Congenital Mandibular Hypoplasia: Patient-Specific Total Joint Replacement as a Line Extension in the Treatment of Complex Craniofacial Anomalies.

Introduction: Congenital mandibular hypoplasia (CMH) remains challenging because of the underlying combined hard and soft tissue deficiency. Treatment options include craniofacial distraction, orthognathic surgery, and autologous grafts, although the latter produces inadequate results after distraction and autologous grafting. Unsatisfactory long-term stability may cause relapse, necessitating reoperation. Material and Methods: We investigated the feasibility of using alloplastic total joint replacement (TJR) in growing and young adult CMH patients. The primary outcome was long-term reconstruction stability, without implant failure. Secondary outcomes were TMJ function and pain, and jaw movements achieved during surgery. Results: Three patients (age: 9-22 years) were treated by the same surgeon at one institution during 2018-2021. Anamnesis and clinical parameters were obtained from patient records. Preoperative 3D-scans were superimposed with postoperative 3D-scans and preoperative plans, including TJR-implant STL files, to measure jaw movement. All patients underwent prior reconstructive surgery. Mandibular movement of 16.4-20.1 mm in the sagittal direction was achieved. Post-TJR follow-up ranged from 24 to 42 months. No long-term complications occurred. At the latest follow-up, the maximal interincisal opening was between 21 and 40 mm, and all implants were functioning, without failure. Conclusion: In selected CMH cases, alloplastic TJR can deliver satisfactory medium-term results with predictable and stable outcomes, even in growing patients.

Unraveling the Chemistry of meso-Cl Tricarbocyanine Dyes in Conjugation Reactions for the Creation of Peptide Bonds.

Tricarbocyanine dyes have become popular tools in life sciences and medicine. Their near-infrared (NIR) fluorescence makes them ideal agents for imaging of thick specimens or in vivo imaging, e.g., in fluorescence-guided surgery. Among other types of cyanine dyes, meso-Cl tricarbocyanine dyes have received a surge of interest, as it emerged that their high reactivity makes them inherently tumor-targeting. As such, significant research efforts have focused on conjugating these to functional moieties. However, the syntheses generally suffer from low yields. Hereby, we report on the reaction of meso-Cl dyes with a small selection of coupling reagents to give the corresponding keto-polymethines, potentially explaining low yields and the prevalence of monofunctionalized cyanine conjugates in the current state of the art of functional near-infrared dyes. We present the synthesis and isolation of the first keto-polymethine-based conjugate and present preliminary investigation in the prostate cancer cell lines PC3 and DU145 by confocal microscopy and discuss changes to optical properties in biological media.

No Significant Bone Resorption after Open Treatment of Mandibular Condylar Head Fractures in the Medium-Term.

Open treatment of condylar head fractures (CHF) is considered controversial. In this retrospective cohort study our primary objective was therefore to assess bone resorption and remodeling as well as patients function after open treatment of CHF in a medium-term follow-up (15.1 ± 2.2 months). We included 18 patients with 25 CHF who underwent open reduction and internal fixation, between 2016 and 2021, in our analysis. The clinical data and cone-beam computed tomography (CBCT) datasets were analyzed. The condylar processes were segmented in the postoperative (T1) and follow-up (T2) CBCT scans. Volumetric and linear bone changes were the primary outcome variables, measured by using a sophisticated 3D-algorithm. The mean condylar head volume decreased non-significantly from 3022.01 ± 825.77 mm3 (T1) to 2878.8 ± 735.60 mm3 (T2; p = 0.52). Morphological alterations indicated remodeling and resorption. The pre-operative maximal interincisal opening (MIO) was 19.75 ± 3.07 mm and significantly improved to 40.47 ± 1.7 mm during follow-up (p = 0.0005). Low rates of postoperative complications were observed. Open reduction of CHF leads to good clinical outcomes and low rates of medium-term complications. This study underlines the feasibility and importance of open treatment of CHF and may help to spread its acceptance as the preferred treatment option.

Analysis of heat and cold tolerance of a freeze-tolerant soil invertebrate distributed from temperate to Arctic regions: evidence of selection for extreme cold tolerance.

