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Abstract C–C motif chemokine ligand 2 (CCL2) is a monocyte chemoattractant that promotes metastatic disease and portends a poor prognosis in many cancers. To determine the potential of anti-CCL2 inhibition as a therapy for recurrent metastatic disease in neuroblastoma, a mouse model of minimal residual disease was utilized in which residual disease was treated with anti-CCL2 monoclonal antibody with etoposide. The effect of anti-CCL2 antibody on neuroblastoma cells was determined in vitro with cell proliferation, transwell migration, and 2-dimensional chemotaxis migration assays. The in vivo efficacy of anti-CCL2 antibody and etoposide against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice. In vitro, anti-CCL2 antibody did not affect cell proliferation but significantly inhibited neuroblastoma cell and monocyte migration towards an increasing CCL2 concentration gradient. Treatment of mice with anti-CCL2 antibody combined with etoposide significantly increased survival of mice after resection of primary tumors, compared to untreated mice.

Abstract Since the turn of the century, metamaterials have gained a large amount of attention due to their potential for possessing highly nontrivial and exotic properties—such as cloaking or perfect lensing. There has been a great push to create reliable mathematical models that accurately describe the required material composition. Here, we consider a quantum graph approach to metamaterial design. An infinite square periodic quantum graph, constructed from vertices and edges, acts as a paradigm for a 2D metamaterial. Wave transport occurs along the edges with vertices acting as scatterers modelling sub-wavelength resonant elements. These resonant elements are constructed with the help of finite quantum graphs attached to each vertex of the lattice with customisable properties controlled by a unitary scattering matrix. The metamaterial properties are understood and engineered by manipulating the band diagram of the periodic structure. The engineered properties are then demonstrated in terms of the reflection and transmission behaviour of Gaussian beam solutions at an interface between two different metamaterials. We extend this treatment to N layered metamaterials using the Transfer Matrix Method. We demonstrate both positive and negative refraction and beam steering. Our proposed quantum graph modelling technique is very flexible and can be easily adjusted making it an ideal design tool for creating metamaterials with exotic band diagram properties or testing promising multi-layer set ups and wave steering effects.

Key Clinical Message CRAO is an ophthalmic and medical emergency. This case is a reminder that diagnosis and management of CRAO begins with ophthalmologists but immediately thereafter care involves emergency cardiovascular and neurological similar to cerebral stroke.

Abstract We present a numerical method for computing reflection and transmission coefficients at joints connecting composite laminated plates. The method is based on modelling joints with finite elements with boundary conditions given by the solutions of the wave finite element method for the plates in the infinite half-spaces connected to the joint. There are no restrictions on the number of plates, inter-plate angles, and material parameters of individual layers forming the composite. An L-shaped laminated plate junction is discussed in more detail. Comparisons of numerically predicted scattering coefficients with semi-analytical solutions for the selected structures are presented. The results obtained are essential for statistical energy analysis and dynamical energy analysis based calculations of the wave energy distribution in full built-up structure.

Abstract Objective The aim of this prospective pilot study is to establish an initial database to register patients diagnosed with different types of childhood glaucoma and the set-up of a national registry for childhood glaucoma (ReCG) in Germany. 28 children with different types of diagnosed childhood glaucoma, who were admitted and treated at the Childhood Glaucoma Center of the University Medical Center Mainz, Germany were included. Main outcome measures were the type of childhood glaucoma, mean intraocular pressure (IOP) and genetic data of the patients. Results The documents and questionnaires for each individual included: informed consent form of the parents, medical history form of the child, patient’s gestational history questionnaire and general anesthesia examination form. Primary congenital and secondary childhood glaucoma were revealed in 11 (39%) and 17 (61%) patients, respectively. The mean IOP measured with Perkins tonometer in all patients under general anesthesia at the time of inclusion was 17.5 ± 11.8 mmHg in the right and 17 ± 8.9 mmHg in the left eyes. In 33% of children with glaucoma mutations in the CYP1B1, FOXC1, LTBP2 and TEK genes were found. The development of specific questionnaires for childhood glaucoma provides detailed baseline data to establish a ReCG in Germany for the first time.

Abstract Frosted branch angiitis (FBA) is an uncommon form of severe retinal perivasculitis associated with systemic inflammatory/infectious diseases. In this report, we describe a case of FBA and macular edema as a result of immune recovery response in a patient newly diagnosed with HIV infection and cytomegalovirus viremia.

