Single mandibular implant study - impact on dietary habits after 5 years of observation in patients with immediate and delayed loading protocols.

OBJECTIVES: Single midline implants in the edentulous mandible can be used to support existing complete dentures to improve patients' satisfaction and masticatory efficiency. The impact on patients' dietary habits and the influence of the loading protocol of the implants was the subject of this study. MATERIALS AND METHODS: In this prospective randomized clinical trial, edentulous patients with existing complete dentures in both jaws were treated with a single midline implant in the mandible. In group A, the implants were loaded immediately, in group B the loading was delayed after three months. Patients were asked to report on their nutritional intake before implant placement and 12, 24 and 60 months after loading using a standardized two-part questionnaire. RESULTS: Nutritional intake regarding the frequency of consumption of the requested food items did not change significantly during the 60-months study period, regardless of the loading protocol. In contrast, the second part of the questionnaire revealed that after 60 months, there was a significant decrease in avoidance of food, that had a coarse and hard texture in both groups. This significant decrease was observable in the group A in the first 12 and 24 months and in the group B after 60 months. CONCLUSION: A change in the patients' dietary habits due to the insertion of a single midline implant in the mandible to support the existing complete denture cannot be observed, independently to the loading protocol. CLINICAL RELEVANCE: Improving the chewing efficiency by single midline implants in the edentulous mandible does not lead to a change in dietary habits.

Influence of the Composition of Provisional Luting Materials on the Bond Strength of Temporary Single-Tooth Crowns on Titanium Abutments.

In addition to zinc oxide-based cements, resin-based materials are also available for temporary cementation. The aim of this in vitro study was to determine the influence of the different material compositions on temporary bonds. In nine test series (n = 30), temporary bis-acrylate single-tooth crowns were bonded onto prefabricated titanium abutments with nine different temporary luting materials. After simulating an initial (24 h, distilled water, 37 °C), a short-term (7 days, distilled water, 37 °C) and a long-term provisional restoration period (12h, distilled water, 37 °C; thermocycling: 5000 cycles) in subgroups (n = 10), the bond strength was examined using a combined tensile-shear test. Statistical analysis was performed by univariate analysis of variance or a non-parametric Kruskal-Wallis test, followed by post hoc tests. Of the three resin-based materials, two showed significantly higher bond strength values compared to all other materials (p < 0.001), regardless of the storage procedure. The resin-based materials were followed by eugenol-free and eugenol-containing zinc oxide materials. Significant intragroup differences were observed between the composite-based materials after all storage periods. This was only observed for some of the zinc oxide-based materials. The results show that under in vitro conditions, not only the composition of the temporary luting materials but also the different storage conditions have a significant influence on temporary bonds.

Skin-interfaced microfluidic biosensors for colorimetric measurements of the concentrations of ketones in sweat.

Ketones, such as beta-hydroxybutyrate (BHB), are important metabolites that can be used to monitor for conditions such as diabetic ketoacidosis (DKA) and ketosis. Compared to conventional approaches that rely on samples of urine or blood evaluated using laboratory techniques, processes for monitoring of ketones in sweat using on-body sensors offer significant advantages. Here, we report a class of soft, skin-interfaced microfluidic devices that can quantify the concentrations of BHB in sweat based on simple and low-cost colorimetric schemes. These devices combine microfluidic structures and enzymatic colorimetric BHB assays for selective and accurate analysis. Human trials demonstrate the broad applicability of this technology in practical scenarios, and they also establish quantitative correlations between the concentration of BHB in sweat and in blood. The results represent a convenient means for managing DKA and aspects of personal nutrition/wellness.

PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies.

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies.

Validating a Curvature-Based Marker of Cervical Carotid Tortuosity for Risk Assessment in Heritable Aortopathies.

BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies. METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). Logistic regression was performed to assess the likelihood of clinical end point according to baseline carotid tortuosity. Total absolute curvature at baseline was 11.13±5.76 and was relatively unchanged at 8 to 10 years (fold change: 0.026±0.298, P=1.00), whereas tortuosity index at baseline was 0.262±0.131, with greater variability at 8 to 10 years (fold change: 0.302±0.656, P=0.818). Baseline total absolute curvature correlated with aortic root diameter (r=0.456, P=0.004) and was independently associated with aortic events during the 4-year follow-up (adjusted odds ratio [OR], 2.64 [95% CI, 1.02-6.85]). Baseline tortuosity index correlated with age (r=0.532, P<0.001) and was not associated with events (adjusted OR, 1.88 [95% CI, 0.79-4.51]). Finally, baseline total absolute curvature had good discrimination of 4-year outcomes (area under the curve=0.724, P=0.014), which may be prognostic or predictive. CONCLUSIONS: Here we introduce cervical carotid tortuosity as a promising quantitative biomarker with validated, standardized characteristics. Specifically, we recommend the adoption of a curvature-based measure, total absolute curvature, for early detection or monitoring of disease progression in Loeys-Dietz syndrome.

Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis.

Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.

Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma.

PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax. PATIENTS AND METHODS: In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209). RESULTS: Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFNγ-ELISPOT assay. A statistically significant increase in IFNγ producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells. CONCLUSIONS: Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM.

Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children.

In brief: In light of the increasing age of first-time fathers, this article summarizes the current scientific knowledge base on reproductive aging in the male, including sperm quality and health impacts for the offspring. The emerging role of NAD decline in reproductive aging is highlighted. Abstract: Over the past decades, the age of first-time fathers has been steadily increasing due to socio-economic pressures. While general mechanisms of aging are subject to intensive research, male reproductive aging has remained an understudied area, and the effects of increased age on the male reproductive system are still only poorly understood, despite new insights into the potential dire consequences of advanced paternal age for the health of their progeny. There is also growing evidence that reproductive aging is linked to overall health in men, but this review mainly focuses on pathophysiological consequences of old age in men, such as low sperm count and diminished sperm genetic integrity, with an emphasis on mechanisms underlying reproductive aging. The steady decline of NAD levels observed in aging men represents one of the emerging concepts in that regard. Because it offers some mechanistic rationale explaining the effects of old age on the male reproductive system, some of the NAD-dependent functions in male reproduction are briefly outlined in this review. The overview also provides many questions that remain open about the basic science of male reproductive aging.

Accuracy of Dental Implant Placement with Dynamic Navigation-Investigation of the Influence of Two Different Optical Reference Systems: A Randomized Clinical Trial.

This randomized prospective clinical study aims to analyze the differences between the computer-assisted planned implant position and the clinically realized implant position using dynamic navigation. In the randomized prospective clinical study, 30 patients were recruited, of whom 27 could receive an implant (BLT, Straumann Institut AG, Basel, Switzerland) using a dynamic computer-assisted approach. Patients with at least six teeth in their jaws to be implanted were included in the study. Digital planning was performed using cone beam tomography imaging, and the visualization of the actual situation was carried out using an intraoral scan. Two different workflows with differently prepared reference markers were performed with 15 patients per group. The actual clinically achieved implant position was recorded with scan bodies fixed to the implants and an intraoral scan. The deviations between the planned and realized implant positions were recorded using evaluation software. The clinical examinations revealed no significant differences between procedures A and B in the mesiodistal, buccolingual and apicocoronal directions. For the mean angular deviation, group B showed a significantly more accurate value of 2.7° (95% CI 1.6-3.9°) than group A, with a value of 6.3° (95% CI 4.0-8.7°). The mean 3D deviation at the implant shoulder was 2.35 mm for workflow A (95% CI 1.92-2.78 mm) and 1.62 mm for workflow B (95% CI 1.2-2.05 mm). Workflow B also showed significantly higher accuracy in this respect. Similar values were determined at the implant apex. The clinical examination shows that sufficiently accurate implant placement is possible with the dynamic navigation system used here. The use of different workflows sometimes resulted in significantly different accuracy results. The data of the present study are comparable with the published findings of other static and dynamic navigation procedures.

Sudden Cardiac Death at Home: Potential Lives Saved With Fully Automated External Defibrillators.

