ABSTRACT
Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the N-acetylglucosamine-6-sulfate sulfatase enzyme. The deficiency of this enzyme accumulates the specific glycosaminoglycans (GAG), keratan sulfate, and chondroitin-6-sulfate mainly in bone, cartilage, and its extracellular matrix. GAG accumulation in these lesions leads to unique skeletal dysplasia in MPS IVA patients. Clinical, radiographic, and biochemical tests are needed to complete the diagnosis of MPS IVA since some clinical characteristics in MPS IVA are overlapped with other disorders. Early and accurate diagnosis is vital to optimizing patient management, which provides a better quality of life and prolonged life-time in MPS IVA patients. Currently, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available for patients with MPS IVA. However, ERT and HSCT do not have enough impact on bone and cartilage lesions in patients with MPS IVA. Penetrating the deficient enzyme into an avascular lesion remains an unmet challenge, and several innovative therapies are under development in a preclinical study. In this review article, we comprehensively describe the current diagnosis, treatment, and management for MPS IVA. We also illustrate developing future therapies focused on the improvement of skeletal dysplasia in MPS IVA.
Subject(s)
Disease Management , Mucopolysaccharidosis IV/diagnosis , Mucopolysaccharidosis IV/therapy , Bone and Bones/metabolism , Cartilage/metabolism , Chondroitin Sulfates/metabolism , Early Diagnosis , Enzyme Replacement Therapy/methods , Genetic Therapy/methods , Glycosaminoglycans/metabolism , Hematopoietic Stem Cell Transplantation/methods , Humans , Keratan Sulfate/metabolism , Lysosomes/metabolism , Mucopolysaccharidosis III/genetics , Mucopolysaccharidosis III/metabolism , Mucopolysaccharidosis IV/genetics , Mucopolysaccharidosis IV/pathology , Nanomedicine , Osteochondrodysplasias , Quality of LifeABSTRACT
In this work, we design, by means of a non-neutral plasma method, a linear trapping model for large ion clouds, which will become the core of an atomic clock. We first obtain the geometry and electromagnetic characteristics of the ion trap. We then perform a systematic analysis describing the main parameters of the ion cloud such as size, secular frequency, and ion number per unit length of temperature. The most appropriate operation point of the ion trap in a set of these specific parameters is evaluated, and a thorough discussion is performed about how minor perturbations introduced in these parameters affect, in a nonlinear response, the performance of the trapping system in sensibility, heating, and radiofrequency potential.
ABSTRACT
In this Letter we employ the general coupled-mode equations of the nonlinear directional coupler and demonstrate that the switching characteristics of prototypical nonlinear racetrack-resonator structures may differ considerably from those obtained when the standard, generally incorrect, coupled-mode equations are used.
