Human induced pluripotent stem cell-derived sensory neurons for fate commitment of bone marrow-derived Schwann cells: Implications for re-myelination therapy

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Burden of upper gastrointestinal symptoms in patients prescribed dabigatran for stroke prevention

BACKGROUND: Dabigatran, a non-vitamin K antagonist oral anticoagulant, has been shown to prevent stroke in patients with non-valvular atrial fibrillation. Nonetheless, studies show that 10%-30% of those prescribed dabigatran experience dyspepsia that may eventually lead to discontinuation of therapy and loss of clinical benefit. AIM: To evaluate the gastrointestinal tolerability of dabigatran utilizing a validated questionnaire, as well as determining subsequent non-compliance and drug discontinuation. METHOD: This is an observational study. All patients were assessed by a validated questionnaire, Hong Kong dyspepsia index, prior to drug prescription and again 4 weeks later. RESULTS: In this study, 115 patients with non-valvular atrial fibrillation (mean age: 74.6 ± 11.4 years; mean CHA2DS2-VASc score was 3.39 ± 1.59) were prescribed dabigatran. At baseline, the mean Hong Kong dyspepsia index was 12.9 ± 1.6 and nine patients had significant dyspepsia (Hong Kong dyspepsia index ⩾ 16). After 4 weeks, the mean Hong Kong dyspepsia index was similar at 12.6 ± 1.9 (p = 0.23). There was no change in Hong Kong dyspepsia index after initiation of dabigatran in 59 (51.3%) patients, and improvement in 37 (32.2%). Only 19 (16.5%) patients had worsening of Hong Kong dyspepsia index, and among these 19 patients, only 1 patient (0.9%) discontinued dabigatran due to significant dyspepsia. CONCLUSION: Worsening of dyspepsia with dabigatran 110 mg twice daily was uncommon with correct drug administration and clear instructions provided. Systematic assessment of dyspeptic symptoms using a validated questionnaire (i.e. Hong Kong dyspepsia index) before and after treatment initiation allows a more objective comparison of dyspeptic symptoms

The in vitro effects of heat shock protein 65 kDa on proliferation of A7r5 smooth muscle cells

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ROC Analysis for Phase II Group Sequential Basket Clinical Trial

The basket trial is a recent development in the clinical trial practice. It conducts the test of the same treatment on several different related diseases in a single trial, and has the advantage of reduced cost and enhanced efficiency. A natural question is how to assess the performance of the group sequential basket trial against the classical group sequential trial? To our knowledge, a formal assessment hasn't been seen in the literature, and is the goal of this study. Specifically, we use the receiver operating characteristic curve to assess the performance of the mentioned two trials. We considered two cases, parametric and nonparametric settings. The former is efficient when the parametric model is correctly specified, but can bemis-leading if the model is incorrect; the latter is less efficient but is robust in that it cannot be wrong no matter what the true data generating model is. Simulation studies are conducted to evaluate the experiments, and it suggests that the group sequential basket trial generally outperforms the group sequential trial in either the parametric and nonparametric cases, and that the nonparametric method gives more accurate evaluation than the parametric one for moderate to large sample sizes

Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells

Transplantation of oligodendrocyte precursors represents a potential therapy for myelin disorders but requires a safe and accessible cell source. Here we report the directed differentiation of neural progenitors derived from adult bone marrow stromal cells (BMSCs) into oligodendrocyte precursors for cell therapy purpose. Neural progenitors among BMSCs could be culture expanded in non-adherent sphere-forming conditions and directed to differentiate along the oligodendrocyte lineage. BMSC-derived oligodendrocyte precursors (BM-OPs) differentiated into myelin basic protein (MBP)-positive oligodendrocyte when co-cultured with purified dorsal root ganglion (DRG) neurons. Injection of BM-OPs into the brain of myelin deficient Shiverer mice resulted in the generation of MBP-positive oligodendrocyte and compact myelin. Our results provided pointers to adult BMSCs as a readily accessible source of OPs towards cell therapy for myelin disorders.published_or_final_versio

ODE-methods in non-local equations

Non-local equations cannot be treated using classical ODE theorems. Nevertheless, several new methods have been introduced in the non-local gluing scheme of our previous article "On higher dimensional singularities for the fractional Yamabe problem: a non-local Mazzeo-Pacard program"; we survey and improve those, and present new applications as well. First, from the explicit symbol of the conformal fractional Laplacian, a variation of constants formula is obtained for fractional Hardy operators. We thus develop, in addition to a suitable extension in the spirit of Caffarelli--Silvestre, an equivalent formulation as an infinite system of second order constant coefficient ODEs. Classical ODE quantities like the Hamiltonian and Wro\'nskian may then be utilized. As applications, we obtain a Frobenius theorem and establish new Poho\vzaev identities. We also give a detailed proof for the non-degeneracy of the fast-decay singular solution of the fractional Lane-Emden equation.Comment: bibliography updated from previous versio

Cytokine profiles in patients with lower limb ischaemia

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