Sudden cardiac death from ventricular arrhythmia kills about 350,000 people annually in the United States. This number has not improved since the widespread public availability of semi-automated external defibrillators (AEDs) and the teaching of nonbreathing cardiopulmonary resuscitation (CPR) procedures. When an out-of-hospital cardiac arrest occurs in a public space, lay witnesses do CPR in 40% of the cases and use AEDs on only 7.4% of the victims before emergency medical services (EMS) arrive. About 70% of sudden cardiac death occurs at home, where an AED is usually unavailable until EMS appears. The time from a 911 call to shock averages approximately 7 minutes in urban areas and is more than 14.5 minutes in rural environments. Because arrest onset is often not observed, arrest onset to shock times maybe even longer. Survival from cardiac arrest decreases by approximately 7 to 10% per minute of ventricular arrhythmia. A prearrest protocol is proposed for the at-home use of fully automated external defibrillators in select cardiac patients, which should reduce the arrest-to-shock interval to under 1 minute and may eliminate the need for CPR in some cases.

Exploring watercolor illusion spreading between dissected stimulus parts.

The watercolor illusion (WCI) occurs when an achromatic region is surrounded by an outer contour and inner chromatic fringe, resulting in an apparent pale tint of the same hue as the fringe. The WCI both fills in and spreads out, with the previous literature suggesting it always spreads out in the absence of an enclosing border. We examined how global stimulus configuration affects this illusion by dissecting various WCI-inducing stimuli into parts. Specifically, would color spread out of the unenclosed ends of the disconnected parts? Participants provided WCI illusion magnitude ratings and shading data indicating perceived locations of color spreading for a variety of stimulus configurations. Instead of the WCI spreading modally into the spaces between the disconnected parts, we found a global reorganization of the stimuli occurred. The dissected WCI stimuli were perceived as either amodally completed behind a white illusory surface perceptually different than the physically identical background or, as empty space between separate objects depending in part on the distance between dissected parts. This study demonstrates the WCI does not always spread outside of unenclosed borders when the global interpretation interferes with spreading. These findings highlight the importance of global configuration and perceptual organization in the WCI.

Peripheral macrophages in the development and progression of structural cerebrovascular pathologies.

The human cerebrovascular system is responsible for maintaining neural function through oxygenation, nutrient supply, filtration of toxins, and additional specialized tasks. While the cerebrovascular system has resilience imparted by elaborate redundant collateral circulation from supportive tertiary structures, it is not infallible, and is susceptible to developing structural vascular abnormalities. The causes of this class of structural cerebrovascular diseases can be broadly categorized as 1) intrinsic developmental diseases resulting from genetic or other underlying aberrations (arteriovenous malformations and cavernous malformations) or 2) extrinsic acquired diseases that cause compensatory mechanisms to drive vascular remodeling (aneurysms and arteriovenous fistulae). Cerebrovascular diseases of both types pose significant risks to patients, in some cases leading to death or disability. The drivers of such diseases are extensive, yet inflammation is intimately tied to all of their progressions. Central to this inflammatory hypothesis is the role of peripheral macrophages; targeting this critical cell type may lead to diagnostic and therapeutic advancement in this area. Here, we comprehensively review the role that peripheral macrophages play in cerebrovascular pathogenesis, provide a schema through which macrophage behavior can be understood in cerebrovascular pathologies, and describe emerging diagnostic and therapeutic avenues in this area.

Environmental management cycles for chemicals and climate change, EMC4 : A new conceptual framework contextualizing climate and chemical risk assessment and management.