Abstract In this work, we present a single low-profile metamaterial that provides bandgaps of acoustic and elastic waves at the same time. This was done by ensuring impedance mismatch in two different domains, the fluid domain where the acoustic waves propagate and the solid domain where the elastic waves propagate. Through creatively designing the metamaterial, waves of certain nature and frequencies of interest were completely blocked in the solid and fluid domains simultaneously. The simulation results showed bandgaps with acoustic waves attenuation below 5 kHz and elastic waves attenuation below 10 kHz. The acoustic and elastic dispersion curves of the metamaterials were calculated for various designs with various diameters and neck lengths, and the bandgaps were calculated. These parameters can be used as means for tuning both the acoustic and elastic bandgaps. A representative design of the metamaterial was manufactured on a laser powder bed fusion system and the dynamic performance was measured at various points. The measurements were carried out using a dynamic shaker setup and the dynamic performance was in good agreement with the numerical modelling results. Such metamaterials can be used for simultaneous acoustic and elastic attenuation, as well as saving in space and material consumption, in various fields including building construction, automobile, aerospace and rocket design.

Abstract Patient survival from biventricular thrombosis is possible using mechanical support followed by cardiac transplantation.

Abstract Recent advances in additive manufacturing have enabled fabrication of phononic crystals and metamaterials which exhibit spectral gaps, or stopbands, in which the propagation of elastic waves is prohibited by Bragg scattering or local resonance effects. Due to the high level of design freedom available to additive manufacturing, the propagation properties of the elastic waves in metamaterials are tunable through design of the periodic cell. In this paper, we outline a new design approach for metamaterials incorporating internal resonators, and provide numerical and experimental evidence that the stopband exists over the irreducible Brillouin zone of the unit cell of the metamaterial (i.e. is a three-dimensional stopband). The targeted stopband covers a much lower frequency range than what can be realised through Bragg scattering alone. Metamaterials have the ability to provide (a) lower frequency stopbands than Bragg-type phononic crystals within the same design volume, and/or (b) comparable stopband frequencies with reduced unit cell dimensions. We also demonstrate that the stopband frequency range of the metamaterial can be tuned through modification of the metamaterial design. Applications for such metamaterials include aerospace and transport components, as well as precision engineering components such as vibration-suppressing platforms, supports for rotary components, machine tool mounts and metrology frames.

ObjectiveTo compare surgical success, postoperative intraocular pressure and complication rates between trabeculectomy and XEN gelstent surgery in a cohort of glaucoma patients in a typical clinical setting.MethodsA retrospective cohort study of consecutive patients with refractory open-angle glaucoma including patients who underwent either stand-alone XEN gelstent insertion with Mitomycin C or trabeculectomy with Mitomycin C between 2016 and 2018 at the University Eye Hospital Mainz, Germany. Primary outcome measure was the proportion of surgical success 1 year after surgery. Patients with an IOP ≤18mmHg, an intraocular pressure reduction of >20% and in no need of revision surgery or topical medication were considered a complete surgical success. If topical therapy was necessary, they were considered a qualified success. Multivariable logistic regression analysis was carried out for the primary outcome including gender, age, preoperative intraocular pressure and number of medication classes used preoperatively as adjustment variables.Results171 eyes of 144 patients were included, including 82 eyes of 58 patients in the XEN group and 89 eyes of 86 patients in the trabeculectomy group. The primary outcome defined as the proportion of surgical success after 1 year (mean 11.1 months ± 2.2) was similar for both groups. The complete success proportion was 65.5% (95%-CI: 55.6-75.9%) in the trabeculectomy group, and 58.5% (95%-CI: 47.6-69.4%) in the XEN group and not statistically different in our analysis model (crude OR = 0.61; 95%-CI: 0.31-1.22; adjusted OR = 0.66; 95%-CI: 0.32-1.37). The intraocular pressure reduction, as secondary outcome measure, was higher in the trabeculectomy group (10.5 mmHg) compared to the XEN group (7.2 mmHg; p = 0.003) at the 12-month follow-up.ConclusionBoth XEN gelstent implantation and trabeculectomy show similar proportions of surgical success and of complications and are therefore both recommendable for clinical routine. However, trabeculectomy seems to be more effective in lowering intraocular pressure than the XEN implantation. A prospective randomized clinical trial is necessary to evaluate differences in the long-term clinical outcome.

