. Regardless of the tooth movement prescribed, when periodontal involvement is present, it is essential to prioritize periodontal therapy before commencing orthodontic treatment. Adequate plaque control is also imperative for successful outcomes. Additionally, utilizing light orthodontic forces is advisable to achieve efficient tooth movement while minimizing the risk of adverse effects, notably root resorption. By adhering to these principles, a more favorable and effective combined orthodontic-periodontal approach can be ensured. The present article describes indications, mechanisms, side effects, and histological and clinical evidence supporting orthodontic extrusion and intrusion in intact and reduced periodontal conditions
Global and Regional Cardiovascular Mortality Attributable to Nonoptimal Temperatures Over Time.
BACKGROUND
The association between nonoptimal temperatures and cardiovascular mortality risk is recognized. However, a comprehensive global assessment of this burden is lacking.
OBJECTIVES
The goal of this study was to assess global cardiovascular mortality burden attributable to nonoptimal temperatures and investigate spatiotemporal trends.
METHODS
Using daily cardiovascular deaths and temperature data from 32 countries, a 3-stage analytical approach was applied. First, location-specific temperature-mortality associations were estimated, considering nonlinearity and delayed effects. Second, a multivariate meta-regression model was developed between location-specific effect estimates and 5 meta-predictors. Third, cardiovascular deaths associated with nonoptimal, cold, and hot temperatures for each global grid (55 km × 55 km resolution) were estimated, and temporal trends from 2000 to 2019 were explored.
RESULTS
Globally, 1,801,513 (95% empirical CI: 1,526,632-2,202,831) annual cardiovascular deaths were associated with nonoptimal temperatures, constituting 8.86% (95% empirical CI: 7.51%-12.32%) of total cardiovascular mortality corresponding to 26 deaths per 100,000 population. Cold-related deaths accounted for 8.20% (95% empirical CI: 6.74%-11.57%), whereas heat-related deaths accounted for 0.66% (95% empirical CI: 0.49%-0.98%). The mortality burden varied significantly across regions, with the highest excess mortality rates observed in Central Asia and Eastern Europe. From 2000 to 2019, cold-related excess death ratios decreased, while heat-related ratios increased, resulting in an overall decline in temperature-related deaths. Southeastern Asia, Sub-Saharan Africa, and Oceania observed the greatest reduction, while Southern Asia experienced an increase. The Americas and several regions in Asia and Europe displayed fluctuating temporal patterns.
CONCLUSIONS
Nonoptimal temperatures substantially contribute to cardiovascular mortality, with heterogeneous spatiotemporal patterns. Effective mitigation and adaptation strategies are crucial, especially given the increasing heat-related cardiovascular deaths amid climate change
Educational inequalities in multimorbidity at older ages: a multi-generational population-based study.
BACKGROUND
Social inequalities in multimorbidity may occur due to familial and/or individual factors and may differ between men and women. Using population-based multi-generational data, this study aimed to (1) assess the roles of parental and individual education in the risk of multimorbidity and (2) examine the potential effect modification by sex.
METHODS
Data were analysed from 62 060 adults aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 European countries. Intergenerational educational trajectories (exposure) were High-High (reference), Low-High, High-Low and Low-Low, corresponding to parental-individual educational attainments. Multimorbidity (outcome) was ascertained between 2013 and 2020 as self-reported occurrence of ≥2 diagnosed chronic conditions. Inequalities were quantified as multimorbidity-free years lost (MFYL) between the ages of 50 and 90 and estimated via differences in the area under the standardized cumulative risk curves. Effect modification by sex was assessed via stratification.
RESULTS
Low individual education was associated with higher multimorbidity risk regardless of parental education. Compared to the High-High trajectory, Low-High was associated with -0.2 MFYL (95% confidence intervals: -0.5 to 0.1), High-Low with 3.0 (2.4-3.5), and Low-Low with 2.6 (2.3-2.9) MFYL. This pattern was observed for both sexes, with a greater magnitude for women. This effect modification was not observed when only diseases diagnosed independently of healthcare-seeking behaviours were examined.