Tolerance to thermal extremes is critical for the geographic distributions of ectotherm species, many of which are probably going to be modified by future climatic changes. To predict species distributions it is important to understand the potential of species to adapt to changing thermal conditions. Here, we tested whether the thermal tolerance traits of a common freeze-tolerant potworm were correlated with climatic conditions and if adaptation to extreme cold constrains the evolutionary potential for high temperature tolerance. Further, we tested if evolution of thermal tolerance traits is associated with costs in other fitness traits (body size and reproduction). Lastly, we tested if slopes of temperature-survival curves (i.e., the sensitivity distribution) are related to tolerance itself. Using 24 populations of the potworm, Enchytraeus albidus Henle (Enchytraeidae), collected from a wide range of climatic conditions, we established a common garden experiment in which we determined high and low temperature tolerance (using survival as endpoint), average reproductive output and adult body size. Heat tolerance was not related to environmental temperatures whereas lower lethal temperature was about 10 °C lower in Arctic populations than in populations from temperate regions. Reproduction was not related to environmental temperature, but was negatively correlated with cold tolerance. One explanation for the trade-off between cold tolerance and reproduction could be that the more cold-hardy populations need to channel energy to large glycogen reserves at the expense of less energy expenditure for reproduction. Adult body size was negatively related to environmental temperature. Finally, the slopes of temperature-survival curves were significantly correlated with critical temperature limits for heat and cold tolerance; i.e., slopes increased with thermal tolerance. Our results suggest that relatively heat-sensitive populations possess genetic variation, leaving room for improved heat tolerance through evolutionary processes, which may alleviate the effects of a warmer future climate in the Arctic. On the other hand, we observed relatively narrow sensitivity distributions (i.e., less variation) in the most heat tolerant populations. Taken together, our results suggest that both cold and heat tolerance can only be selected for (and improved) until a certain limit has been reached.

Referencing for intraoperative navigation: Evaluation of human bias.

Navigation-assisted surgery is the gold standard for complex reconstructive procedures of the midface and facial skeleton, and artificial and anatomical landmarks are often used for reference. The correct identification of these landmarks before surgery is crucial for the accuracy of the navigation system. This study aimed to investigate the human errors in reference point placement. This retrospective study investigated 228 reference-point positions in 51 cases where navigation was utilized. The discrepancies between the actual reference point-position and manually planned preoperative reference points were quantified using Brainlab iPlanCMF 3.0.6. The referencing methods used in these cases included dental registration splints, osteosynthesis materials, anatomical landmarks, and combinations of these methods. The average discrepancy in the actual and manually planned reference points was 0.29 ± 0.41 mm. The use of anatomical landmarks demonstrated a significantly lower deviation (p < 0.05), although the differences between the errors in reference-point placement using dental registration splints, osteosynthesis materials, or combinations of these methods were not statistically significant. The frequency of misplacement of reference points was significantly higher than expected. These errors might have been caused by human bias during manual placement of the points or intraoperative difficulties caused by extensive metal artifacts. Thus, we postulate that the surgical personnel involved in planning navigation-assisted surgery should undergo intensive training. The development of new referencing methods that are less susceptible to these causes of error might help overcome human bias.

Explorations into Peptide Nucleic Acid Contrast Agents as Emerging Scaffolds for Breakthrough Solutions in Medical Imaging and Diagnosis.

Peptide nucleic acids (PNAs, nucleic acid analogues with a peptide backbone rather than a phosphoribosyl backbone) have emerged as promising chemical agents in antigene or antisense therapeutics, as splicing modulators or in gene editing. Their main benefits, compared to DNA or RNA agents, are their biochemical stability and the lack of negative charges throughout the backbone, leading to negligible electrostatic interaction with the strand with which they are hybridizing. As a result, hybridization of PNA strands with DNA or RNA strands leads to higher binding energies and melting temperatures. A lack of natural transporters, however, necessitates the formation of PNA-containing chimeras or the formulation of nanoparticular cell delivery methods. Here, we set out to explore the progress made in using imaging agents based on PNAs in diagnostic applications and highlight selected developments and challenges.

Video recording in the delivery room: current status, implications and implementation.

Many factors determine the performance and success of delivery room management of newborn babies. Improving the quality of care in this challenging surrounding has an important impact on patient safety and on perinatal morbidity and mortality. Video recording (VR) offers the advantage to record and store work as done rather than work as recalled. It provides information about adherence to algorithms and guidelines, and technical, cognitive and behavioural skills. VR is feasible for education and training, improves team performance and results of research led to changes of international guidelines. However, studies thus far have not provided data regarding whether delivery room video recording affects long-term team performance or clinical outcomes. Privacy is a concern because data can be stored and individuals can be identified. We describe the current state of clinical practice in high- and low-resource settings, discuss ethical and medical-legal issues and give recommendations for implementation with the aim of improving the quality of care and outcome of vulnerable babies. IMPACT: VR improves performance by health caregivers providing neonatal resuscitation, teaching and research related to delivery room management, both in high as well low resource settings. VR enables information about adherence to guidelines, technical, behavioural and communication skills within the resuscitation team. VR has ethical and medical-legal implications for healthcare, especially recommendations for implementation of VR in routine clinical care in the delivery room. VR will increase the awareness that short- and long-term outcomes of babies depend on the quality of care in the delivery room.

