Infectious diseases are worldwide a major cause of morbidity and mortality. Fast and specific detection of pathogens such as bacteria is needed to combat these diseases. Optimal methods would be non-invasive and without extensive sample-taking/processing. Here, we developed a set of near infrared (NIR) fluorescent nanosensors and used them for remote fingerprinting of clinically important bacteria. The nanosensors are based on single-walled carbon nanotubes (SWCNTs) that fluoresce in the NIR optical tissue transparency window, which offers ultra-low background and high tissue penetration. They are chemically tailored to detect released metabolites as well as specific virulence factors (lipopolysaccharides, siderophores, DNases, proteases) and integrated into functional hydrogel arrays with 9 different sensors. These hydrogels are exposed to clinical isolates of 6 important bacteria (Staphylococcus aureus, Escherichia coli,…) and remote (≥25 cm) NIR imaging allows to identify and distinguish bacteria. Sensors are also spectrally encoded (900 nm, 1000 nm, 1250 nm) to differentiate the two major pathogens P. aeruginosa as well as S. aureus and penetrate tissue (>5 mm). This type of multiplexing with NIR fluorescent nanosensors enables remote detection and differentiation of important pathogens and the potential for smart surfaces.
Bone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the haematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists in humans remains debatable. Here, using single-cell RNA sequencing, we show a continuous landscape of highly purified human bone marrow HSCs displaying varying degrees of dormancy. We identify the orphan receptor GPRC5C, which enriches for dormant human HSCs. GPRC5C is also essential for HSC function, as demonstrated by genetic loss- and gain-of-function analyses. Through structural modelling and biochemical assays, we show that hyaluronic acid, a bone marrow extracellular matrix component, preserves dormancy through GPRC5C. We identify the hyaluronic acid–GPRC5C signalling axis controlling the state of dormancy in mouse and human HSCs.
We report the case of a 68-year-old man who developed bilateral Descemet membrane detachment (DMD) 4 weeks after successful cataract surgery and discuss the possible role of an underlying predisposition to DMD. Surgical intervention with gas injection in the anterior chamber resulted in excellent visual acuity restoration in the patient. To our knowledge, this is the first report of spontaneous bilateral DMD in the late postoperative period after cataract extraction.
Background Congenital hip dislocation (luxation) has an incidence of 0.4 – 0.7% and is regarded as a prearthrotic deformity. Thus, if not being diagnosed and treated at a very early age, extensive surgical measures are inevitable in childhood and early adulthood. Methods In the time between 01/2013 and 02/2019 we performed 28 600 hips sonographies in babies as part of general screening measures at U2 or U3. There were 71 instable, dysplastic or dislocated hips diagnosed that were treated by arthrographic, closed reduction. After a hip spica cast was applied, reposition was controlled by MRI, estimating the acetabular head index (ACI), the head coverage index (HCI) as well as the femoral headʼs sphericity or by sonography using the Graf method. Results Overall success rate was 91.6% for primary closed reduction. Patients with primarily irreducible hips were significantly older (p < 0.003) than patients with primarily successful reducible hips. Congenital dislocated hips had significantly higher ACIs (p < 0.001) and HCIs (p = 0.03) as well as significantly less well rounded femoral heads (sphericity; p < 0.001) compared to stable hips. Conclusion Early diagnosis and treatment of congenital dislocated hips by closed reduction is essential for a sufficient and regular maturation of the hips without further surgical interventions.
Chronic low-back pain (CLBP) has an increasing incidence and yields a tremendous health economic burden. There are different anatomic structures that may be responsible for CLBP, such as lumbar intervertebral discs, sacroiliac joints, nerve root dura, fascia, ligaments, and muscles. However, to a large extent, CLBP is associated with structural changes in and around the facet (zygapophyseal) joint. If conservative treatment strategies fail, symptoms and pain can effectively be reduced by denervation or rhizotomy of the medial branch of the dorsal ramus of the spinal nerve through radiofrequency ablation. In this technical description with video, we present an endoscopic technique for radiofrequency rhizotomy. This technique has the advantage of directly visualizing the facet joint as well as its surrounding structures including the medial branches.
Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field.
Cartilage tissue has a very limited ability to regenerate. Symptomatic cartilage lesions are currently treated by various cartilage repair techniques. Multiple treatment techniques have been proposed in the last 30 years. Nevertheless, no single technique is accepted as a gold standard. Minced cartilage implantation is a newer technique that has garnered increasing attention. This procedure is attractive because it is autologous, can be performed in a single surgery, and is therefore given it is cost-effective. This narrative review provides an overview of the biological potential of current cartilage regenerative repair techniques with a focus on the translational evidence of minced cartilage implantation.
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