Axolotl mandible regeneration occurs through mechanical gap closure and a shared regenerative program with the limb.

The mandible plays an essential part in human life and, thus, defects in this structure can dramatically impair the quality of life in patients. Axolotls, unlike humans, are capable of regenerating their lower jaws; however, the underlying mechanisms and their similarities to those in limb regeneration are unknown. In this work, we used morphological, histological and transcriptomic approaches to analyze the regeneration of lateral resection defects in the axolotl mandible. We found that this structure can regenerate all missing tissues in 90 days through gap minimization, blastema formation and, finally, tissue growth, differentiation and integration. Moreover, transcriptomic comparisons of regenerating mandibles and limbs showed that they share molecular phases of regeneration, that these similarities peak during blastema stages and that mandible regeneration occurs at a slower pace. Altogether, our study demonstrates the existence of a shared regenerative program used in two different regenerating body structures with different embryonic origins in the axolotl and contributes to our understanding of the minimum requirements for a successful regeneration in vertebrates, bringing us closer to understand similar lesions in human mandibles.

Implementation of a Machine Learning Approach Evaluating Risk Factors for Complications after Single-Stage Augmentation Mastopexy.

BACKGROUND: Single-stage mastopexy augmentation is a much-debated intervention due to its complexity and the associated relatively high complication rates. This study aimed to reevaluate the risk factors for these complications using a novel approach based on artificial intelligence and to demonstrate its possible limitations. PATIENTS AND METHODS: Complete datasets of patients who underwent single-staged augmentation mastopexy during 2014-2023 at one institution by a single surgeon were collected retrospectively. These were subsequently processed and analyzed by CART, RF and XGBoost algorithms. RESULTS: A total of 342 patients were included in the study, of which 43 (12.57%) reported surgery-associated complications, whereby capsular contracture (n = 19) was the most common. BMI represented the most important variable for the development of complications (FIS = 0.44 in CART). 2.9% of the patients expressed the desire for implant change in the course, with absence of any complications. A statistically significant correlation between smoking and the desire for implant change (p < 0.001) was revealed. CONCLUSION: The importance of implementing artificial intelligence into clinical research could be underpinned by this study, as risk variables can be reclassified based on factors previously considered less or even irrelevant. Thereby we encountered limitations using ML approaches. Further studies will be needed to investigate the association between smoking, BMI and the current implant size with the desire for implant change without any complications. Moreover, we could show that the procedure can be performed safely without high risk of developing major complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A single-centre retrospective 10-year experience of the rhombic 3D condylar fracture plate for open reduction and internal fixation of condylar neck and base fractures.

Fractures of the mandibular condyle account for a significant proportion of mandibular fractures. The specific functional loads require particular specifications for the implant design used for open reduction and internal fixation of such fractures. The clinical and radiographic outcomes in patients treated using a single rhombic 3D condylar fracture plate for open reduction and internal fixation at a single institution, and who fulfilled the inclusion and exclusion criteria, are presented. The primary outcome variables were: occlusion, maximum interincisal distance and mandibular excursion at 1, 3, and 6 months postoperatively, and radiographic measurements for mandibular height and gonion angle. In total, 263 patients were included, of whom 173 (65.8%) were male and 90 (34.2%) female. The mean age was 40.4 ± 18.9 years. There was satisfactory occlusion in 98.9% of patients at the 6-month follow-up, and a significant improvement in all parameters for mandibular excursion (p < 0.001), with a reduced ramus height and an increase in the gonion angle on the fractured side. Excellent clinical and radiographic results were achieved using the rhombic-shaped implant, deeming it appropriate for the osteosynthesis of mandibular condyle fractures.

A cross-sectional study of the anatomy of the jaws of a central-European caucasian population using cone beam computer tomography as a prerequisite for designing pre-formed calcium phosphate cement scaffolds.