Accuracy of Guided Surgery and Real-Time Navigation in Temporomandibular Joint Replacement Surgery.

BACKGROUND: Sophisticated guided surgery has not been implemented into total joint replacement-surgery (TJR) of the temporomandibular joint (TMJ) so far. Design and in-house manufacturing of a new advanced drilling guide with vector and length control for a typical TJR fossa component are described in this in vitro study, and its accuracy/utilization was evaluated and compared with those of intraoperative real-time navigation and already available standard drilling guides. METHODS: Skull base segmentations of five CT-datasets from different patients were used to design drilling guides with vector and length control according to virtual surgical planning (VSP) for the TJR of the TMJ. Stereolithographic models of the skull bases were printed three times for each case. Three groups were formed to compare our newly designed advanced drilling guide with a standard drilling guide and drill-tracking by real-time navigation. The deviation of screw head position, screw length and vector in the lateral skull base have been evaluated (n = 72). RESULTS: There was no difference in the screw head position between all three groups. The deviation of vector and length was significantly lower with the use of the advanced drilling guide compared with standard guide and navigation. However, no benefit in terms of accuracy on the lateral skull base by the use of real-time navigation could be observed. CONCLUSION: Since guided surgery is standard in implant dentistry and other CMF reconstructions, this new approach can be introduced into clinical practice soon, in order to increase accuracy and patient safety.

Segmented worms (Phylum Annelida): a celebration of twenty years of progress through Zootaxa and call for action on the taxonomic work that remains.

Zootaxa has been the leading journal on invertebrate systematics especially within Annelida. Our current estimates indicate annelids include approximately 20,200 valid species of polychaetes, oligochaetes, leeches, sipunculans and echiurans. We include herein the impact of Zootaxa on the description of new annelid species in the last two decades. Since 2001, there have been over 1,300 new annelid taxa published in about 630 papers. The majority of these are polychaetes (921 new species and 40 new genera) followed by oligochaetes (308 new species and 10 new genera) and leeches (21 new species). The numerous papers dealing with new polychaete species have provided us a clear picture on which polychaete families have had the most taxonomic effort and which authors and countries have been the most prolific of descriptions of new taxa. An estimated additional 10,000+ species remain to be described in the phylum, thus we urge annelid workers to continue their efforts and aid in training a new generation of taxonomists focused on this ecologically important group.

Legacy effects of temporary grassland in annual crop rotation on soil ecosystem services.

The introduction of temporary grassland into an annual crop rotation is recognized to improve soil ecosystem services, and resulting legacies can be beneficial for the following crops. In this context, the aim of the present study was to evaluate legacy effects of introducing temporary grassland into an annual crop rotation on five ecosystem services (i) soil structure maintenance (aggregate stability), (ii) water regulation (saturated hydraulic conductivity), (iii) biodiversity conservation (microbial biomass and microbial metabolic activity, as well as microorganism, enchytraeid, springtail and earthworm communities), (iv) pathogen regulation (soil suppressiveness to Verticillium dahliae), and (v) forage production and quality. Three crop rotation schemes, maintained for twelve years, were compared in four random blocks, one being an annual crop rotation without grassland (0%), another with a medium percentage of grassland (50%, corresponding to 3 years of continuous grassland in the crop rotation), and a third one with a high percentage of grassland in the crop rotation (75%, corresponding to 6 years of continuous grassland in the crop rotation). The results showed that the grassland introduction into an annual crop rotation improved, whatever the duration of the grassland, soil structure maintenance and biodiversity conservation, while it decreased pathogen regulation and did not modify water regulation. Comparing the two crop rotations that included grassland, indicated a stronger beneficial grassland legacy effect for the higher proportion of grassland concerning soil structure maintenance and biodiversity conservation. By contrast, water regulation, pathogen regulation and forage production were not affected by the legacy of the 75% grassland during the rotation. Overall, our findings demonstrated the extent to which grassland legacies are affecting the current state of soil properties and possible ecosystem services provided. To improve ecosystem services, soil management should take legacy effects into account and consider longer timeframes to apply beneficial practices.

Prenatal diagnosis of exomphalos and prediction of outcome.

