Mucopolysaccharidoses I and II: Brief Review of Therapeutic Options and Supportive/Palliative Therapies.

Purpose. Mucopolysaccharidoses (MPS) are group of inherited lysosomal storage diseases caused by mutations of enzymes involved in catalyzing different glycosaminoglycans (GAGs). MPS I and MPS II exhibit both somatic and neurological symptoms with a relatively high disease incidence. Hematopoietic stem cell therapy (HSCT) and intravenous enzyme replacement therapy (ERT) have had a significant impact on the treatment and comprehension of disease. This review is aimed at providing a comprehensive evaluation of the pros and cons of HSCT and ERT, as well as an up-to-date knowledge of new drugs under development. In addition, multiple disease management strategies for the uncontrollable manifestations of MPS I and MPS II to improve patients' quality of life are presented. Findings. Natural history of MPS I and MPS II shows that somatic and neurological symptoms occur earlier in severe forms of MPS I than in MPS II. ERT increases life expectancy and alleviates some of the somatic symptoms, but musculoskeletal, ophthalmological, and central nervous system (CNS) manifestations are not controlled. Additionally, life-long treatment burdens and immunogenicity restriction are unintended consequences of ERT application. HSCT, another treatment method, is effective in controlling the CNS symptoms and hence has been adopted as the standard treatment for severe types of MPS I. However, it is ineffective in MPS II, which can be explained by the relatively late diagnosis. In addition, several factors such as transplant age limits or graft-versus-host disease in HSCT have limited its application for patients. Novel therapies, including BBB-penetrable-ERT, gene therapy, and substrate reduction therapy, are under development to control currently unmanageable manifestations. BBB-penetrable-ERT is being studied comprehensively in the hopes of being used in the near future as a method to effectively control CNS symptoms. Gene therapy has the potential to "cure" the disease with a one-time treatment rather than just alleviate symptoms, which makes it an attractive treatment strategy. Several clinical studies on gene therapy reveal that delivering genes directly into the brain achieves better results than intravenous administration in patients with neurological symptoms. Considering new drugs are still in clinical stage, disease management with close monitoring and supportive/palliative therapy is of great importance for the time being. Proper rehabilitation therapy, including physical and occupational therapy, surgical intervention, or medications, can benefit patients with uncontrolled musculoskeletal, respiratory, ophthalmological, and neurological manifestations.

Correlation Length in Concentrated Electrolytes: Insights from All-Atom Molecular Dynamics Simulations.

We study the correlation length of the charge-charge pair correlations in concentrated electrolyte solutions by means of all-atom, explicit-solvent molecular dynamics simulations. We investigate LiCl and NaI in water, which constitute highly soluble, prototypical salts for experiments, as well as two more complex, molecular electrolyte systems of lithium bis(trifluoromethane)sulfonimide (LiTFSI), a salt commonly employed in electrochemical storage systems, in water, and in an organic solvent mixture of dimethoxyethane and dioxolane. Our simulations support the recent experimental observations as well as theoretical predictions of a nonmonotonic behavior of the correlation length with increasing salt concentration. We observe a Debye-Hückel like regime at low concentration, followed by a minimum reached when d/λD ≃ 1, where λD is the Debye correlation length and d is the effective ionic diameter, and an increasing correlation length with salt concentration in very concentrated electrolytes. As in the experiments, we find that the screening length in the concentrated regime follows a universal scaling law as a function d/λD for all studied salts. However, the scaling exponent is significantly lower than the experimentally measured one and lies in the range of the theoretical predictions based on much simpler electrolyte models.

Effects of Whole-Body Vibration on Upper Extremity Function and Grip Strength in Patients with Subacute Stroke: A Randomised Single-Blind Controlled Trial.

BACKGROUND: Whole-body vibration has been used to improve motor function in chronic stroke patients, but its effect on patients with subacute strokes remains unclear. OBJECTIVES: We explored the effect of whole-body vibration on patients with subacute strokes. METHODS: Participants were randomly allocated to a whole-body vibration (WBV) group (n = 30) or an upper- and lower-cycle (ULC) group (n = 30). Both groups received occupational therapy after these interventions. All participants received treatment for 30 min/day, 5 days/week, for 4 weeks. Both groups received the same conventional physical therapy. RESULTS: The manual function test (MFT) score and grip strength improved after both WBV (p = 0.001 and p = 0.001, respectively) and ULC (p = 0.002 and p = 0.001, respectively), but the improvement was more pronounced (MFT p = 0.016; GS p = 0.023) after WBV. CONCLUSIONS: These findings suggest that the use of WBV and ULC was effective as remedial treatments for improving upper extremity motor function and increasing grip strength for patients with subacute strokes. The improvement was more pronounced for the WBV treatment. This trial is registered with KCT0003246.

Chasing Aqueous Biphasic Systems from Simple Salts by Exploring the LiTFSI/LiCl/H2O Phase Diagram.

Aqueous biphasic systems (ABSs), in which two aqueous phases with different compositions coexist as separate liquids, were first reported more than a century ago with polymer solutions. Recent observations of ABS forming from concentrated mixtures of inorganic salts and ionic liquids raise the fundamental question of how "different" the components of such mixtures should be for a liquid-liquid phase separation to occur. Here we show that even two monovalent salts sharing a common cation (lithium) but with different anions, namely, LiCl and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), may result in the formation of ABSs over a wide range of compositions at room temperature. Using a combination of experimental techniques and molecular simulations, we analyze the coexistence diagram and the mechanism driving the phase separation, arising from the different anion sizes. The understanding and control of ABS may provide new avenues for aqueous-based battery systems.