Vitality of autologous retromolar bone grafts for alveolar ridge augmentation after a 3-months healing period: A prospective histomorphometrical analysis.

OBJECTIVES: The incorporation of retromolar bone grafts used for alveolar ridge augmentation is not well understood. This prospective observational study aims to supply histomorphometrical data from bone graft biopsies taken at the time of retrieval and after a 3-month healing period using patient-matched biopsies. MATERIALS AND METHODS: In 17 patients, trephine biopsies of the graft were acquired at the time of graft retrieval and after a 3-month healing period. The biopsies were compared histomorphometrically regarding the number of osteocytes, appearance of osteocyte lacunae, quantity, surface area, and activity of the Haversian canals. RESULTS: All grafts appeared clinically stable after screw removal and 17 implants were placed. Histomorphometric analysis revealed no significant difference in the number of osteocytes (p = .413), osteocyte lacunae (p = .611), the ratio of filled/empty osteocyte lacunae (p = .467) and active Haversian canals (p = .495) between the biopsies retrieved after a 3-months healing period with those at the time of grafting. The only significant difference was noted in the mean surface area of the Haversian canals (p = .002). Specifically, the grafts post 3-month healing showed a significantly larger mean area (0.069 mm2) compared to the time of grafting (0.029 mm2). CONCLUSION: This study demonstrates, compared to other data, a high rate of vital structures in retromolar bone block grafts after 3 months of healing, exhibiting the same histological features in comparison to the biopsies from the native alveolar ridge. Standard histomorphometrical parameters, e.g., the amount of filled or empty osteocyte lacunae for the description of the vitality of the graft need to be reappraised.

Reconstruction of dental roots for implant planning purposes: a retrospective computational and radiographic assessment of single-implant cases.

PURPOSE: The aim of the study was to assess the deviation between clinical implant axes (CIA) determined by a surgeon during preoperative planning and reconstructed tooth axes (RTA) of missing teeth which were automatically computed by a previously introduced anatomical SSM. METHODS: For this purpose all available planning datasets of single-implant cases of our clinic, which were planned with coDiagnostix Version 9.9 between 2018 and 2021, were collected for retrospective investigation. Informed consent was obtained. First, the intraoral scans of implant patients were annotated and subsequently analyzed using the SSM. The RTA, computed by the SSM, was then projected into the preoperative planning dataset. The amount and direction of spatial deviation between RTA and CIA were then measured. RESULTS: Thirty-five patients were implemented. The mean distance between the occlusal entry point of anterior and posterior implants and the RTA was 0.99 mm ± 0.78 mm and 1.19 mm ± 0.55, respectively. The mean angular deviation between the CIA of anterior and posterior implants and the RTA was 12.4° ± 3.85° and 5.27° ± 2.97° respectively. The deviations in anterior implant cases were systematic and could be corrected by computing a modified RTA (mRTA) with decreased deviations (0.99 mm ± 0.84 and 4.62° ± 1.95°). The safety distances of implants set along the (m)RTA to neighboring teeth were maintained in 30 of 35 cases. CONCLUSION: The RTA estimated by the SSM revealed to be a viable implant axis for most of the posterior implant cases. As there are natural differences between the anatomical tooth axis and a desirable implant axis, modifications were necessary to correct the deviations which occurred in anterior implant cases. However, the presented approach is not applicable for clinical use and always requires manual optimization by the planning surgeon.

Case report: Acute kidney injury as the initial manifestation of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder often diagnosed after incidental finding of leukocytosis. Renal involvement is usually clinically silent. Symptomatic renal impairment due to CLL/small lymphocytic lymphoma (SLL) cell infiltration in the kidney tissue is uncommon, and acute kidney injury (AKI) as a presenting feature is rare. In this case report, we describe the case of a patient with AKI caused by CLL/SLL infiltration as a presenting feature. Our report highlights the possibility of kidney injury as the first evident symptom of CLL/SLL. Kidney biopsy is the mainstay in these cases in order to establish a diagnosis. Treatment with zanubrutinib resulted in improved kidney function.