The aim of this study was to detect a parameter for predicting prenatal complications or postnatal surgical options after detecting a fetal exomphalos. This was a retrospective analysis of prenatal diagnosis and outcome of fetuses with 41 cases of exomphalos in between 2007 and 2017, considering the measurement of ratios. The 41 fetuses with exomphalos were examined, 34 cases (82.9%) with karyotyping and 16 cases (39%) with an abnormal karyotype. Outcome of 39 cases showed 6 abortions (15.4%), 15 terminations (38.5%), an intrauterine fetal death (2.5%) and 17 alive babies (43.6%), which were grouped in two: small exomphalos (n = 6, 35.3%) and big exomphalos (n = 11, 64.7%). Maximal diameter of exomphalos/abdomen circumference-ratio (EDmax/AC-ratio) with a cut-off of 0.24 showed a better predictive value of postnatal primary closure. Exomphalos is correlated with abnormal karyotype. EDmax/AC-ratio gives the best prediction for postnatal primary closure of the defect.

Structural Investigations, Cellular Imaging, and Radiolabeling of Neutral, Polycationic, and Polyanionic Functional Metalloporphyrin Conjugates.

Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin-metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having "true" theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary in vitro and in vivo uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing in vitro confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using in silico approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and 111In[In] or 68Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for in vivo studies, likely because the presence of the peptide changed the behavior of the TPP-NH2 synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.

Description of Hemienchytraeus wuhanensis sp. nov. (Annelida, Clitellata, Enchytraeidae) from central China, with comments on species records of Hemienchytraeus from China.

Hemienchytraeus wuhanensis sp. nov. is described from hardwood forest soil in Wuhan, China. This moderately sized enchytraeid species of 6-9 mm body length is characterized by: (1) an oesophageal appendage with tertiary branches, (2) three pairs of secondary pharyngeal gland lobes in V, VI, VII, (3) five pairs preclitellar nephridia, from 5/6 to 9/10, (4) dorsal vessel originating in clitellar segments, (5) a girdle-shaped clitellum, (6) a relatively small male reproductive apparatus without seminal vesicle, and (7) spermathecae that extend to VI-VII. DNA barcodes of paratype specimens of the new species are provided. Previous species records of Hemienchytraeus from China are critically discussed.

CAD/CAM-based referencing aids to reduce preoperative radiation exposure for intraoperative navigation.

BACKGROUND: All intraoperative navigation systems need a referencing procedure prior to utilization, usually requiring an additional computed tomography (CT) or cone beam computed tomograph (CBCT) scan. As new techniques in the field of Computer-aided design / Computer-aided manufacturing (CAD/CAM) have evolved, it seemed favourable to develop a new referencing method not relying on additional CT or CBCT scans. METHODS: A digital maxillary dental scan was used to create a referencing splint by CAD/CAM containing four reference points. By matching scanned dental model and initial trauma-CT, the splints position and thus the reference points were digitally simulated. These splints data were imported into the navigation system in Standard Tessellation Language (STL) format. These data were also 3D printed and the resulting piece was placed on the anatomical models' teeth. The methods accuracy was then assessed in vitro. CONCLUSION: Our method for referencing of intraoperative navigation can be feasible to avoid an additional CT or CBCT prior to navigation.

Self-centering second-generation patient-specific functionalized implants for deep orbital reconstruction.

Deep and complete reconstruction of the orbital cavity has been shown to be essential for preventing enophthalmos and hypoglobus in patients with orbital defects or deformities. Additively manufactured patient-specific titanium implants provide unlimited options in design. However, implant malpositioning can still occur, even when intraoperative imaging and navigation are used. In this study, we investigated novel orbital implants containing features facilitating self-centering. Accuracy of implant placement and reconstruction of the orbital dimensions were compared retrospectively between self-centering second-generation patient-specific functionalized orbital implants (study group) and CAD-based individualized implants (control group). Design features of implants in the study group included functionalization with navigation tracks, a preventive design, and flanges - so called stabilizers - towards opposite orbital walls. Implant position was evaluated by fusion of preoperative virtual plans and the post-therapeutic imaging. Aberrances were quantified by 3D heatmap analysis. 31 patients were assigned to the study group and 50 to the control group, respectively. In the study group, most implants were designed with either one (n = 18, 58.06%) or two (n = 10, 32.26%) stabilizers. Twice (6.45%), one stabilizer had to be shortened intraoperatively. Implant fit analysis revealed a significantly more precise (p < 0.001) positioning in the study group (n = 22/31) than in the control group (n = 42/50). Self-centering second-generation patient-specific functionalized orbital implants showed significantly more accurate implant positioning, facilitating the transformation of virtual plans into patient's anatomy. The presented design provides an additional instrument for intraoperative quality control besides intraoperative imaging and navigation.

