Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management.

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

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Markers of cognitive function in individuals with metabolic disease: Morquio Syndrome and Tyrosinemia Type III

We characterized cognitive function in two metabolic diseases. MPS–IVa (mucopolysaccharidosis IVa, Morquio) and tyrosinemia type III individuals were assessed using tasks of attention, language and oculomotor function. MPS–IVa individuals were slower in visual search, but the display size effects were normal, and slowing was not due to long reaction times (ruling out slow item processing or distraction). Maintaining gaze in an oculomotor task was difficult. Results implicated sustained attention and task initiation or response processing. Shifting attention, accumulating evidence and selecting targets were unaffected. Visual search was also slowed in tyrosinemia type III, and patterns in visual search and fixation tasks pointed to sustained attention impairments, although there were differences from MPS–IVa. Language was impaired in tyrosinemia type III but not MPS–IVa. Metabolic diseases produced selective cognitive effects. Our results, incorporating new methods for developmental data and model selection, illustrate how cognitive data can contribute to understanding function in biochemical brain systems

Multi-objective optimal design of inerter-based vibration absorbers for earthquake protection of multi-storey building structures

In recent years different inerter - based vibration absorbers (IVAs) emerged for the earthquake protection of building structures coupling viscous and tuned - mass dampers with an inerter device . In the three most popular IVAs the inerter is functioning either as a motion amplifier [tuned - viscous - mass - damper (TVMD) configuration], mass amplifier [tuned - mass - damper - inerter (T MDI) configuration], or mass substitute [tuned - inerter - damper (TID) configuration]. Previous work has shown that through proper tuning , IVAs achieve enhanced earthquake - induced vibration suppression and/or weight reduction compared to conventional dampers/absorbers , but at the expense of increased control forces exerted from the IVA to the host building structure . These potentially large forces are typically not accounted for by current IVA tuning approaches. In this regard, a multi-objective IVA design approach is herein developed to identify the compromise between the competing objectives of (i) suppressing earthquake-induced vibrations in buildings, and (ii) avoiding development of excessive IVA (control) forces, while, simultaneously, assessing the appropriateness of different modeling assumptions for practical design of IVAs for earthquake engineering applications . The potential of the approach to pinpoint Pareto optimal IVA designs against the above objectives is illustrated for different IVA placements along the height of a benchmark 9-storey steel frame structure. Objective (i) is quantified according to current performanc e-based seismic design trends using first-passage reliability criteria associated with the probability of exceeding pre-specified thresholds of storey drifts and/or floor accelerations being the engineering demand parameters (EDPs) of interest . A variant, simpler, formulation is also considered using as performance quantification the sum of EDPs variances in accordance to traditional tuning methods for dynamic vibration absorbers. Objective (ii) is quantified through the variance of the IVA force. It is found that reduction of IVA control force of up to 3 times can be achieved with insignificant deterioration of building performance com pared to the extreme Pareto optimal IVA design targeting maximum vibration suppression , while TID and TMDI a chieve practically the same building performance and significantly outperform the TVMD. Moreover, it is shown that the simpler variant formulation may provide significantly suboptimal reliability performance . Lastly, it is verified that the efficacy of optimal IVA designs for stationary conditions is maintained for non-stationary stochastic excitation model capturing typical evolutionary features of earthquake excitations

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance.

IntroductionMucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA.MethodsTwenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.ResultsA total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).ConclusionThis manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps

IVA the robot: Design guidelines and lessons learned from the first space station laboratory manipulation system

The first interactive Space Station Freedom (SSF) lab robot exhibit was installed at the Space and Rocket Center in Huntsville, AL, and has been running daily since. IntraVehicular Activity (IVA) the robot is mounted in a full scale U.S. Lab (USL) mockup to educate the public on possible automation and robotic applications aboard the SSF. Responding to audio and video instructions at the Command Console, exhibit patrons may prompt IVA to perform a housekeeping task or give a speaking tour of the module. Other exemplary space station tasks are simulated and the public can even challenge IVA to a game of tic tac toe. In anticipation of such a system being built for the Space Station, a discussion is provided of the approach taken, along with suggestions for applicability to the Space Station Environment

HUBUNGAN TINGKAT PENGETAHUAN IBU TENTANG IVA DENGAN PERILAKU IBU TENTANG IVA DI RT 02 / RW 01 KELURAHAN DARMO SURABAYA

Salah satu program skrining kanker serviks adalah pemeriksaan IVA. Upaya memerangi kanker servik di masyarakat banyak menemui kendala, salah satunya adalah kurang tanggapnya para WUS untuk memeriksakan dirinya dilayanan kesehatan. Tujuan penelitian ini adalah untuk mengetahui hubungan antara tingkat pengetahuan ibu tentang IVA dengan perilaku ibu melakukan IVA. Rancang bangun penelitian ini menggunakan metode analitik observasional dengan pendekatan cross sectional. Populasi dalam penelitian ini adalah semua wanita yang sudah menikah sebesar 63 responden dan besar sampelnya adalah 55 responden yang diambil dengan cara simple random sampling. Variabel independen pengetahuan ibu tentang IVA dan dependen perilaku ibu melakukan IVA. Data diperoleh dengan menggunakan kuesioner. Kemudian dianalisis secara analitik dengan menggunakan Uji Mann Whitney dengan tingkat kemaknaan α=0,05. Hasil penelitian menunjukkan bahwa hampir setengahnya (47%) ibu memiliki pengetahuan kurang dan hampir seluruhnya (90,1%) tidak rutin melakukan kunjungan IVA. Hasil Uji Mann Whitney menunjukkan ρ = 0,001 < α = 0,05 , maka H0 ditolak yang artinya ada hubungan tingkat pengetahuan ibu tentang IVA dengan perilaku ibu melakukan IVA. Kesimpulan penelitian ini adalah semakin baik tingkat pengetahuan ibu tentang IVA semkin baik perilaku ibu melakukan IVA. Diharapkan ibu untuk meningkatkan pengetahuan tentang IVA melalui media cetak dan elektronik dan untuk tenaga kesehatan selain memberikan penyuluhan tentang pemeriksaan IVA juga perlu diberikan motivasi pada ibu