[Application of a universal system of epitesis fixation in the rehabilitation of patients with maxillofacial defects]. / Proizvodstvo i primenenie universal'noi sistemy fiksatsii epitezov pri reabilitatsii patsientov s defektami litsa.

OBJECTIVE: The aim of the study was the creation of a universal epithesis fixation system that increases the reliability of its functioning in prosthetics of patients with maxillofacial defects of various genesis. MATERIAL AND METHODS: After the surgical preparation of patients, in accordance with the indications of the underlying disease, epithesis was made from rigid silicone elastomers using CAD/CAM technologies. For the production of attachments, the VT1-0 titanium alloy common in medicine was used. RESULTS: A universal epithesis fixation system was used for prosthetics of various parts of the patient's face. Depending on the clinical situation and the size of the prosthetics area, an intermediate lattice plate (mesostructure) of the appropriate size and configuration was selected. Two types of attachments were used to fix epithets: magnetic with a counterpart and non-magnetic mushroom-shaped. The universal epithesis attachment system is distinguished by the possibility of using each hole of the lattice, both for attaching it to the bone structure and for installing attachments, which makes it easy to fix the lattice to residual bone fragments and center the position of the transition elements and attachments depending on the aesthetic and functional needs of the structure in whole. CONCLUSION: The success of prosthetics largely depends on the epithesis attachment system. The proposed universal epithesis fixation system allows its use in various clinical situations and also reduces the cost of prosthetics for patients with maxillofacial defects.

Rethinking interleukin-6 blockade for treatment of COVID-19.

Interleukin-6 (IL-6) is a pleiotropic cytokine with effects in immune regulation, inflammation, and infection. The use of drugs that inhibit IL-6 biological activity has been proposed as a treatment for patients with Coronavirus Disease 2019 (COVID-19). The rationale for this approach includes commitment to the concept that inflammation is a cause of lung damage in COVID-19 and belief that IL-6 is a pro-inflammatory molecule. Observational data thought to support IL-6 inhibition include elevated circulating IL-6 levels in COVID-19 patients and association between elevated IL-6 and poor clinical outcomes. However, IL-6 has significant anti-inflammatory properties, which calls into question the rationale for employing IL-6 blockade to suppress inflammation-induced tissue injury. Also, studies suggesting a beneficial role for IL-6 in the host response to infection challenge the strategy of using IL-6 blockade to treat COVID-19. In studies of recombinant IL-6 injected into human volunteers, IL-6 levels exceeding those measured in COVID-19 patients have been observed with no pulmonary adverse events or other organ damage. These observations question the role of IL-6 as a contributing factor in COVID-19. Clinical experience with IL-6 receptor antagonists such as tocilizumab demonstrates increase in severe and opportunistic infections, raising concern about using tocilizumab and similar agents to treat COVID-19. Trials of drugs to inhibit IL-6 activity in COVID-19 are ongoing and will shed light on the role of IL-6 in COVID-19 pathogenesis. However, until more information is available, providers should exercise caution in prescribing these therapies given the potential for patient harm.

The role of citizen science in addressing grand challenges in food and agriculture research.

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term 'citizen science' has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.

Laparoscopy shows superiority over endoscopy for early detection of malignant atrophic papulosis gastrointestinal complications: a case report and review of literature.

BACKGROUND: The malignant form of atrophic papulosis (Köhlmeier-Degos disease) is a rare thrombo-occlusive vasculopathy that can affect multiple organ systems. Patients typically present with distinctive skin lesions reflective of vascular drop out. The small bowel is the most common internal organ involved, resulting in considerable morbidity and mortality attributable to ischemic microperforations. Determination of the presence of gastrointestinal lesions is critical in distinguishing systemic from the benign, cutaneous only disease and in identifying candidates for treatment. CASE PRESENTATION: We describe an 18 year old male who first presented with cutaneous atrophic papulosis but became critically ill from small bowel microperforations. He had an almost immediate and dramatic response to treatment. Prior to his presentation with acute abdomen he had upper and lower endoscopy showing areas of nonspecific patchy erythema. At laparotomy, innumerable characteristic lesions with central pearly hue and erythematous border were seen. PubMed was used for a literature search using the keywords malignant atrophic papulosis, Degos disease, endoscopy, laparoscopy and laparotomy. This search yielded 200 articles which were further analyzed for diagnostic procedures and findings. Among the 200 articles we identified only 11 cases in which endoscopy was performed. Results of endoscopy and laparotomy in our patient with malignant atrophic papulosis were compared to those in the literature. Endoscopy of the gastrointestinal tract has shown gastritis and non-specific inflammation whereas laparoscopy shows white plaques with red borders on the serosal surface of the small bowel and the peritoneum. From personal communications with other physicians worldwide, we identified three additional unpublished cases in which endoscopy revealed only minimal changes while laparoscopy showed dramatic lesions. From our experience the endoscopic findings are often subtle and nonspecific, whereas laparascopy or laparotomy will reveal pathognomic lesions on the serosal surface of the intestine. CONCLUSION: Our report contrasts the endoscopic and laparoscopic findings in malignant atrophic papulosis which suggest laparoscopy is the more powerful means of detecting gastrointestinal involvement. Imaging studies may serve as a key indicator of systemic progression. Based on our experience, laparoscopy should be performed when there is a high index of suspicion for gastrointestinal malignant atrophic papulosis, even if endoscopic examination is non-diagnostic or normal.