CONCLUSIONS
Individual education was the main contributor to intergenerational inequalities in multimorbidity risk among older European adults. These findings support the importance of achieving a high education to mitigate multimorbidity risk
Understanding Early Predictors and Inflammatory Markers for Mid-Term Outcomes in Laparoscopic Sleeve Gastrectomy.
Monitoring and control processes within executive functions: Is post-error slowing related to pre-error speeding in children?
Both pre-error speeding and post-error slowing reflect monitoring and control strategies. Post-error slowing is relatively well-established in children, whereas pre-error speeding is much less studied. Here we investigated (a) whether kindergarten and first-grade children show pre-error speeding in a cognitive control task (Hearts and Flowers) and, if so, (b) whether post-error slowing is associated with pre-error speeding. We analyzed the data from 153 kindergartners and 468 first-graders. Both kindergartners and first-graders showed significant pre-error speeding and post-error slowing, with no differences between the two samples in the magnitude of each. The magnitude of pre-error speeding and post-error slowing was correlated within individuals in both samples and to a similar extent. That is, children who sped up more extremely toward an error also slowed down more extremely after an error. These findings provide evidence that pre-error speeding and post-error slowing are related in children as early as kindergarten age and may in concert reflect how optimal children's monitoring and control of their performance is in a cognitive control task
An Archaeological Exploration of Prehistoric Land Use and Adaptations to Climate in the Southern Balkans
The Southern Balkans designate a region comprising the territories of North Macedonia, Albania and Greece. The landscape of this area was mainly created by tectonic activity and limestone weathering and is one of the geographically most diverse regions of Europe. It spreads from high altitude plains and lake systems to the Aegean Sea with its Mediterranean climate. Around 7000–6500 BC farming practises reached the Aegean Coast and subsequently spread into the European mainland in the millennia to follow. Here, farming and the involved societies under- went the adaptations which allowed them the further spread into the continent along different routes.
Radiocarbon data taken from archaeological contexts in the area show that after an initial phase, a wide range of diverse environmental zones on different elevations was settled. This means, people had adapted to different climatic conditions, possibly taking advantage from coinciding climate changes at the time. Archaeological evidence suggests unbroken presence of human activities in the Balkans until ca. 4000 BC, when the evidence for human activities sharply decreases. The phase coincides with maxima in forestation at least in parts of the region as suggested by independent sources. Only after 3500 BC a growing human presence connected to the Onset of the Early Bronze Age can be detected using radiocarbon dates.
During these early millenia of farming societies in the Balkans, several backlashes in human activities can be observed. These have been discussed to be connected to climate events, such as the 8.2 ka BP event at the onset of the Neolithic on the European mainland or the 4.2 ka event at the end of the Early Bronze Age. The aim of this poster is to discuss how the diachronically changing food systems might have been affected by these climatic impacts and what that might have meant for the involved societies. By exploring the respective subsistence economies and land use systems of the Neolithic and Bronze Age societies, probable resilience strategies or vulnerabilities facing climatic variability are discussed
Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial.
RATIONALE
Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery.
AIM AND HYPOTHESIS
To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo.
DESIGN
ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial.
PARTICIPANTS
610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living.
INTERVENTION
Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset.
COMPARISON
Matching placebo plus standardized rehabilitation.
OUTCOMES
The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events.
CONCLUSION
The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone
Complex mechanical loading and inflammation in intervertebral disc degeneration
Introduction
Intervertebral disc (IVD) degeneration is the cause of around half of all low back pain cases in young adults, however the initiating and risk factors are poorly understood, limiting development of personalized therapies. [1] Although the effects of pro-inflammatory cytokines and mechanical loading has been investigated within the IVD, [2] it is unknown how IVD response to complex mechanical loading is affected by the presence of cytokines. Thus, we aimed to investigate the combined effects of dynamic compression and torsion with catabolic cytokine interleukin 1 beta (IL-1β) and inhibitory cytokine interleukin 1 receptor antagonist (IL-1Ra), on bovine IVDs using ex vivo culture, magnetic resonance imaging (MRI), and finite element (FE) modeling.
