Strategies for Continued Successful Treatment in Patients with Alzheimer's Disease : An Overview of Switching Between Pharmacological Agents

Altres ajuts: This review article is sponsored by Novartis Pharma K.K., Tokyo, Japan. The publication processing fees were funded by Novartis Pharma K.K., Tokyo, Japan.Alzheimer's disease (AD) is the most common cause of dementia, characterized by a progressive decline in cognition and function. Current treatment options for AD include the cholines-terase inhibitors (ChEIs) donepezil, galantamine, and rivastigmine, as well as the N-methyl-D-aspartate receptor antagonist memantine. Treatment guidelines recommend the use of ChEIs as the standard of care first-line therapy. Several randomized clinical studies have demonstrated the benefits of ChEIs on cogni-tion, global function, behavior and activities of daily living. However, patients may fail to achieve sus-tained clinical benefits from ChEIs due to lack/loss of efficacy and/or safety, tolerability issues, and poor adherence to the treatment. The purpose of this review is to explore the strategies for continued successful treatment in patients with AD. Literature search was performed for articles published in PubMed and MEDLINE, using pre-specified search terms. Articles were critically evaluated for inclusion based on their titles, abstracts, and full text of the publication. The findings of this review indicate that dose up-titration and switching between ChEIs may help to improve response to ChEI treatment and also address issues such as lack/loss of effica-cy or safety/tolerability in patients with AD. However, well-designed studies are needed to provide robust evidence

An investigation of fat-tailed distributions in fitting the Japanese stock market returns

The Tokyo Stock Exchange (TSE) is the fourth largest stock exchange in the world by aggregate market capitalization of its listed companies and largest in East Asia and Asia. It is of great importance for those in charge of managing risk to understand how its market index returns are distributed. The goal of this paper is to examine how various types of heavy-tailed distribution perform in risk management of the N225 Index returns. We compared these heavy-tailed distributions through a variety of criteria. Our results indicate the generalized hyperbolic distribution has the best goodness of fit and generates most suitable risk measures.peer-reviewe

Formation of lipid membrane‐incorporated small π‐molecules bearing hydrophilic groups

Nineteen poorly water‐soluble π‐conjugated molecules were evaluated in terms of their ability to be stably incorporated into lipid membranes. The resulting lipid membrane-incorporated π‐conjugated guest molecules (LMIGs) were classified into four categories, including (i) those that formed stable LMIGs; (ii) those where some of guest molecules precipitated; (iii) those that formed small self‐aggregates consisting of lipids and/or guest molecules; and (iv) those that leaked some of the guest molecules into the bulk water. Compounds belonging to category (ii) were confirmed by UV‐vis absorption analysis. In contrast, compounds belonging to categories (i), (iii) and (iv) were discriminated based on their 1H NMR spectra and the broadening or disappearance of the peaks of the guest molecules and the lipids in LMIGs and large liposomes. Several LMIGs could be converted from one category to another using other lipids. Furthermore, the guest molecules belonging to category (iv) were successfully predicted using the octanol‐water partition coefficient, which was calculated by simulation.This work was supported by the Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant‐in‐Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant‐in‐Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Lipid-membrane-incorporated arylboronate esters as agents for boron neutron capture therapy

Arylboronate esters bearing methyl groups in both of their ortho positions were stably incorporated into lipid membranes at high concentrations without undergoing hydrolysis to the corresponding boronic acids. This method could be used in combination with previous methods to increase the maximum ratio of boron atoms in liposomal boron carriers.This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Grant No. JP16H04133) and a Grant-in-Aid for Challenging Exploratory Research (Grant No. JP16K13982)

Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues

Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems

