PRELIMINARY FINDINGS OF A POTENZIATED PIEZOSURGERGICAL DEVICE AT THE RABBIT SKULL

The number of available ultrasonic osteotomes has remarkably increased. In vitro and in vivo studies have revealed differences between conventional osteotomes, such as rotating or sawing devices, and ultrasound-supported osteotomes (Piezosurgery®) regarding the micromorphology and roughness values of osteotomized bone surfaces. Objective: the present study compares the micro-morphologies and roughness values of osteotomized bone surfaces after the application of rotating and sawing devices, Piezosurgery Medical® and Piezosurgery Medical New Generation Powerful Handpiece. Methods: Fresh, standard-sized bony samples were taken from a rabbit skull using the following osteotomes: rotating and sawing devices, Piezosurgery Medical® and a Piezosurgery Medical New Generation Powerful Handpiece. The required duration of time for each osteotomy was recorded. Micromorphologies and roughness values to characterize the bone surfaces following the different osteotomy methods were described. The prepared surfaces were examined via light microscopy, environmental surface electron microscopy (ESEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy. The selective cutting of mineralized tissues while preserving adjacent soft tissue (dura mater and nervous tissue) was studied. Bone necrosis of the osteotomy sites and the vitality of the osteocytes near the sectional plane were investigated, as well as the proportion of apoptosis or cell degeneration. Results and Conclusions: The potential positive effects on bone healing and reossification associated with different devices were evaluated and the comparative analysis among the different devices used was performed, in order to determine the best osteotomes to be employed during cranio-facial surgery

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

Anwendungen maschinellen Lernens für datengetriebene Prävention auf Populationsebene

Healthcare costs are systematically rising, and current therapy-focused healthcare systems are not sustainable in the long run. While disease prevention is a viable instrument for reducing costs and suffering, it requires risk modeling to stratify populations, identify high- risk individuals and enable personalized interventions. In current clinical practice, however, systematic risk stratification is limited: on the one hand, for the vast majority of endpoints, no risk models exist. On the other hand, available models focus on predicting a single disease at a time, rendering predictor collection burdensome. At the same time, the den- sity of individual patient data is constantly increasing. Especially complex data modalities, such as -omics measurements or images, may contain systemic information on future health trajectories relevant for multiple endpoints simultaneously. However, to date, this data is inaccessible for risk modeling as no dedicated methods exist to extract clinically relevant information. This study built on recent advances in machine learning to investigate the ap- plicability of four distinct data modalities not yet leveraged for risk modeling in primary prevention. For each data modality, a neural network-based survival model was developed to extract predictive information, scrutinize performance gains over commonly collected covariates, and pinpoint potential clinical utility. Notably, the developed methodology was able to integrate polygenic risk scores for cardiovascular prevention, outperforming existing approaches and identifying benefiting subpopulations. Investigating NMR metabolomics, the developed methodology allowed the prediction of future disease onset for many common diseases at once, indicating potential applicability as a drop-in replacement for commonly collected covariates. Extending the methodology to phenome-wide risk modeling, elec- tronic health records were found to be a general source of predictive information with high systemic relevance for thousands of endpoints. Assessing retinal fundus photographs, the developed methodology identified diseases where retinal information most impacted health trajectories. In summary, the results demonstrate the capability of neural survival models to integrate complex data modalities for multi-disease risk modeling in primary prevention and illustrate the tremendous potential of machine learning models to disrupt medical practice toward data-driven prevention at population scale.Die Kosten im Gesundheitswesen steigen systematisch und derzeitige therapieorientierte Gesundheitssysteme sind nicht nachhaltig. Angesichts vieler verhinderbarer Krankheiten stellt die Prävention ein veritables Instrument zur Verringerung von Kosten und Leiden dar. Risikostratifizierung ist die grundlegende Voraussetzung für ein präventionszentri- ertes Gesundheitswesen um Personen mit hohem Risiko zu identifizieren und Maßnah- men einzuleiten. Heute ist eine systematische Risikostratifizierung jedoch nur begrenzt möglich, da für die meisten Krankheiten keine Risikomodelle existieren und sich verfüg- bare Modelle auf einzelne Krankheiten beschränken. Weil für deren Berechnung jeweils spezielle Sets an Prädiktoren zu erheben sind werden in Praxis oft nur wenige Modelle angewandt. Gleichzeitig versprechen komplexe Datenmodalitäten, wie Bilder oder -omics- Messungen, systemische Informationen über zukünftige Gesundheitsverläufe, mit poten- tieller Relevanz für viele Endpunkte gleichzeitig. Da es an dedizierten Methoden zur Ex- traktion klinisch relevanter Informationen fehlt, sind diese Daten jedoch für die Risikomod- ellierung unzugänglich, und ihr Potenzial blieb bislang unbewertet. Diese Studie nutzt ma- chinelles Lernen, um die Anwendbarkeit von vier Datenmodalitäten in der Primärpräven- tion zu untersuchen: polygene Risikoscores für die kardiovaskuläre Prävention, NMR Meta- bolomicsdaten, elektronische Gesundheitsakten und Netzhautfundusfotos. Pro Datenmodal- ität wurde ein neuronales Risikomodell entwickelt, um relevante Informationen zu extra- hieren, additive Information gegenüber üblicherweise erfassten Kovariaten zu quantifizieren und den potenziellen klinischen Nutzen der Datenmodalität zu ermitteln. Die entwickelte Me-thodik konnte polygene Risikoscores für die kardiovaskuläre Prävention integrieren. Im Falle der NMR-Metabolomik erschloss die entwickelte Methodik wertvolle Informa- tionen über den zukünftigen Ausbruch von Krankheiten. Unter Einsatz einer phänomen- weiten Risikomodellierung erwiesen sich elektronische Gesundheitsakten als Quelle prädik- tiver Information mit hoher systemischer Relevanz. Bei der Analyse von Fundusfotografien der Netzhaut wurden Krankheiten identifiziert für deren Vorhersage Netzhautinformationen genutzt werden könnten. Zusammengefasst zeigten die Ergebnisse das Potential neuronaler Risikomodelle die medizinische Praxis in Richtung einer datengesteuerten, präventionsori- entierten Medizin zu verändern

