The Past, Present, and Future of Parkinson's Disease Treatment

Parkinson’s Disease was first introduced by James Parkinson in 1817. Since then, major strides have been made in the development of its treatment. Early treatments were dominated by traditional and complementary therapies, which were largely serendipitous and observation-based. Especially, the use of anticholinergics by Jean-Martin Charcot and his student Ordenstein prevailed in the late 20th century. Current drug-based therapies manifest in the form of levodopa accompanied by dopamine agonist, COMT inhibitor, or MAO-B inhibitor, for the purpose of reducing the levodopa-induced symptom fluctuation. In terms of surgical treatment, while ablative surgeries in the brain have been abandoned due to high mortality rate in the late 1900s, Deep Brain Stimulation in the subthalamic nucleus or internal globus pallidus has mostly replaced ablative surgeries since its introduction in 1987. Current research topics include non-dopaminergic agents for motor fluctuation reduction, transplantation of dopaminergic neurons, gene therapies using viral vectors, reduction of alpha-synuclein neurotoxicity, and neuroprotective therapies. Especially, due to the fact that the etiology of the disease is yet to be elucidated, neuroprotective therapies aimed at slowing or stopping disease progression are of particular interest. It is suggested that future research should aim towards clarifying the cause of the disease, for the development of a treatment that can permanently halt or reverse Parkinson’s Disease-related neurodegeneration

Designing brand chatbots: The impact of chatbot’s personality on the user’s brand personality perception

Along with advancements in technologies, which include machine learning and artificial intelligence, chatbots are increasingly taking the place of employees that work as customer service agents and personal shoppers. Considering that the characteristics of employees can influence a consumer’s perception of brand personality (Aaker, 1997), this perception may also be affected by the chatbot’s personality. This paper aims to investigate the impact of a chatbot’s personality on a user’s perception of brand personality. Two brands, and their chatbots, are used as case studies. The empirical study comprises of two stages, in which the qualitative and the quantitative data are both gathered and analyzed. Firstly, an online survey was conducted to investigate the personalities of two existing brands and their respective chatbots. As a result, a gap in personality between one of the brands and its chatbot was identified. Next, two prototypes were built and then tested in the interview. One was the emulator of the current brand chatbot, and the other was a new chatbot designed to have a personality closer to the brand personality. The findings reveal that the chatbot’s personality may affect brand personality, even though the impact was smaller than expected because participants perceived that the two prototypes’ personalities were moderately close to the brand personality. Interestingly, interviewees revealed that the chatbot’s personality may have a greater influence if it is totally different from the brand personality. Based on the study findings, design considerations are suggested to help practitioners in designing brand chatbots

Rapid toxicity assessment of six antifouling booster biocides using a microplate-based chlorophyll fluorescence in Undaria pinnatifida gametophytes

Biocides of antifouling agents can cause problems in marine ecosystems by damaging to non-target algal species. Aquatic bioassays are important means of assessing the quality of water containing mixtures of contaminants and of providing a safety standard for water management in an ecological context. In this study, a rapid, sensitive and inexpensive test method was developed using free-living male and female gametophytes of the brown macroalga Undaria pinnatifida. A conventional fluorometer was employed to evaluate the acute (48 h) toxic effects of six antifouling biocides: 4,5-Dichloro-2-octyl-isothiazolone (DCOIT), diuron, irgarol, medetomidine, tolylfluanid, zinc pyrithione (ZnPT). The decreasing toxicity in male and female gametophytes as estimated by EC50 (effective concentration at which 50% inhibition occurs) values was: diuron (0.037 and 0.128 mg l(-1), respectively) > irgarol (0.096 and 0.172 mg l(-1), respectively) > tolylfluanid (0.238 and 1.028 mg l(-1), respectively) > DCOIT (1.015 and 0.890 mg l(-1), respectively) > medetomidine (12.032 and 12.763 mg l(-1), respectively). For ZnPT, 50% fluorescence inhibition of U. pinnatifida gametophytes occurred at concentrations above 0.4 mg l(-1). The Undaria method is rapid, simple, practical, and cost-effective for the detection of photosynthesis-inhibiting biocides, thus making a useful tool for testing the toxicity of antifouling agents in marine environments

The Development of an Inducible Akt as a Potential Gene Therapy for Parkinson’s Disease