Comparison of the 3D-microstructure of human alveolar and fibula bone in microvascular autologous bone transplantation: a synchrotron radiation µ-CT study.

Introduction: Autologous bone transplantation is successfully used in reconstructive surgery of large/critical-sized bone defects, whereby the microvascular free fibula flap is still regarded as the gold standard for the reconstruction of such defects in the head and neck region. Here, we report the morphological and lacunar properties of patient-paired bone samples from eight patients from the jaw (AB; recipient site) and the fibula (FB; donor site) on the micron length-scale using Synchrotron µ-CT. Insights into differences and similarities between these bone structures could offer a better understanding of the underlying mechanism for successful surgical outcomes and might clear the path for optimized, nature-inspired bone scaffold designs. Methods: Spatial vessel-pore arrangements, bone morphology, fluid-simulation derived permeability tensor, osteocyte lacunar density, and lacunar morphology are compared. Results: The orientation of the vessel system indicates a homogenous vessel orientation for AB and FB. The average mineral distance (50%) to the closest vessel boundary is higher in AB than in FB (the mean is 96 µm for AB vs. 76 µm for FB; p = 0.021). Average osteocyte lacunar density is found to be higher in AB than in FB (mean 22,874 mm3 vs. 19,376 mm3 for FB; p = 0.038), which might compensate for the high distance from the mineral to the nearest vessel. No significant differences in lacunar volume are found between paired AB and FB. Discussion: A comparable vessel network and similar distribution of vessel porosity between AB and FB may allow the FB graft to exhibit a high regeneration potential when connected to AB, and this might correlate with a high osteoinductive and osteoconductive potential of FB when connected to AB. Since widely used and potent synthetic bone grafts exist, new insight into the bone structure of well-established autologous bone grafts, such as the free fibula flap, could help to improve the performance of such materials and therefore the design of 3D scaffolds.

Basic Principles of RNA Interference: Nucleic Acid Types and In Vitro Intracellular Delivery Methods.

Since its discovery in 1989, RNA interference (RNAi) has become a widely used tool for the in vitro downregulation of specific gene expression in molecular biological research. This basically involves a complementary RNA that binds a target sequence to affect its transcription or translation process. Currently, various small RNAs, such as small interfering RNA (siRNA), micro RNA (miRNA), small hairpin RNA (shRNA), and PIWI interacting RNA (piRNA), are available for application on in vitro cell culture, to regulate the cells' gene expression by mimicking the endogenous RNAi-machinery. In addition, several biochemical, physical, and viral methods have been established to deliver these RNAs into the cell or nucleus. Since each RNA and each delivery method entail different off-target effects, limitations, and compatibilities, it is crucial to understand their basic mode of action. This review is intended to provide an overview of different nucleic acids and delivery methods for planning, interpreting, and troubleshooting of RNAi experiments.

Spatially Tunable Spin Interactions in Neutral Atom Arrays.

Analog quantum simulations with Rydberg atoms in optical tweezers routinely address strongly correlated many-body problems due to the hardware-efficient implementation of the Hamiltonian. Yet, their generality is limited, and flexible Hamiltonian-design techniques are needed to widen the scope of these simulators. Here we report on the realization of spatially tunable interactions for XYZ models implemented by two-color near-resonant coupling to Rydberg pair states. Our results demonstrate the unique opportunities of Rydberg dressing for Hamiltonian design in analog quantum simulators.

Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity.

Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomization (MR) was used to identify plasma proteins associating with CMR traits as well as with any of the following cardiac outcomes: HF, non-ischemic cardiomyopathy, dilated cardiomyopathy (DCM), atrial fibrillation, or coronary heart disease. In total, 33 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7. In addition, 13 of the 25 druggable proteins (52%; 95% confidence interval, 0.31 to 0.72) could be mapped to compounds with known oncological indications or side effects. These findings provide leads to facilitate drug development for cardiac disease and suggest that cardiotoxicities of several cancer treatments might represent mechanism-based adverse effects.

Dental MRI-only a future vision or standard of care? A literature review on current indications and applications of MRI in dentistry.