PURPOSE: This study aims to measure the cortical and cancellous bone thickness in the upper and lower jaws, serving as a data template for developing pre-defined calcium phosphate cement primary implant forms. These measurements are crucial for creating a biphasic scaffold. METHODS: Forty complete jaws were assessed for cortical bone shape and thickness using statistical analysis and specific software tools. Sex and age were considered, and four groups were created. RESULTS: The cumulative thickness of the cortical layer varied from region to region. In both the upper and lower jaws, the cortical layer in the molar region was significantly thicker than in the frontal region. Within the alveolar process, cortical thickness increases with distance from the alveolar crest on both sides. The oral side of the lower jaw is significantly thicker than the vestibular side. For the upper jaw, no significant differences between the oral and vestibular sides were found in this study. Additionally, it is noteworthy that men have a significantly thicker cortical layer than women. Regarding age, no significant overall differences were found. CONCLUSION: Mathematical analysis of anatomical forms using polynomial functions improves understanding of jaw anatomy. This approach facilitates the design of patient-specific scaffold structures, minimizing the need for costly and time-consuming planning and enabling more efficient implementation of optimal therapy.

Development of a test bench for biomechanical simulation-a preliminary study of mandibular forces.

Purpose: The aim of this study is to develop a test bench, which integrates different complexity levels and enables in that way a flexible and dynamic testing for mid and long term intervals as well as testing of maximum loads till implant failure of different osteosynthesis systems on the mandible. Material and Methods: For this purpose, an analysis of the state of the art regarding existing test benches was combined with interviews of clinical experts to acquire a list of requirements. Based on these requirements a design for a modular test bench was developed. During the implementation of the test stand, functional tests were continuously carried out and improvements made. Depending on the level of complexity, the test bench can be used either as an incorporated variant or as a standalone solution. In order to verify the performance and the degree of fulfilment of the requirements of these two variants of the test bench, preliminary studies were carried out for all levels of complexity. In these preliminary studies, commercially available osteosynthesis and reconstruction plates were investigated for their biomechanical behaviour and compared with data from the literature. Results: In total, fourteen test runs were performed for the different levels of complexity. Firstly, five test runs were executed to test the simplified load scenario in the incorporated variant of the test bench. High forces could be transmitted without failure of the miniplates. Secondly a quasi-static test scenario was examined using the incorporated variant with simplified load insertion. Five experiments with a number of cycles between 40,896 and 100,000 cycles were carried out. In one case the quasi-static testing resulted in a fracture of the tested reconstruction plate with a failure mode similar to the clinical observations of failure. The last four test runs were carried out using the standalone variant of the test bench simulating complex load patterns via the insertion of forces through imitated muscles. During the test runs joint forces were measured and the amplitude and vector of the resulting joint forces were calculated for both temporomandibular joints. Differences in the force transmission depending on the implant system in comparison to the zero sample could be observed. Conclusion: The presented modular test bench showed to be applicable for examination of the biomechanical behavior of the mandible. It is characterized by the adjustability of the complexity regarding the load patterns and enables the subsequent integration of further sensor technologies. Follow-up studies are necessary to further qualify and optimize the test bench.

Hepatocytes demarcated by EphB2 contribute to the progression of nonalcoholic steatohepatitis.

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor 2 (EphB2). EphB2, acting as a downstream effector of Notch signaling in hepatocytes, was sufficient to induce cell-autonomous inflammation. Knockdown of Ephb2 in hepatocytes ameliorated inflammation and fibrosis in a mouse model of NASH. Thus, EphB2-expressing hepatocytes contribute to NASH progression and may serve as a potential therapeutic target.

Socioeconomic disparities between oral cavity cancer patients in Germany.