Automated Detection of 3D Landmarks for the Elimination of Non-Biological Variation in Geometric Morphometric Analyses.

Landmark-based morphometric analyses are used by anthropologists, developmental and evolutionary biologists to understand shape and size differences (eg. in the cranioskeleton) between groups of specimens. The standard, labor intensive approach is for researchers to manually place landmarks on 3D image datasets. As landmark recognition is subject to inaccuracies of human perception, digitization of landmark coordinates is typically repeated (often by more than one person) and the mean coordinates are used. In an attempt to improve efficiency and reproducibility between researchers, we have developed an algorithm to locate landmarks on CT mouse hemi-mandible data. The method is evaluated on 3D meshes of 28-day old mice, and results compared to landmarks manually identified by experts. Quantitative shape comparison between two inbred mouse strains demonstrate that data obtained using our algorithm also has enhanced statistical power when compared to data obtained by manual landmarking.

Rapid reperitonealization and wound healing in a preclinical model of abdominal trauma repair with a composite mesh.

PURPOSE: Peritoneal tissue healing is characterized by the simultaneous repopulation of mesothelial cells and the formation of neoperitoneum. Despite the common use of mesh products for abdominal wall repair, there are few investigations of how these materials may impact the peritoneal healing process. Here, we utilized an animal model of abdominal trauma to specifically investigate the peritoneal healing process in conjunction with a composite (poliglecaprone 25-coated polypropylene) mesh. METHODS: Abdominal wall injury was simulated in New Zealand White rabbits and peritoneal tissue was covered with composite mesh and fixed with peripheral sutures. Animals were sacrificed at regular intervals (up to 28 days) for macroscopic and microscopic evaluation. RESULTS: Mesothelial cells were consistently identified on the surface of the central areas of the implanted mesh as early as 3-5 days after implantation. From day 7 onward, the entire mesh surface was covered by neoperitoneum which matured over the remaining study intervals. Fibroblast ingrowth of the mesh was apparent by day 5 and increased over time, concurrent with fragmentation of the film on the composite mesh. CONCLUSIONS: These results suggest that composite mesh products used for abdominal wall repair do not significantly delay mesothelial repopulation. Study results also support the hypothesis that mesothelial cells involved in healing are derived, at least in part in this model, from free-floating precursor cells located within the peritoneal cavity.

Dynamics of short- and long-term association between a bacterial plant pathogen and its arthropod vector.

The dynamics of association between pathogens and vectors can strongly influence epidemiology. It has been proposed that wilt disease epidemics in cucurbit populations are sustained by persistent colonization of beetle vectors (Acalymma vittatum) by the bacterial phytopathogen Erwinia tracheiphila. We developed a qPCR method to quantify E. tracheiphila in whole beetles and frass and used it to assess pathogen acquisition and retention following variable exposure to infected plants. We found that (i) E. tracheiphila is present in frass in as little as three hours after feeding on infected plants and can be transmitted with no incubation period by vectors given brief exposure to infected plants, but also by persistently colonized vectors several weeks following exposure; (ii) duration of exposure influences rates of long-term colonization; (iii) frass infectivity (assessed via inoculation experiments) reflects bacterial levels in frass samples across time; and (iv) vectors rarely clear E. tracheiphila infections, but suffer no apparent loss of fitness. These results describe a pattern conducive to the effective maintenance of E. tracheiphila within cucurbit populations.

The ontology of craniofacial development and malformation for translational craniofacial research.

We introduce the Ontology of Craniofacial Development and Malformation (OCDM) as a mechanism for representing knowledge about craniofacial development and malformation, and for using that knowledge to facilitate integrating craniofacial data obtained via multiple techniques from multiple labs and at multiple levels of granularity. The OCDM is a project of the NIDCR-sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data. However, the OCDM should be usable for integrating any web-accessible craniofacial data, not just those data available through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA), our comprehensive ontology of canonical human adult anatomy, and includes modules to represent adult and developmental craniofacial anatomy in both human and mouse, mappings between homologous structures in human and mouse, and associated malformations. We describe these modules, as well as prototype uses of the OCDM for integrating craniofacial data. By using the terms from the OCDM to annotate data, and by combining queries over the ontology with those over annotated data, it becomes possible to create "intelligent" queries that can, for example, find gene expression data obtained from mouse structures that are precursors to homologous human structures involved in malformations such as cleft lip. We suggest that the OCDM can be useful not only for integrating craniofacial data, but also for expressing new knowledge gained from analyzing the integrated data.