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive malignancy characterised by the presence of extensive desmoplasia, thought to be responsible for the poor response of patients to systemic therapies. Pancreatic stellate cells (PSCs) are key mediators in the production of this fibrotic stroma, upon activation transitioning to a myofibroblast-like, high matrix secreting phenotype. Given their importance in disease progression, characterisation of PSC activation has been extensive, however one aspect that has been overlooked is the mechano-sensing properties of the cell. Here, through the use of a physiomimetic system that recapitulates the mechanical microenvironment found within healthy and fibrotic pancreas, we demonstrate that matrix stiffness regulates activation and mechanotaxis in PSCs. We show the ability of PSCs to undergo phenotypic transition solely as a result of changes in extracellular matrix stiffness, whilst observing the ability of PSCs to durotactically respond to stiffness variations within their local environment. Our findings implicate the mechanical microenvironment as a potent contributor to PDAC progression and survival via induction of PSC activation and fibrosis, suggesting that direct mechanical reprogramming of PSCs may be a viable alternative in the treatment of this lethal disease.

The purpose of this historical review is to summarize the work of Paul of Aegina and especially his contribution to the treatment of Spine disorders and trauma. A major review of the literature was undertaken with emphasis on the treatise of Paul himself as well as those of later scholars and historians. Paul expanded the horizons of surgery of his time, using his talent to perform very complicated surgery with favorite outcomes in a variety of diseases in many fields of medicine. This review will focus especially on his use of laminectomy for spinal decompression and how his successful results led him to establish his method as a routine and safe method for the treatment of spinal stenosis. However, our knowledge of his full work is at least incomplete and, from all we know, he does not seem to mention the long term effect that such an operation has on spine stability and movement.

Abstract Introduction Congenital solitary pelvic kidney is a rare condition, and its association with an abdominal aortic aneurysm is even more unusual. To the best of our knowledge, only two such cases have been reported in the literature to date. Case presentation We report the case of a 59-year-old Caucasian man with a congenital solitary pelvic kidney, who was found to have an abdominal aortic aneurysm 83 mm in diameter. Abdominal computed tomography angiography clearly identified two renal arteries, one originating from the aortic bifurcation. and the other from the proximal portion of the right common iliac artery. At surgery, renal ischaemia was prevented by introduction of an axillofemoral shunt (consisting of two femoral cannulas and a vent tube of extracorporeal circulation) from the right axillary to the right femoral artery, and a second Argyle shunt from the right common iliac artery to the origin of the left renal artery. A 20 mm Dacron tube graft was then implanted. Our patient's postoperative renal function was normal. Conclusion The renal preservation double shunt technique used in this case seems to be effective during abdominal aortic aneurysm repair.

Abstract Introduction Osteoid osteoma is a benign tumor of the growing skeleton. It presents with pain, which is usually worse at night. The radiographic features consist of a central oval or round nidus surrounded first by a radiolucent area followed by another area of sclerotic bone. In the hand, osteoid osteoma is more commonly located in the phalanges and carpal bones. The metacarpals are the least common sites for osteoid osteoma. Case presentation We present a case of an osteoid osteoma of the left third metacarpal bone in a 36-year-old woman. The clinical and radiographic findings along with the surgical management of the lesion are presented. The pain disappeared immediately after the operation. At the 2-year follow-up, the patient was pain-free and there was no evidence of recurrence. Conclusion Physicians should be aware of the unusual presence and the atypical clinical presentation of this benign lesion in the metacarpal bones of the hand.

Abstract Introduction Popliteal artery aneurysms are the most common peripheral arterial aneurysms, and are frequently bilateral. Acute limb ischemia, rupture and compression phenomena can complicate these aneurysms when the diameter exceeds 2 cm. Case Presentation We report an 82-year-old male patient with two giant femoropopliteal aneurysms, 10.5 and 8.5 cm diameters, managed in our institution. Both aneurysms were resected and a polytetrafluoroethylene (PTFE) femoropopliteal interposition graft was placed successfully. Management and literature review are discussed. Conclusion We believe this is the first report in the medical literature of bilateral giant femoropopliteal aneurysms.