Methods
Whole bovine IVDs obtained within 3-4 hours portmortem from a local abattoir were isolated and the IVDs cultured in a customized two degrees-of-freedom bioreactor applying diurnal dynamic compression (0.1-
0.5 MPa) and torsion (6°) under normal (HG DMEM), catabolic (10 ng/ml IL-1β) and inhibitory (10 ng/ml IL1Ra) media conditions for one week. Static compression (0.1 MPa) under the same media conditions were used as a control. Before and after culture, the IVDs were imaged using 3T MRI, which was used to create subjectspecific FE models. Downstream analyses included height measurement, qPCR, glycosaminoglycan (GAG) quantification, and cell metabolic activity. For statistical analysis (when n>3), nonparametric distribution was assumed and a Kruskal–Wallis test then Dunn’s multiple comparisons test were performed, and a P <
0.05 considered statistically significant.
Results
Following one week of culture, IVD height decreased in all conditions (Figure 1a & b), however, this disc height decreases was less pronounced within IVDs stimulated with IL-1Ra. Cellular metabolic activity in the nucleus pulposus (NP) decreased in all conditions, but the difference was only significant in IVDs stimulated with IL-1β and complex dynamic loading (Figure 1c). Similarly, the GAG content decreased in the NP of all conditions, but was not significant. Gene expression of anabolic genes, i.e. collagen type II (COL II) decreased (Figure 1e), while expression of catabolic genes, i.e. matrix metalloproteinase 3 (MMP3) increased in the NP tissue for all conditions except in control static IVDs and in IL-1Ra stimulated IVDs, respectively (Figure 1d). Introduction
Intervertebral disc (IVD) degeneration is the cause of around half of all low back pain cases in young adults, however the initiating and risk factors are poorly understood, limiting development of personalized therapies. [1] Although the effects of pro-inflammatory cytokines and mechanical loading has been investigated within the IVD, [2] it is unknown how IVD response to complex mechanical loading is affected by the presence of cytokines. Thus, we aimed to investigate the combined effects of dynamic compression and torsion with catabolic cytokine interleukin 1 beta (IL-1β) and inhibitory cytokine interleukin 1 receptor antagonist (IL-1Ra), on bovine IVDs using ex vivo culture, magnetic resonance imaging (MRI), and finite element (FE) modeling.
Methods
Whole bovine IVDs obtained within 3-4 hours portmortem from a local abattoir were isolated and the IVDs cultured in a customized two degrees-of-freedom bioreactor applying diurnal dynamic compression (0.1-
0.5 MPa) and torsion (6°) under normal (HG DMEM), catabolic (10 ng/ml IL-1β) and inhibitory (10 ng/ml IL1Ra) media conditions for one week. Static compression (0.1 MPa) under the same media conditions were used as a control. Before and after culture, the IVDs were imaged using 3T MRI, which was used to create subjectspecific FE models. Downstream analyses included height measurement, qPCR, glycosaminoglycan (GAG) quantification, and cell metabolic activity. For statistical analysis (when n>3), nonparametric distribution was assumed and a Kruskal–Wallis test then Dunn’s multiple comparisons test were performed, and a P <
0.05 considered statistically significant.
Results
Following one week of culture, IVD height decreased in all conditions (Figure 1a & b), however, this disc height decreases was less pronounced within IVDs stimulated with IL-1Ra. Cellular metabolic activity in the nucleus pulposus (NP) decreased in all conditions, but the difference was only significant in IVDs stimulated with IL-1β and complex dynamic loading (Figure 1c). Similarly, the GAG content decreased in the NP of all conditions, but was not significant. Gene expression of anabolic genes, i.e. collagen type II (COL II) decreased (Figure 1e), while expression of catabolic genes, i.e. matrix metalloproteinase 3 (MMP3) increased in the NP tissue for all conditions except in control static IVDs and in IL-1Ra stimulated IVDs, respectively (Figure 1d). Introduction
Intervertebral disc (IVD) degeneration is the cause of around half of all low back pain cases in young adults, however the initiating and risk factors are poorly understood, limiting development of personalized therapies. [1] Although the effects of pro-inflammatory cytokines and mechanical loading has been investigated within the IVD, [2] it is unknown how IVD response to complex mechanical loading is affected by the presence of cytokines. Thus, we aimed to investigate the combined effects of dynamic compression and torsion with catabolic cytokine interleukin 1 beta (IL-1β) and inhibitory cytokine interleukin 1 receptor antagonist (IL-1Ra), on bovine IVDs using ex vivo culture, magnetic resonance imaging (MRI), and finite element (FE) modeling.