A new tool for quantifying and characterizing asymmetry in bilaterally paired structures.

This paper introduces a new tool to quantify and characterize asymmetry in bilaterally paired structures. This method uses deformable registration to produce a dense vector field describing the point correspondences between two images of bilaterally paired structures. The deformation vector field properties are clustered to detect and describe regions of relevant asymmetry. Three methods are provided to analyze the asymmetries: the global asymmetry score uses cluster features to quantify overall asymmetry, the local asymmetry score quantifies asymmetry in user-defined regions of interest, and the asymmetry similarity measure quantifies pairwise similarity of individual asymmetry. The scores and image distances generated by this tool are shown to correlate highly with asymmetry ratings assigned by an expert.

MRI of weight bearing and movement.

Conventional, static magnetic resonance imaging (MRI) is able to provide a vast amount of information regarding the anatomy and pathology of the musculoskeletal system. However, patients, especially those whose pain is position dependent or elucidated by movement, may benefit from more advanced imaging techniques that allow for the acquisition of functional information. This manuscript reviews a variety of advancements in MRI techniques that are used to image the musculoskeletal system dynamically, while in motion or under load. The methodologies, advantages and drawbacks of stress MRI, cine-phase contrast MRI and real-time MRI are discussed as each has helped to advance the field by providing a scientific basis for understanding normal and pathological musculoskeletal anatomy and function. Advancements in dynamic MR imaging will certainly lead to improvements in the understanding, prevention, diagnosis and treatment of musculoskeletal disorders. It is difficult to anticipate that dynamic MRI will replace conventional MRI, however, dynamic MRI may provide additional valuable information to findings of conventional MRI.

A landmark-free framework for the detection and description of shape differences in embryos.

This paper introduces a new method to quantify and characterize shape changes during early facial development without the use of landmarks. Landmarks are traditionally used in morphometric analysis, but very few can be identified reliably across all stages of embryonic development. This method uses deformable registration to produce a dense vector field describing the point correspondences between two images. Low and mid-level features are extracted from the deformable vector field to find regions of organized differences that are biologically relevant. These methods are shown to detect regions of difference when evaluated on chick embryo images warped with small magnitude deformations in regions critical to midfacial development.

Three-dimensional head shape quantification for infants with and without deformational plagiocephaly.

OBJECTIVE: The authors developed and tested three-dimensional (3D) indices for quantifying the severity of deformational plagiocephaly (DP). DESIGN: The authors evaluated the extent to which infants with and without DP (as determined by clinic referral and two experts' ratings) could be correctly classified. PARTICIPANTS: Infants aged 4 to 11 months, including 154 with diagnosed DP and 100 infants without a history of DP or other craniofacial condition. After excluding participants with discrepant expert ratings, data from 90 infants with DP and 50 infants without DP were retained. MEASUREMENTS: Two-dimensional (2D) histograms of surface normal vector angles were extracted from 3D mesh data and used to compute the severity scores. OUTCOME MEASURES: Left posterior flattening score (LPFS), right posterior flattening score (RPFS), asymmetry score (AS), absolute asymmetry score (AAS), and an approximation of a previously described 2D measure, the oblique cranial length ratio (aOCLR). Two-dimensional histograms localized the posterior flatness for each participant. ANALYSIS: The authors fit receiver operating characteristic curves and calculated the area under the curves (AUC) to evaluate the relative accuracy of DP classification using the above measures. RESULTS: The AUC statistics were AAS = 91%, LPFS = 97%, RPFS = 91%, AS = 99%, and aOCLR = 79%. CONCLUSION: Novel 3D-based plagiocephaly posterior severity scores provided better sensitivity and specificity in the discrimination of plagiocephalic and typical head shapes than the 2D measurements provided by a close approximation of OCLR. These indices will allow for more precise quantification of the DP phenotype in future studies on the prevalence of this condition, which may lead to improved clinical care.

Anti-CD13 Abs in children with extensive chronic GVHD and their relation to soluble CD13 after allogeneic blood and marrow transplantation from a Children's Oncology Groups Study, ASCT0031.