Parkinson’s disease remains a major neurodegenerative disease with prevalence that is second only to Alzheimer’s disease. Despite much advancement in the understanding of the pathogenesis of Parkinson’s disease, current therapeutic options are limited to those that are only symptomatic and are not disease-modifying. Furthermore, due to what seems to be increasingly complex underlying mechanisms of the disease, identifying a broadly applicable therapeutic strategy is difficult. There is much evidence surrounding the role of apoptosis and conversely, dysfunction of anti-apoptotic signaling in the progressive neurodegeneration that causes Parkinson’s disease. In particular, suppressed PI3K signaling has been implicated in the literature as a key event that occurs during neurodegeneration. Thus, regardless of the diverse upstream mechanisms that may lead to the disease, targeting a downstream effector of neuronal survival presents a therapeutic strategy that may be broadly effective against Parkinson’s disease. For this dissertation, we have developed a method to control the levels of active Akt, the main mediator of the PI3K signaling pathway, using an innovative protein destabilizing technique to create an inducible Akt, DD-Akt(E40K). This method permits the control of active Akt levels through a commonly used and blood-brain barrier permeable antibiotic, Trimethoprim. We have successfully established the inducibility of DD-Akt(E40K) across various cellular contexts, including neuronal cell types and conditions with suppressed PI3K signaling. This inducibility was found to be dose-responsive to Trimethoprim, reversible, and able to induce a known downstream substrate, FoxO4, that is an important regulator of cell survival. Importantly, DD-Akt(E40K) was found to inducibly protect neuronal PC12 cells against Parkinson’s disease mimetic toxins as well as growth-factor removal, indicating a proof of principle for the targeting of Akt activity as a protective strategy against Parkinson’s disease. The reported trophic effects of active Akt were also corroborated using our inducible DD-Akt(E40K) system in vivo, demonstrating significant increases in neuronal cell size within the substantia nigra of mice. Intriguingly, the inducibility of DD-Akt(E40K) was found to be dependent on the region of expression in the brain of mice such that the levels of this protective protein were not controllable by Trimethoprim in the substantia nigra but were controllable in the striatum. Taken together, the studies presented in this dissertation establish a new tool for the study of Akt signaling in various cellular and disease contexts and validate Akt as a promising therapeutic target in Parkinson’s disease. Our results also suggest an intriguing mechanism for the underlying pathology and selective degeneration observed in the disease

Do caregivers’ involvement in Type 2 diabetes education affect patients’ health outcomes?: A systematic review and meta-analysis

Introduction: The prevalence of Type 2 diabetes mellitus (T2DM) is rising worldwide. Patients frequently struggle with controlling their diabetes and need the assistance of caregivers for effective self-management because managing diabetes requires a variety of strategies, including diet, glucose monitoring, and exercise. This study aimed to examine the effect of caregiver involvement in T2DM education within a community on patients’ diabetes care outcomes. Methods: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of all published studies from the earliest record to May 2022 that reported adult caregivers of T2DM patients who participated in educational interventions concerning diabetes management and that reported one or more outcomes of the interventions were conducted. Four databases were used, including PubMed, Cochrane Library, EMBASE, and CINAHL. The meta-analysis focused on glycated hemoglobin (HbA1c) levels among randomized controlled trials (RCTs), with additional attention to lipid levels. Review Manager 5.4 was used to perform this meta-analysis. Results: A total of 17 out of 683 studies were synthesized. Involvement of caregivers in T2DM education is shown to reduce body mass index and HbA1c. This involvement also improves patients’ knowledge, physical activity, and self-efficacy, but the effect on medication adherence varies. A meta-analysis of six RCT studies shows that caregiver involvement in T2DM education reduced pooled HbA1c levels by 0.83 (95% Confidence interval: −1.27–−0.38) compared to involvement (p = 0.0003). Meta-analysis of three types of lipids (low-density lipoprotein, total cholesterol, and high-density lipoprotein) showed no strong evidence that caregiver participation in diabetes education improved lipid levels. Conclusions: Caregivers play key roles in diabetes management and can contribute to improving patient HbA1c levels. Future research should focus on enhancing caregiver participation in T2DM education

Structured electrode additive manufacturing for lithium-ion batteries

A thick electrode with high areal capacity has been developed as a strategy for high-energy-density lithium-ion batteries, but thick electrodes have difficulties in manufacturing and limitations in ion transport. Here, we reported a new manufacturing approach for ultra-thick electrode with aligned structure, called structure electrode additive manufacturing or SEAM, which aligns active materials to the through-thicknesses direction of electrodes using shear flow and a designed printing path. The ultra-thick electrodes with high loading of active materials, low tortuous structure, and good structure stability resulting from a simple and scalable SEAM lead to rapid ion transport and fast electrolyte infusion, delivering a higher areal capacity than slurry-casted thick electrodes. SEAM shows strengths in design flexibility and scalability, which allows the production of practical high energy/power density structure electrodes