MRI is increasingly used as a diagnostic tool for visualising the dentoalveolar complex. A comprehensive review of the current indications and applications of MRI in the dental specialities of orthodontics (I), endodontics (II), prosthodontics (III), periodontics (IV), and oral surgery (V), pediatric dentistry (VI), operative dentistry is still missing and is therefore provided by the present work.The current literature on dental MRI shows that it is used for cephalometry in orthodontics and dentofacial orthopaedics, detection of dental pulp inflammation, characterisation of periapical and marginal periodontal pathologies of teeth, caries detection, and identification of the inferior alveolar nerve, impacted teeth and dentofacial anatomy for dental implant planning, respectively. Specific protocols regarding the miniature anatomy of the dentofacial complex, the presence of hard tissues, and foreign body restorations are used along with dedicated coils for the improved image quality of the facial skull.Dental MRI poses a clinically useful radiation-free imaging tool for visualising the dentoalveolar complex across dental specialities when respecting the indications and limitations.

Bilateral non-contiguous necrotizing fasciitis of the lower extremities.

Necrotizing fasciitis (NF) is an uncommon soft tissue infection. Multifocal-extremity NF is a rarity with high mortality rates. Herein we report a case of bilateral non-contiguous NF of the lower extremities due to Escherichia coli with a fatal outcome, stressing the necessity of rapid and aggressive intervention in suspected cases.

Feasibility of Implant Strain Measurement for Assessing Mandible Bone Regeneration.

Nonunion is one of the most dreaded complications after operative treatment of mandible fractures or after mandible reconstruction using vascularized and non-vascularized bone grafts. Often diagnosis is made at advanced stage of disease when pain or complications occur. Devices that monitor fracture healing and bone regeneration continuously are therefore urgently needed in the craniomaxillofacial area. One promising approach is the strain measurement of plates. An advanced prototype of an implantable strain measurement device was tested after fixation to a locking mandible reconstruction plate in multiple compression experiments to investigate the potential functionality of strain measurement in the mandibular region. Compression experiments show that strain measurement devices work well under experimental conditions in the mandibular angle and detect plate deformation in a reliable way. For monitoring in the mandibular body, the device used in its current configuration was not suitable. Implant strain measurement of reconstruction plates is a promising methodical approach for permanent monitoring of bone regeneration and fracture healing in the mandible. The method helps to avoid or detect complications at an early point in time after operative treatment.

Impurities in commercial titanium dental implants - A mass and optical emission spectrometry elemental analysis.

OBJECTIVE: Titanium (Ti) is considered bioinert and is still regarded as the "gold standard" material for dental implants. However, even 'commercial pure' Ti will contain minor fractions of elemental impurities. Evidence demonstrating the release of Ti ions and particles from 'passive' implant surfaces is increasing and has been attributed to biocorrosion processes which may provoke immunological reactions. However, Ti observed in peri-implant tissues has been shown to be co-located with elements considered impurities in biomedical alloys. Accordingly, this study aimed to quantify the composition of impurities in commercial Ti dental implants. METHODS: Fifteen commercial titanium dental implant systems were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). RESULTS: The elemental composition of implants manufactured from commercially pure grades of Ti, Ti-6Al-4V, and the TiZr alloy (Roxolid) conformed to the respective ISO/ASTM standards or manufacturers´ data (TiZr/Roxolid). However, all implants investigated included exogenous metal contaminants including Ni, Cr, Sb, and Nb to a variable extent. Other contaminants detected in a fraction of implants included As and the radionuclides U-238 and Th-232. SIGNIFICANCE: Although all Ti implant studies conformed with their standard compositions, potentially allergenic, noxious metals and even radionuclides were detected. Since there are differences in the degree of contamination between the implant systems, a certain impurity fraction seems technically avoidable. The clinical relevance of these findings must be further investigated, and an adaptation of industry standards should be discussed.

Comparison of the 3D-Microstructure Between Alveolar and Iliac Bone for Enhanced Bioinspired Bone Graft Substitutes.