Methods
Whole bovine IVDs obtained within 3-4 hours portmortem from a local abattoir were isolated and the IVDs cultured in a customized two degrees-of-freedom bioreactor applying diurnal dynamic compression (0.1-
0.5 MPa) and torsion (6°) under normal (HG DMEM), catabolic (10 ng/ml IL-1β) and inhibitory (10 ng/ml IL1Ra) media conditions for one week. Static compression (0.1 MPa) under the same media conditions were used as a control. Before and after culture, the IVDs were imaged using 3T MRI, which was used to create subjectspecific FE models. Downstream analyses included height measurement, qPCR, glycosaminoglycan (GAG) quantification, and cell metabolic activity. For statistical analysis (when n>3), nonparametric distribution was assumed and a Kruskal–Wallis test then Dunn’s multiple comparisons test were performed, and a P <0.05 considered statistically significant.
Results
Following one week of culture, IVD height decreased in all conditions (Figure 1a & b), however, this disc height decreases was less pronounced within IVDs stimulated with IL-1Ra. Cellular metabolic activity in the nucleus pulposus (NP) decreased in all conditions, but the difference was only significant in IVDs stimulated with IL-1β and complex dynamic loading (Figure 1c). Similarly, the GAG content decreased in the NP of all conditions, but was not significant. Gene expression of anabolic genes, i.e. collagen type II (COL II) decreased (Figure 1e), while expression of catabolic genes, i.e. matrix metalloproteinase 3 (MMP3) increased in the NP tissue for all conditions except in control static IVDs and in IL-1Ra stimulated IVDs, respectively (Figure 1d).Discussion
We hypothesized that catabolic cytokines, i.e. IL-1β, in the microenvironment of the IVD are sufficient to negatively alter the cellular response to complex loading, leading to further downstream degeneration. However, markers of degeneration were found in all conditions, which could indicate that loading was supraphysiological and catabolic alone. This will be investigated further using subject-specific FE models developed from the MRI images. Additionally, short half-lives of cytokines could have prevented them from diffusing through the IVD effectively, thus limiting the cellular response. This will be further investigated using immunohistochemistry and ELISA. Nevertheless, the results convey that static or complex dynamic loading is sufficient to induce catabolism with or without cytokine stimulation.
References
1. Baumgartner L et al., J. Int J Mol Sci. 2021; 22(2):703.
2. Walter BA et al., PLOS ONE. 2015; 10(3): e0118358.5
Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC.
BACKGROUND
Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive.
METHODS
A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3).
RESULTS
75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct.
CONCLUSION
CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging.
CLINICALTRIALS
gov number, NCT03318380
Assessing the perioperative gain of weight (Δweight) as a determinant of morbidity after kidney transplantation: a retrospective exploratory study.
Kidney transplantation (KT) is associated with a substantial risk of postoperative complications (POC) for which performant predictors are lacking. Data showed that a perioperative gain of weight (ΔWeight) was associated with higher risk of POC, but it remains unexplored in KT. This retrospective study aimed to investigate the association between ΔWeight and POC after KT. ΔWeight was calculated on postoperative day (POD) 2. POC were graded according to the Dindo-Clavien classification. Primary endpoint was overall POC. A total of 242 patients were included and 174 (71.9%) complications were reported. Patients showed a rapid gain of weight after KT. Mean ΔWeight was 7.83 kg (± 3.20) compared to 5.3 kg (± 3.56) in patients with and without complication, respectively (p = 0.0005). ΔWeight showed an accuracy of 0.74 for overall POC. A cut-off of 8.5 kg was determined. ΔWeight ≥ 8.5 kg was identified as an independent predictor of overall POC on multivariable analysis (OR 2.04; 95% CI 1.08-3.84; p = 0.025). ΔWeight ≥ 8.5 kg appeared as an independent predictor of POC after KT. These results stress the need to monitor weight in KT and to further investigate this surrogate with future studies assessing its clinical relevance