Objective: In many countries the access to high quality medical service depends on socioeconomic factors. Therefore, these factors are associated with the treatment and prognosis of many diseases. In Germany health care is claimed to be independent from such factors due to obligatory health insurance and a well-developed medical infrastructure. Thus, socioeconomically caused health disparities should be absent. The aim of this study was to analyze the association between socioeconomic factors and the survival of oral cavity cancer in Germany. Patients and methods: In this descriptive cohort study socioeconomic status related factors as well as demographic, tumor-specific, and comorbidity factors of 500 patients treated for oral cavity cancer were obtained in the university hospital of Dresden. Pearson correlation was used to describe associations between continuous variables. Associations between categorical variables were assessed using the chi-square test. Overall and recurrence-free survival were studied using the Kaplan-Meier method. Log-rank test was carried out to test between-group differences. Cox proportional hazard models were used to estimate the risk of death and the risk of recurrence. Results: Significant differences in overall survival were found between the different educational levels and sex. Seventy-nine percent of the patients did not have a university degree or master craftsman/craftswoman. Less discrepancy was observed according to the marital status (49.4% married/engaged vs. 47.8% single, divorced, or widowed). In the multivariable analysis only sex, age at diagnosis, the Charlson score, the number of positive lymph nodes, and the nodal status were identified as independent predictors for overall survival whereas sex and the age at diagnosis were identified as independent predictors for recurrence-free survival. Conclusion: Despite the equitable health system in Germany, significant associations between overall survival of oral cavity cancer and different socioeconomic factors could be found. For elimination of these disparities, health education programs should be established in socially deprived areas. Furthermore, clinicians should keep these factors in mind when determining recall periods for dental check-ups.

Infection control measures to prevent outbreaks of COVID-19 in Quebec hemodialysis units: a cross-sectional survey.

BACKGROUND: Limited space and resources are potential obstacles to infection prevention and control (IPAC) measures in in-centre hemodialysis units. We aimed to assess IPAC measures implemented in Quebec's hemodialysis units during the spring of 2020, describe the characteristics of these units and document the cumulative infection rates during the first year of the COVID-19 pandemic. METHODS: For this cross-sectional survey, we invited leaders from 54 hemodialysis units in Quebec to report information on the physical characteristics of the unit and their perceptions of crowdedness, which IPAC measures were implemented from Mar. 1 to June 30, 2020, and adherence to and feasibility of appropriate IPAC measures. Participating units were contacted again in March 2021 to collect information on the number of COVID-19 cases in order to derive the cumulative infection rate of each unit. RESULTS: Data were obtained from 38 of the 54 units contacted (70% response rate), which provided care to 4485 patients at the time of survey completion. Fourteen units (37%) had implemented appropriate IPAC measures by 3 weeks after Mar. 1, and all 38 units had implemented them by 6 weeks after. One-third of units were perceived as crowded. General measures, masks and screening questionnaires were used in more than 80% of units, and various distancing measures in 55%-71%; reduction in dialysis frequency was rare. Data on cumulative infection rates were obtained from 27 units providing care to 4227 patients. The cumulative infection rate varied from 0% to 50% (median 11.3%, interquartile range 5.2%-20.2%) and was higher than the reported cumulative infection rate in the corresponding region in 23 (85%) of the 27 units. INTERPRETATION: Rates of COVID-19 infection among hemodialysis recipients in Quebec were elevated compared to the general population during the first year of the pandemic, and although hemodialysis units throughout the province implemented appropriate IPAC measures rapidly in the spring of 2020, many units were crowded and could not maintain physical distancing. Future hemodialysis units should be designed to minimize airborne and droplet transmission of infection.

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis.