In oral- and maxillofacial bone augmentation surgery, non-vascularized grafts from the iliac crest demonstrate better clinical performance than alveolar bone grafts. The underlying mechanisms are not fully understood but are essential for the enhancement of bone regeneration scaffolds. Synchrotron Radiation µ-CT at a pixel size of 2.3 µm was used to characterize the gross morphology and the vascular and osteocyte lacuna porosity of patient-matched iliac crest/alveolar bone samples. The results suggest a difference in the spatial distribution of the vascular pore system. Fluid simulations reveal the permeability tensor to be more homogeneous in the iliac crest, indicating a more unidirectional fluid flow in alveolar bone. The average distance between bone mineral and the closest vessel pore boundary was found to be higher in alveolar bone. At the same time, osteocyte lacunae density is higher in alveolar bone, potentially compensating for the longer average distance between the bone mineral and vessel pores. The present study comprehensively quantified and compared the 3D microarchitecture of intraindividual human alveolar and iliac bone. The identified difference in pore network architecture may allow a bone graft from the iliac crest to exhibit higher regeneration potential due to an increased capacity to connect with the surrounding pore network of the residual bone. The results may contribute to understanding the difference in clinical performance when used as bone grafts and are essential for optimization of future scaffold materials.

Realizing the symmetry-protected Haldane phase in Fermi-Hubbard ladders.

Topology in quantum many-body systems has profoundly changed our understanding of quantum phases of matter. The model that has played an instrumental role in elucidating these effects is the antiferromagnetic spin-1 Haldane chain1,2. Its ground state is a disordered state, with symmetry-protected fourfold-degenerate edge states due to fractional spin excitations. In the bulk, it is characterized by vanishing two-point spin correlations, gapped excitations and a characteristic non-local order parameter3,4. More recently it has been understood that the Haldane chain forms a specific example of a more general classification scheme of symmetry-protected topological phases of matter, which is based on ideas connected to quantum information and entanglement5-7. Here, we realize a finite-temperature version of such a topological Haldane phase with Fermi-Hubbard ladders in an ultracold-atom quantum simulator. We directly reveal both edge and bulk properties of the system through the use of single-site and particle-resolved measurements, as well as non-local correlation functions. Continuously changing the Hubbard interaction strength of the system enables us to investigate the robustness of the phase to charge (density) fluctuations far from the regime of the Heisenberg model, using a novel correlator.

Realizing Distance-Selective Interactions in a Rydberg-Dressed Atom Array.

Measurement-based quantum computing relies on the rapid creation of large-scale entanglement in a register of stable qubits. Atomic arrays are well suited to store quantum information, and entanglement can be created using highly-excited Rydberg states. Typically, isolating pairs during gate operation is difficult because Rydberg interactions feature long tails at large distances. Here, we engineer distance-selective interactions that are strongly peaked in distance through off-resonant laser coupling of molecular potentials between Rydberg atom pairs. Employing quantum gas microscopy, we verify the dressed interactions by observing correlated phase evolution using many-body Ramsey interferometry. We identify atom loss and coupling to continuum modes as a limitation of our present scheme and outline paths to mitigate these effects, paving the way towards the creation of large-scale entanglement.

Aspirin, heparin and ischemia time in microvascular free flap surgery - their influence and an optimal anticoagulation protocol.

BACKGROUND: Microvascular surgery has become a standardized technique for reconstruction of large tissue defects in Head and Neck Reconstructive Surgery. However, the main dreaded complications are thrombosis of blood vessels or major bleeding after surgery. Several different anticoagulation protocols have been established in the last decades to overcome these problems with varying degrees of success. METHODS: Over a period of six years, a standardized anticoagulation protocol including acetylsalicylic acid (ASA) and unfractionated heparin (UFH) for direct intraoperative and postoperative administration was established, optimized and compared to a previously used non-standardized protocol. A total of 178 flap surgeries were included in the development and optimization process of the protocol. RESULTS: ASA significantly increased the risk of complications when used for longer than 72 h (OR = 2.52; p = 0.002; 95% CI 1.39-4.59). Administration of UFH reduced flap loss (bolus: OR 0.68; p = 0.47; 95% CI 0.24-1.93; continuous UFH administration: OR = 0.61; p = 0.33; 95% CI 0.22-1.66), however doses greater than 500 IU/ h of UFH as continuous infusion increased the risk of complications. Reduction in ischemia time had no effect on the occurrence of complications. CONCLUSION: Anticoagulation regimes in microvascular surgery can influence the postoperative complication rate. The optimal protocol should consist of a combination of ASA and UFH for the intraoperative and direct postoperative phase. Prolonged administration of ASA as well as doses >500 IU/ h of UFH are to be avoided due to the increased complication rate.