Explorations into the Effect of meso-Substituents in Tricarbocyanine Dyes: A Path to Diverse Biomolecular Probes and Materials.

Polymethine cyanine dyes have been widely recognized as promising chemical tools for a range of life science and biomedical applications, such as fluorescent staining of DNA and proteins in gel electrophoresis, fluorescence guided surgery, or as ratiometric probes for probing biochemical pathways. The photophysical properties of such dyes can be tuned through the synthetic modification of the conjugated backbone, for example, by altering aromatic cores or by varying the length of the conjugated polymethine chain. Alternative routes to shaping the absorption, emission, and photostability of dyes of this family are centered around the chemical modifications on the polymethine chain. This Minireview aims to discuss strategies for the introduction of substituents in the meso-position, their effect on the photophysical properties of these dyes and some structure-activity correlations which could help overcome common limitations in the state of the art in the synthesis.

Accurate and cost-effective mandibular biomodels: a standardized evaluation of 3D-Printing via fused layer deposition modeling on soluble support structures.

INTRODUCTION: Medical biomodels can be used for illustration of medical conditions, preoperative planning or to facilitate pre-bending of osteosynthesis material. They have been shown to be an effective and efficient method to reduce operating time, blood loss and wound stress in cranio-maxillo-facial surgery. Lately, new time and cost-efficient 3D-printing methods have been introduced into the mass-market. The aim of this study was to establish a standardized method of evaluation and consequently evaluate Fused Layer Deposition Modeling in combination with soluble support structures for fabrication of medical biomodels regarding precision and cost-effectiveness. MATERIALS & METHODS: Twenty-one biomodels of human mandibles equipped with measuring appliances were printed on a FLDM 3D-printers (Ultimaker 3 Extended) using a polyactate filament and a water-soluble Polyvinyl alcohol-based support structures. Precision of these models was compared to commercial, polyamide sintered models and the planning data. Production costs, printing times and post processing procedures were evaluated. RESULTS: Duration of printing of mandibular biomodels was between 6 h 5 min - 15 h 9 min (mean 9 h 12 min, ±2 h 25 min). The average cost of materials was €5.90 (± €1.28) per model. With an average aberrance of 0.29 mm, FLDM printing delivered a high level of accuracy. It was significantly superior to the polyamide reference models in the area of the semilunar incision, yet inferior at the coronoid process. CONCLUSION: FLDM printers are able to provide very precise biomodels at very low costs. The use of using soluble support structures reduces time, costs and equipment needed for post processing procedures close to zero.

CD44(+) tumor cells promote early angiogenesis in head and neck squamous cell carcinoma.

The role of CD44 in progression of head and neck squamous cell carcinoma (HNSCC) has been controversial. The goal of this study was to study the effects of CD44(+) tumor cells on the initial stages of tumor angiogenesis and to evaluate CD44 as a potential marker of tumor angiogenesis. The CD44 gene expression was studied using the Cancer Genome Atlas (TCGA) Head and Neck Cancer data base. Expression levels of CD44 and of microvascular density (MVD) markers were assessed by immunohistochemistry performed with tissue microarrays in a cohort of 49 HNSCC patients, 11 patients with dysplasia and 12 control oral mucosa tissues. The 4-nitroquinoline-1-oxide oral carcinogenesis mouse model was used to study CD44 expression during carcinogenesis. Gelatin sponges seeded with CD44(+), CD44(-) and unsorted cancer cells suspended in Matrigel were implanted in NOD/SCID mice into a dorsal skinfold chamber and compared to non-seeded sponges as controls. Angiogenic response was assessed by intravital microscopy. In the TCGA analysis, CD44 gene expression correlated with various pro-angiogenic genes. In human HNSCC tissues, CD44 expression was upregulated and was associated with blood vessels, although no correlation between MVD and CD44 expression was found. During oral carcinogenesis CD44 expression was upregulated. In dorsal skinfold chambers, CD44(+) cells showed a significantly higher MVD than CD44(-) or unsorted cells (p < 0.001). The results indicate that CD44(+) cells contain pro-angiogenic factors and stimulate tumor angiogenesis in HNSCC. Thus, CD44 might emerge as a potential angiogenic biomarker and a therapeutic target for anti-angiogenic therapies.