The environmental management cycles for chemicals and climate change (EMC4 ) is a suggested conceptual framework for integrating climate change aspects into chemical risk management. The interaction of climate change and chemical risk brings together complex systems that are imperfectly understood by science. Making management decisions in this context is therefore difficult and often exacerbated by a lack of data. The consequences of poor decision-making can be significant for both environmental and human health. This article reflects on the ways in which existing chemicals management systems consider climate change and proposes the EMC4 conceptual framework, which is a tool for decision-makers operating at different spatial scales. Also presented are key questions raised by the tool to help the decision-maker identify chemical risks from climate change, management options, and, importantly, the different types of actors that are instrumental in managing that risk. Case studies showing decision-making at different spatial scales are also presented highlighting the conceptual framework's applicability to multiple scales. The United Nations Environment Programme's development of an intergovernmental Science Policy Panel on Chemicals and Waste has presented an opportunity to promote and generate research highlighting the impacts of chemicals and climate change interlinkages. Integr Environ Assess Manag 2024;20:433-453. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Incorporating climate change model projections into ecological risk assessments to help inform risk management and adaptation strategies: Synthesis of a SETAC Pellston Workshop®.

The impacts of global climate change are not yet well integrated with the estimates of the impacts of chemicals on the environment. This is evidenced by the lack of consideration in national or international reports that evaluate the impacts of climate change and chemicals on ecosystems and the relatively few peer-reviewed publications that have focused on this interaction. In response, a 2011 Pellston Workshop® was held on this issue and resulted in seven publications in Environmental Toxicology and Chemistry. Yet, these publications did not move the field toward climate change and chemicals as important factors together in research or policy-making. Here, we summarize the outcomes of a second Pellston Workshop® on this topic held in 2022 that included climate scientists, environmental toxicologists, chemists, and ecological risk assessors from 14 countries and various sectors. Participants were charged with assessing where climate models can be applied to evaluating potential exposure and ecological effects at geographical and temporal scales suitable for ecological risk assessment, and thereby be incorporated into adaptive risk management strategies. We highlight results from the workshop's five publications included in the special series "Incorporating Global Climate Change into Ecological Risk Assessments: Strategies, Methods and Examples." We end this summary with the overall conclusions and recommendations from participants. Integr Environ Assess Manag 2024;20:359-366. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Digital Evaluation of Vertical Ridge Augmentation with the Modified Shell Technique Using a Xenogeneic Bone Lamina: A Case Series.

Vertical ridge augmentation is a demanding and technique-sensitive surgical procedure. In the present case series, cone beam CT (CBCT) scans from the clinical routine of patients treated using a novel approach for vertical bone augmentation were assessed. All patients showed a single-tooth class 5 defect and were treated using a modification of the original shell technique. Cortical bone plates were replaced with a lamina composed of a partially demineralized porcine xenograft. CBCT scans of six consecutive patients were treated with the lamina and particulate bone from the mandibular ramus prior to a single tooth implant in the anterior maxilla were included. Pre- and postsurgical CBCT data sets were superimposed and analyzed digitally using surface matching and Boolean subtraction. The volume of the grafted area was calculated with and without the xenograft. The vertical gain of the ridge height measured in this case series varied from 7 to 11.3 mm. The mean vertical gain was 8.97 mm. The mean volume including the xenograft was 382.59 mm3 (SD 73.39) and 250.84 mm3 (SD 53.67) without the lamina. The modified shell technique used in this case series for the vertical augmentation of single-tooth class 5 defects provided sufficient bone for single implant restorations.

Active sites of atomically dispersed Pt supported on Gd-doped ceria with improved low temperature performance for CO oxidation.

"Single - atom" catalysts (SACs) have been the focus of intense research, due to debates about their reactivity and challenges toward determining and designing "single - atom" (SA) sites. To address the challenge, in this work, we designed Pt SACs supported on Gd-doped ceria (Pt/CGO), which showed improved activity for CO oxidation compared to its counterpart, Pt/ceria. The enhanced activity of Pt/CGO was associated with a new Pt SA site which appeared only in the Pt/CGO catalyst under CO pretreatment at elevated temperatures. Combined X-ray and optical spectroscopies revealed that, at this site, Pt was found to be d-electron rich and bridged with Gd-induced defects via an oxygen vacancy. As explained by density functional theory calculations, this site opened a new path via a dicarbonyl intermediate for CO oxidation with a greatly reduced energy barrier. These results provide guidance for rationally improving the catalytic properties of SA sites for oxidation reactions.

Natural history and growth rate of intracranial aneurysms in Loeys-Dietz syndrome: implications for treatment.