Radiation exposure to the kidney with interstitial iridium-192 high-dose-rate brachytherapy: Extent and rare morphologic changes of radiation nephropathy.

Purpose: We sought to investigate functional parameters and morphologic changes of the renal parenchyma after treatment with image-guided brachytherapy using single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) of primary kidney lesions, and primary and secondary lesions of the liver, lymph node, and adrenal gland close to renal structures. Material and methods: Patients ineligible for surgery were included. We prospectively investigated renal function loss within one year via renal scintigraphy and laboratory parameters (KDOQI stage). Radiation exposure to the kidney was measured by volume receiving 5 Gy (V5). We observed morphologic changes on CT or MRI, with follow-up every three months. Results: In total, 35 patients were included (21 males, 14 females). Eight patients were treated for extra-renal malignancies. The mean V5 of the ipsilateral kidney was 70.0 ±42.4 ml equaling to 44.9% parenchymal volume. After renal treatment, V5 renal volume was 77.8 ±42.2 ml (48.7%) compared with 44.0 ±33.0 ml (32.0%) after extra-renal treatment. No significant reduction in KDOQI stage after 12 months of follow-up were found. Three patients developed morphologic changes in the renal parenchyma, with only one showing a decrease in renal function after 12 months. Conclusions: CT-guided HDR-BT is a viable treatment modality for local ablative treatment of renal and adjacent masses, with no significant reduction of the KDOQI stage as a predictor for complications of chronic kidney disease. However, larger cohorts need to be analyzed to identify vulnerable patients, as in rare cases, plain dosimetry seems insufficient to predict renal function loss after HDR-BT.

Microscopic evolution of doped Mott insulators from polaronic metal to Fermi liquid.

The competition between antiferromagnetism and hole motion in two-dimensional Mott insulators lies at the heart of a doping-dependent transition from an anomalous metal to a conventional Fermi liquid. We observe such a crossover in Fermi-Hubbard systems on a cold-atom quantum simulator and reveal the transformation of multipoint correlations between spins and holes upon increasing doping at temperatures around the superexchange energy. Conventional observables, such as spin susceptibility, are furthermore computed from the microscopic snapshots of the system. Starting from a magnetic polaron regime, we find the system evolves into a Fermi liquid featuring incommensurate magnetic fluctuations and fundamentally altered correlations. The crossover is completed for hole dopings around 30%. Our work benchmarks theoretical approaches and discusses possible connections to lower-temperature phenomena.

Accelerated discovery of functional genomic variation in pigs.

The genotype-phenotype link is a major research topic in the life sciences but remains highly complex to disentangle. Part of the complexity arises from the number of genes contributing to the observed phenotype. Despite the vast increase of molecular data, pinpointing the causal variant underlying a phenotype of interest is still challenging. In this study, we present an approach to map causal variation and molecular pathways underlying important phenotypes in pigs. We prioritize variation by utilizing and integrating predicted variant impact scores (pCADD), functional genomic information, and associated phenotypes in other mammalian species. We demonstrate the efficacy of our approach by reporting known and novel causal variants, of which many affect non-coding sequences. Our approach allows the disentangling of the biology behind important phenotypes by accelerating the discovery of novel causal variants and molecular mechanisms affecting important phenotypes in pigs. This information on molecular mechanisms could be applicable in other mammalian species, including humans.