Studies on cartilage and bone disease in Mucopolysaccharidoses and Mucolipidoses

Mucopolysaccharidosis (MPS) and Mucolipidosis (ML II and III) are lysosomal storage disorders with multisystem involvement. In MPS, deficiencies of glycosaminoglycans (GAGs) degrading enzymes lead to intralysosomal GAG storage. In the MLs, defective trafficking of lysosomal enzymes to the lysosome, leads to accumulation of a combination of GAGs and several other complex molecules. GAGs are degraded by enzymes, in part extracellularly and in part intracellularly in the lysosomes after uptake through endocytosis. Intralysosomal storage in MPS and ML patients gives rise to loss of cellular function by disturbed autophagy, polyubiquitination, mitochondrial dysfunction, inflammation, apoptosis, and loss of lysosomal membrane integrity, followed by tissue damage and organ dysfunction. These events eventually determine the clinical symptoms observed in the patients. Skeletal abnormalities are common in MPS and ML patients and originate from intralysosomal storage in cells of the cartilage, bones and ligaments. A major problem of these tissues is that they are difficult to treat as vascularization is poor and cell renewal (division) is slow. The existing therapies for these diseases are unable to fully correct or prevent the abnormalities occurring in bones and cartilage. To enable development of new therapies it is crucial to understand the processes involved in abnormal cartilage and bone development as observed in MPS and ML and relate them to normal skeletal development. The aim of this thesis is to create a better understanding of the etiology and pathophysiology of cartilage and bone development in patients with mucopolysaccharidosis and mucolipidosis, the clinical course and therapeutic challenges of skeletal disease in these disorders

An Informatics Roadmap Toward a FAIR Understanding of Mitochondrial Biology and Rare Mitochondrial Disease

Mitochondrial biology is integral to our fundamental understanding of human health and many diseases. They exist in every human cell type except for red blood cells and have critical functions in metabolism, oxidative phosphorylation, oxidation-reduction, and as signaling hubs responsible for mediating protective mechanisms. Rare mitochondrial diseases (RMDs) are devastating and complex, affect multiple organ systems, and disproportionately impact young children. Despite copious existing knowledge and increased public interest, the knowledge is fragmented and difficult to access. Clinical case reports (CCRs) on RMDs contain valuable clinical insights, but they are scarce and lack the metadata necessary to facilitate their discovery among the two million CCRs on PubMed. The unstructured text data of CCRs is also ill-suited to computational approaches, limiting our ability to derive the knowledge contained within.To address these issues, I assembled all available informatics tools and resources with mitochondrial components and used them to contribute to Gene Wiki pages that enable easy access to mitochondrial knowledge for researchers, students, clinicians, and patients. Through these efforts, I made mitochondrial gene, protein, and disease knowledge widely accessible with contributions of over 4MB of content across 541 Gene Wiki pages. Concurrently, I used Gene Wiki as an educational platform to train over 50 students in the biosciences and pre-medical studies in mitochondrial biology and disease, as well as instilling effective research and writing methods in biomedicine.To impose structure on CCRs and render them FAIR (Findable, Accessible, Interoperable, Reusable), I developed and applied a standardized metadata template to RMD CCRs and codified patient symptomology with the International Statistical Classification of Disease and Related Health Problems (ICD) system. I created the open-source, cloud-based MitoCases RMD Knowledge Platform (http://mitocases.org/) to house data on 384 RMD CCRs, including 4,561 instances of 952 unique ICD codes. Supplementing CCRs with structured metadata amplifies machine-readable information content and provides a distinct improvement in searching for CCRs as compared to indexing by title and abstract. Finally, I employed these resources to conduct a thorough review of Barth syndrome and characterized the diversity of presentations, range of genetic etiologies, and treatment paradigms