Dry Eye Therapy Using Cannabinoid Ligands

Dry eye disease (DED) has a high prevalence (up to 50% in some communities) with increasing incidence. Notably, patients have such high morbidity and burden that they desperately need effective treatment. However, as a "multifactorial disease," DED consists of various complex disorders, all of which interact to form a vicious circle and obscure the etiology. Even though physicians and patients have different therapeutic options, the common disadvantages in current treatments are (i) a lack of compliance due to an overload of products, (ii) the occurrence of side effects of different drugs, and (iii) limited efficiency in some particular cases. As a result, DED requires a novel therapy capable of simultaneously addressing multiple targets in DED pathogenesis. To find suitable targets and candidates for DED, the endocannabinoid system (ECS) and its receptors (CBRs) present at the ocular surface are a promising choice, as ECS functions are involved in a plethora of physical processes. Experimental evidence showed that using CBRs ligands can modulate anti-inflammatory, neurosensory, and wound-healing processes, which are potential to control and prevent DED pathogenesis and the vicious circle. Therefore, this study was carried out to determine whether CBR ligand eye drops can provide a multiple-target therapy for DED. The project hereby consisted of three parts, addressing consecutive objectives: Firstly, this study confirms the involvement of CBRs (in particular, CB1R and CB2R) in DED pathomechanism based on an experimental DED mouse model (desiccating stress model). CB1R and CB2R were detected by RT-qPCR and in-situ hybridization techniques in the cornea, conjunctiva, and lacrimal glands. During DED-induction, CB1R and CB2R expressions were increasing, concurrent with significant DED phenotypes (low tear production, high score of cornea epitheliopathy, and reduced cornea sensitivity). Furthermore, different CBRs ligands were topically applied to DED-induced mice. CBRs therapy suppressed the increasing trend of CBR expression, which coincided with improved phenotype readouts. Tetrahydrocannabinol (THC) is a promising candidate for anti-inflammatory effects, together with protecting nerve morphology and maintaining corneal sensitivity. Secondly, an in-vitro wound-healing model was developed to characterize the influence of CBR on the re-epithelialization process. Interestingly, while CB1R was found to have a significant effect, selective CB2R ligand did not influence the re-epithelialization. In detail, activating CB1R improved the wound-healing rate while selectively inhibiting CB1R delayed the wound-healing process. Furthermore, tetrahydrocannabinol (THC), a non-selective agonist, showed a biphasic effect: high concentration (from 1 to 10 µM) delayed wound healing, while low concentration (from 0.01 to 0.5 µM) increased the rate. This finding supports the functional role of CBRs in DED pathogenesis and management. Thirdly, we proposed two eyedrop formulations for THC, in which THC was formulated in the form of micelle in water at the nanoscale (around 10nm). All ingredients are already used in pharmaceuticals and bio-products, so the formulations are expected to be safe and well-tolerated. Additionally, the formulation steps are feasible with low technical complexity, showing promise for commercial scaling-up. The finally proposed formulation contains 0.5% THC, adequate to provide a significant effect, as shown in the in-vivo model in the first part. Also, the obtained results confirmed stability when stored at room temperature or refrigerator (4-8oC), facilitating its use by patients. In summary, this study confirmed the potentiality of CBR and CBR ligands, notably THC, as a multiple-target therapy for dry eye patients

Rigorous derivation of Michaelis-Menten kinetics in the presence of diffusion

Reactions with enzymes are critical in biochemistry, where the enzymes act as catalysis in the process. One of the most used mechanisms for modeling enzyme-catalyzed reactions is the Michaelis-Menten (MM) kinetic. In the ODE level, i.e. concentrations are only on time-dependent, this kinetic can be rigorously derived from mass action law using quasi-steady-state approximation. This issue in the PDE setting, for instance when molecular diffusion is taken into account, is considerably more challenging and only formal derivations have been established. In this paper, we prove this derivation rigorously and obtain MM kinetic in the presence of spatial diffusion. In particular, we show that, in general, the reduced problem is a cross-diffusion-reaction system. Our proof is based on improved duality method, heat regularisation and a suitable modified energy function. To the best of our knowledge, this work provides the first rigorous derivation of MM kinetic from mass action kinetic in the PDE setting.Comment: Comments are welcome

On initial value and terminal value problems for subdiffusive stochastic Rayleigh-Stokes equation

In this paper, we study two stochastic problems for time-fractional RayleighStokes equation including the initial value problem and the terminal value problem. Here, two problems are perturbed by Wiener process, the fractional derivative are taken in the sense of Riemann-Liouville, the source function and the time-spatial noise are nonlinear and satisfy the globally Lipschitz conditions. We attempt to give some existence results and regularity properties for the mild solution of each problem

On stochastic nonclassical diffusion equation with standard and fractional Brownian motion

This paper is concerned with the mathematical analysis of terminal value problems for a stochastic non-classical diffusion equation, where the source is assumed to be driven by classical and fractional Brownian motions. Our two problems are to study in the sense of well-posedness and ill-posedness meanings. Here, a terminal value problem is a problem of determining the statistical properties of the initial data from the final time data. In the case 0 < β ≤ 1, where β is the fractional order of a Laplace operator, we show that these are well-posed under certain assumptions. We state a definition of ill-posedness and obtain the ill-poseness results for the problems when β > 1. The major analysis tools in this paper are based on properties of stochastic integrals with respect to the fractional Brownian motion

STUDENT EVALUATION OF TEACHING EFFECTIVENESS: AN INVESTIGATION INTO TEACHERS’ AND STUDENTS’ PERCEPTIONS

This descriptive study aims to investigate how EFL teachers and EFL students perceive Student Evaluation of Teaching Effectiveness (SETE) as well as to seek for possible similarities and differences between the two groups’ perceptions. The current study was conducted with the participation of 60 teachers and 100 students at an EFL Language Center in the Mekong Delta, Vietnam. Quantitative and qualitative data were collected via questionnaires and semi-structured interviews. Main findings reveal that: (1) almost all teachers and students are highly aware of SETE in relation to its necessity and benefits except for its validity and reliability; (2) the two groups of participants acknowledged their frequent participation in SETE and expressed their preferences for certain SETE procedures; (3) there are major similarities and differences between teachers’ and students’ perceptions of SETE.  Article visualizations

Students' Views of Art Education as Their Future Career

Art has long been an important subject of the education system. In Vietnam, teaching arts is taken a solid position as a subject of the education system from primary to tertiary education level. However, little is known about the situation and the need for transformation in the way students are trained to become art teachers. To clarify the view and attitudes of the to-be-an-art-teacher students, we conducted an online survey to collect data from students who enrolled in the bachelor course, majoring in art teaching at a university in Vietnam. A total of 57 students participated in the survey, most of them are females in the second year of the on-the-job B.A. course. The results showed that the respondents reported needing more diversified learning content such as applied arts, installation, and multimedia. They showed a need to have more practice sessions and fieldwork such as visiting museums and exhibitions. The respondents specified that they chose this major because they love the subject and love teaching, as well as to address the social need of learning arts, as arts seem to be a more important subject for elementary education. They shared a positive attitude toward the internationalization of local art education, however, none of them plan to study abroad. These findings imply the need for improving the quality of teaching and internationalization of art teacher education to meet international standards in the context of a developing country