BACKGROUND: Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose of the BNT162b2 SARS-CoV-2 vaccine is efficacious in the general population, but responses in patients receiving hemodialysis are uncertain. METHODS: We obtained serial plasma from patients receiving hemodialysis and health care worker controls before and after vaccination with 1 dose of the BNT162b2 mRNA vaccine, as well as convalescent plasma from patients receiving hemodialysis who survived COVID-19. We measured anti-receptor binding domain (RBD) immunoglobulin G (IgG) levels and stratified groups by evidence of previous SARS-CoV-2 infection. RESULTS: Our study included 154 patients receiving hemodialysis (135 without and 19 with previous SARS-CoV-2 infection), 40 controls (20 without and 20 with previous SARS-CoV-2 infection) and convalescent plasma from 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG was undetectable at 4 weeks in 75 of 131 (57%, 95% confidence interval [CI] 47% to 65%) patients receiving hemodialysis, compared with 1 of 20 (5%, 95% CI 1% to 23%) controls (p < 0.001). No patient with nondetectable levels at 4 weeks developed anti-RBD IgG by 8 weeks. Results were similar in non-immunosuppressed and younger individuals. Three patients receiving hemodialysis developed severe COVID-19 after vaccination. Among those with previous SARS-CoV-2 infection, median anti-RBD IgG levels at 8 weeks in patients receiving hemodialysis were similar to controls at 3 weeks (p = 0.3) and to convalescent plasma (p = 0.8). INTERPRETATION: A single dose of BNT162b2 vaccine failed to elicit a humoral immune response in most patients receiving hemodialysis without previous SARS-CoV-2 infection, even after prolonged observation. In those with previous SARS-CoV-2 infection, the antibody response was delayed. We advise that patients receiving hemodialysis be prioritized for a second BNT162b2 dose at the recommended 3-week interval.

Long-term Outcomes After Pulmonary Endarterectomy in 499 Patients Over a 20-Year Period.

BACKGROUND: Pulmonary endarterectomy (PEA) is a curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary hypertension (PH) after PEA is not uncommon, and its impact on long-term outcomes is poorly understood. We investigated the effects of residual PH on current long-term survival and on postoperative status. METHODS: Data of 499 consecutive patients who underwent PEA between December 1995 and December 2014 were analyzed retrospectively. Kaplan-Meier survival analysis was used to estimate the survival rates with the 95% confidence interval. RESULTS: Overall survival at 5, 10, and 15 years postoperatively was 84.8% ± 1.9%, 77.1% ± 2.7%, and 59.2% ± 5.3%, respectively. Survival after discharge at 5, 10, and 15 years was 93.9% ± 1.5%, 85.4% ± 2.6%, and 65.6% ± 5.8%, respectively. Of all, 166 patients had residual PH immediately after PEA and a poorer prognosis regarding freedom from CTEPH-related death. CTEPH-related survival at 10 years in patients with normal pulmonary artery pressure vs residual PH was 89.0% ± 2.7% vs 67.9% ± 4.7%, respectively (P < .001). There was a trend to CTEPH-related survival after discharge being affected by residual PH (P = .092). At follow-up, patients with residual PH had worse exercise tolerance (P < .001) and symptoms (P < .001) compared with those with normal pulmonary artery pressure. The probability of developing PH over time was 41.9% at 15 years. CONCLUSIONS: Survival after hospital discharge is excellent for patients undergoing PEA. Postoperative PH is associated with more symptoms and poorer functional capacity. Patients who have clinically relevant postoperative PH should be monitored closely and may be candidates for additional medical therapy.

Visual suppression at the offset of binocular rivalry.

Various paradigms can make visual stimuli disappear from awareness, but they often involve stimuli that are either relatively weak, competing with other salient inputs, and/or presented for a prolonged period of time. Here we explore a phenomenon that involves controlled perceptual disappearance of a peripheral visual stimulus without these limitations. It occurs when one eye's stimulus is abruptly removed during a binocular rivalry situation. This manipulation renders the remaining stimulus, which is still being presented to the other eye, invisible for up to several seconds. Our results suggest that this perceptual disappearance depends on a visual offset-transient that promotes dominance of the eye in which it occurs regardless of whether the eye is dominant or suppressed at the moment of the transient event. Using computational modeling, we demonstrate that standard rivalry mechanisms of interocular inhibition can indeed be complemented by a hypothesized transient-driven gating mechanism to explain the phenomenon. In essence, such a system suggests that visual awareness is dominated by the eye that receives transients and "sticks with" this eye-based dominance for some time in the absence of further transient events. We refer to this phenomenon as the "disrupted rivalry effect" and suggest that it is a potentially powerful paradigm for the study of cortical suppression mechanisms and the neural correlates of visual awareness.

OEP40, a Regulated Glucose-permeable ß-Barrel Solute Channel in the Chloroplast Outer Envelope Membrane.