OBJECTIVE: Loeys-Dietz syndrome (LDS) is a heritable aortopathy associated with craniofacial abnormalities and dilatation and dissection of the aorta and its branches, as well as increased risk for intracranial aneurysms (ICAs). Given the rarity of the disease, the authors aimed to better define the natural history and role for the treatment for ICAs in these patients. METHODS: The medical records of 83 patients with LDS were retrospectively reviewed to obtain clinical and genetic history and vascular imaging of the aorta, aortic branches, and intracranial vessels. Serial radiology reports and cervical and intracranial vascular images were reviewed to determine presence, location, and size of ICAs. RESULTS: In total, 55 patients (66.3%) had at least two screening intracranial vascular examinations, and 19 (22.9%) had at least 1 ICA detected. Aneurysms were typically small (mean ± SD 3.2 ± 1.8 mm). ICAs were most often located in the cavernous carotid, followed by the ophthalmic and anterior cerebral artery vessels. The rate of ICA growth was 0.43 ± 0.53 mm/year, similar to that of the general population. Three patients underwent intervention for an ICA, with 1 procedure complicated by stroke and resulting in transient hemiparesis. Several illustrative cases detail the authors' experience with ICA growth, de novo aneurysm formation, and ICA intervention in this rare patient population. CONCLUSIONS: ICAs in patients with LDS are common, are frequently small, and have a growth rate similar to that of unruptured ICAs in the general population. More aggressive or earlier intervention for asymptomatic ICAs identified in LDS patients compared with the general population is likely unwarranted based on the authors' experience at their institution.

Low-intensity open-field blast exposure effects on neurovascular unit ultrastructure in mice.

Mild traumatic brain injury (mTBI) induced by low-intensity blast (LIB) is a serious health problem affecting military service members and veterans. Our previous reports using a single open-field LIB mouse model showed the absence of gross microscopic damage or necrosis in the brain, while transmission electron microscopy (TEM) identified ultrastructural abnormalities of myelin sheaths, mitochondria, and synapses. The neurovascular unit (NVU), an anatomical and functional system with multiple components, is vital for the regulation of cerebral blood flow and cellular interactions. In this study, we delineated ultrastructural abnormalities affecting the NVU in mice with LIB exposure quantitatively and qualitatively. Luminal constrictive irregularities were identified at 7 days post-injury (DPI) followed by dilation at 30 DPI along with degeneration of pericytes. Quantitative proteomic analysis identified significantly altered vasomotor-related proteins at 24 h post-injury. Endothelial cell, basement membrane and astrocyte end-foot swellings, as well as vacuole formations, occurred in LIB-exposed mice, indicating cellular edema. Structural abnormalities of tight junctions and astrocyte end-foot detachment from basement membranes were also noted. These ultrastructural findings demonstrate that LIB induces multiple-component NVU damage. Prevention of NVU damage may aid in identifying therapeutic targets to mitigate the effects of primary brain blast injury.

High expectations on phase locking: Better quantifying the concentration of circular data.

The degree to which unimodal circular data are concentrated around the mean direction can be quantified using the mean resultant length, a measure known under many alternative names, such as the phase locking value or the Kuramoto order parameter. For maximal concentration, achieved when all of the data take the same value, the mean resultant length attains its upper bound of one. However, for a random sample drawn from the circular uniform distribution, the expected value of the mean resultant length achieves its lower bound of zero only as the sample size tends to infinity. Moreover, as the expected value of the mean resultant length depends on the sample size, bias is induced when comparing the mean resultant lengths of samples of different sizes. In order to ameliorate this problem, here, we introduce a re-normalized version of the mean resultant length. Regardless of the sample size, the re-normalized measure has an expected value that is essentially zero for a random sample from the circular uniform distribution, takes intermediate values for partially concentrated unimodal data, and attains its upper bound of one for maximal concentration. The re-normalized measure retains the simplicity of the original mean resultant length and is, therefore, easy to implement and compute. We illustrate the relevance and effectiveness of the proposed re-normalized measure for mathematical models and electroencephalographic recordings of an epileptic seizure.