Our group previously demonstrated a strong association between elevated plasma soluble CD13 enzyme activity and newly diagnosed extensive chronic GVHD (cGVHD) in children. As cytotoxic anti-CD13 Abs have been documented after blood and marrow transplant (BMT) in association with CMV infection and cGVHD, we hypothesized that soluble CD13 contributes to cGVHD pathogenesis by induction of CD13 reactive Abs and that anti-CD13 Abs could be additional biomarkers for newly diagnosed pediatric extensive cGVHD. Using prospectively collected plasma samples from pediatric allogeneic BMT (allo-BMT) subjects with cGVHD and controls without cGVHD enrolled in a large multi-institution Children's Oncology Group cGVHD therapeutic trial, we evaluated whether soluble CD13 correlates with induction of anti-CD13 Abs. We found that CD13 reactive Abs are present in a proportion of patients after allo-BMT, but did not seem to correlate with the presence of soluble CD13. Anti-CD13 Abs also did not meet our criteria as a diagnostic biomarker for cGVHD. These data do not confirm that induction of CD13 reactive Abs is a mechanism for cGVHD in children nor are part of the pathogenesis of cGVHD associated with elevated soluble CD13. The exact role of CD13 in cGVHD remains to be determined.

Why and how bacteria localize proteins.

Despite their small size, bacteria have a remarkably intricate internal organization. Bacteria deploy proteins and protein complexes to particular locations and do so in a dynamic manner in lockstep with the organized deployment of their chromosome. The dynamic subcellular localization of protein complexes is an integral feature of regulatory processes of bacterial cells.

Transcatheter aortic valve insertion: anaesthetic implications of emerging new technology.

Transcatheter aortic valve insertion is a new development that potentially offers a number of advantages to patients and healthcare providers. These include the avoidance of sternotomy and cardiopulmonary bypass, and much faster discharge from hospital and return to functional status. The procedure itself however is quite complex, and presents significant demands in planning and implementation to the multidisciplinary team. Anaesthetic input is essential, and patient care in the perioperative period can be challenging. Early results have shown a significant mortality and morbidity rate, but the majority of procedures to date have been carried out in elderly patients with multiple comorbidities, making comparison with surgical aortic valve replacement inappropriate. Long-term outcomes are not yet known, but randomized controlled trials should allow this procedure and its application to be properly assessed.

Dynamic chromosome organization and protein localization coordinate the regulatory circuitry that drives the bacterial cell cycle.

The bacterial cell has less internal structure and genetic complexity than cells of eukaryotic organisms, yet it is a highly organized system that uses both temporal and spatial cues to drive its cell cycle. Key insights into bacterial regulatory programs that orchestrate cell cycle progression have come from studies of Caulobacter crescentus, a bacterium that divides asymmetrically. Three global regulatory proteins cycle out of phase with one another and drive cell cycle progression by directly controlling the expression of 200 cell-cycle-regulated genes. Exploration of this system provided insights into the evolution of regulatory circuits and the plasticity of circuit structure. The temporal expression of the modular subsystems that implement the cell cycle and asymmetric cell division is also coordinated by differential DNA methylation, regulated proteolysis, and phosphorylation signaling cascades. This control system structure has parallels to eukaryotic cell cycle control architecture. Remarkably, the transcriptional circuitry is dependent on three-dimensional dynamic deployment of key regulatory and signaling proteins. In addition, dynamically localized DNA-binding proteins ensure that DNA segregation is coupled to the timing and cellular position of the cytokinetic ring. Comparison to other organisms reveals conservation of cell cycle regulatory logic, even if regulatory proteins, themselves, are not conserved.

Linking molecular affinity and cellular specificity in cadherin-mediated adhesion.

Many cell-cell adhesive events are mediated by the dimerization of cadherin proteins presented on apposing cell surfaces. Cadherin-mediated processes play a central role in the sorting of cells into separate tissues in vivo, but in vitro assays aimed at mimicking this behavior have yielded inconclusive results. In some cases, cells that express different cadherins exhibit homotypic cell sorting, forming separate cell aggregates, whereas in other cases, intermixed aggregates are formed. A third pattern is observed for mixtures of cells expressing either N- or E-cadherin, which form distinct homotypic aggregates that adhere to one another through a heterotypic interface. The molecular basis of cadherin-mediated cell patterning phenomena is poorly understood, in part because the relationship between cellular adhesive specificity and intermolecular binding free energies has not been established. To clarify this issue, we have measured the dimerization affinities of N-cadherin and E-cadherin. These proteins are similar in sequence and structure, yet are able to mediate homotypic cell patterning behavior in a variety of tissues. N-cadherin is found to form homodimers with higher affinity than does E-cadherin and, unexpectedly, the N/E-cadherin heterophilic binding affinity is intermediate in strength between the 2 homophilic affinities. We can account for observed cell aggregation behaviors by using a theoretical framework that establishes a connection between molecular affinities and cell-cell adhesive specificity. Our results illustrate how graded differences between different homophilic and heterophilic cadherin dimerizaton affinities can result in homotypic cell patterning and, more generally, show how proteins that are closely related can, nevertheless, be responsible for highly specific cellular adhesive behavior.