Chloroplasts and mitochondria are unique endosymbiotic cellular organelles surrounded by two membranes. Essential metabolic networking between these compartments and their hosting cells requires the exchange of a large number of biochemical pathway intermediates in a directed and coordinated fashion across their inner and outer envelope membranes. Here, we describe the identification and functional characterization of a highly specific, regulated solute channel in the outer envelope of chloroplasts, named OEP40. Loss of OEP40 function in Arabidopsis thaliana results in early flowering under cold temperature. The reconstituted recombinant OEP40 protein forms a high conductance ß-barrel ion channel with subconductant states in planar lipid bilayers. The OEP40 channel is slightly cation-selective PK+/PCl- ≈ 4:1 and rectifying (i⃗/i⃖ ≅ 2) with a slope conductance of Gmax ≅ 690 picosiemens. The OEP40 channel has a restriction zone diameter of ≅1.4 nm and is permeable for glucose, glucose 1-phosphate and glucose 6-phosphate, but not for maltose. Moreover, channel properties are regulated by trehalose 6-phosphate, which cannot permeate. Altogether, our results indicate that OEP40 is a "glucose-gate" in the outer envelope membrane of chloroplasts, facilitating selective metabolite exchange between chloroplasts and the surrounding cell.

Oep23 forms an ion channel in the chloroplast outer envelope.

BACKGROUND: Metabolite, ion and protein translocation into chloroplasts occurs across two membranes, the inner and the outer envelope. Solute and metabolite channels fulfill very important functions in integrating the organelles into the metabolic network of the cell. However so far only a few have been identified. Here we describe the identification and the characterization of the outer envelope protein of 23 kDa, Oep23 from garden pea. RESULTS: Oep23 is found in the entire plant lineage from green algae to flowering plants. It is expressed in all organs and developmental states tested so far. The reconstituted recombinant protein Oep23 from pea forms a high conductance ion channel with a maximal conductance in the fully open state of 466 ± 14pS at a holding potential of +100 mV (in 250 mM KCl). The Oep23 channel is cation selective (PK+ : PCl- = 15 : 1) with a voltage dependent open probability of maximal Vmem = 0 mV. CONCLUSION: The data indicate that the Oep23 activity represents a single channel unit and does not assemble into a multiple pore complex like bacterial type porins or mitochondrial voltage dependent anion channel. Thus, Oep23 represents a new member of ion channels in the outer envelope of chloroplasts involved in solute exchange.

Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with astrocytoma treated with chemotherapy.

Ecthyma gangrenosum, presenting as embolic lesions caused by Pseudomonas aeruginosa infection, has distinct pathognomonic features and a high mortality rate in patients with bacteremia, but when recognized early is easily treated. In this case report we describe this disseminated infection in an adult patient treated with chemotherapy for an astrocytoma.

[Improved diagnostics of trauma-related disease through the application of the Life-Stressor Checklist]. / Verbesserte Diagnostik von Traumafolgestörungen durch den Einsatz der Life-Stressor Checklist.

The study examines the effectiveness of applying the Life-Stressor Checklist (LSC-R) in diagnosing trauma-related disease. The validity of a quantitative analysis of the checklist is evaluated in consideration of the dose-response effect between the number of different traumatic stressor expositions and the degree of trauma-related symptoms. The trauma checklist LSC-R was applied to 130 patients. Data on psychological symptoms was collected with the help of IES-R (PTSD symptoms) and SCL-90-R, the relevance of traumatic experiences for the genesis of disorders was assessed by expert evaluation. The dose effect replicated clearly with r=0.714 and a cut-off of ≥6 yielded a 75% agreement with the expert evaluation. The total value of the trauma checklist showed a differentiation within high-risk groups and also agreement with the severity of the traumatization. The quantitative analysis of the trauma checklist permits an effective screening for identifying trauma-related disease.

Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with astrocytoma treated with chemotherapy.

Ecthyma gangrenosum, presenting as embolic lesions caused by Pseudomonas aeruginosa infection, has distinct pathognomonic features and a high mortality rate in patients with bacteremia, but when recognized early is easily treated. In this case report we describe this disseminated infection in an adult patient treated with chemotherapy for an astrocytoma.

[Efficacy of psychological interventions on pain coping strategies in orthopedic rehabilitation of chronic low back pain]. / Wirksamkeit psychologischer Interventionen auf die Schmerzverarbeitung innerhalb einer orthopädischen Rehabilitation von chronischen Rückenschmerzen.

BACKGROUND: Within an intervention study in chronic low back pain patients treated in medical inpatient rehabilitation, a multimodal intervention program was implemented at a rehabilitation clinic (sponsored by VDR, 02508). The aim of the treatment was to reduce dysfunctional, particularly suppressive pain coping patterns. METHODS: The study was aimed as a controlled study. Data were collected before and after rehabilitation as well as follow-up. 404 persons were included. Pain-related cognitions and coping behaviour were analysed by means of Kiel Pain Inventory. RESULTS: The differences between groups were greater in the cognitive and emotional scales than in the behavior scales. Behavioral changes of the suppressive pain coping patterns in the intervention group appeared temporally delayed. DISCUSSION: The effectivity of inpatient rehabilitation can be increased and stabilised up to 0,2 difference of effect size compared to control group by a more specific intensive and interdisciplinary therapy.

Molecular properties of Kcv, a virus encoded K+ channel.

The miniature viral K+ channel Kcv represents the pore module of all K+ channels. A synthetic gene of Kcv with an elevated GC content compared to that of the wild-type gene was expressed heterologously in Pichia pastoris, and the purified protein was functionally reconstituted into liposomes. Biochemical assays reveal a remarkable cation selective stability of the channel tetramer via SDS-PAGE. Only cations, which permeate Kcv, were able to protect the oligomer against disassembly into monomers at high temperatures. Electrophysiological characterization of the single Kcv channel reveals a saturating conductance (lambda(max)) of 360 pS; the single-channel current-voltage relation was strongly rectifying with a negative slope conductance at extreme voltages. The channel was highly selective for K+ and was blocked by Ba2+ and in a side specific manner by Na+ and Cs+ also. The channel conducted Rb+, but as a consequence, the channel was shifted into a hyperactive state. We conclude that specific binding interactions of cations in the conductive pathway are an important determinant of channel stability and function.

OEP37 is a new member of the chloroplast outer membrane ion channels.

The chloroplast outer envelope protein OEP37 is a member of the growing beta-barrel protein family of the outer chloroplast membrane. The reconstituted recombinant protein OEP37 from pea forms a rectifying high conductance channel with a main conductance (lambda) of Lambda= 500 picosiemens (symmetrical 250 mm KCl). The OEP37 channel is cation-selective (P(K+)/P(K-) = 14:1) with a voltage-dependent open probability maximal at V(mem) = 0 mV. The channel pore reveals an hourglass-shaped form with different diameters for the vestibule and restriction zone. The diameters of the vestibule at the high conductance side were estimated by d = 3.0 nm and the restriction zone by d = 1.5 nm. The OEP37 channel displayed a nanomolar affinity for the precursor of the chloroplast inner membrane protein Tic32, which is imported into the chloroplast through a yet unknown pathway. Pre-proteins imported through the usual Toc pathway and synthetic control peptides, however, did not show a comparable block of the OEP37 channel. In addition to the electrophysiological characterization, we studied the gene expression of OEP37 in the model plant Arabidopsis thaliana. Here, transcripts of AtOEP37 are ubiquitously expressed throughout plant development and accumulate in early germinating seedlings as well as in late embryogenesis. The plastid intrinsic protein could be detected in isolated chloroplasts of cotyledons and rosette leaves. However, the knock-out mutant oep37-1 shows that the proper function of this single copy gene is not essential for development of the mature plant. Moreover, import of Tic32 into chloroplasts of oep37-1 was not impaired when compared with wild type. Thus, OEP37 may constitute a novel peptide-sensitive ion channel in the outer envelope of plastids with function during embryogenesis and germination.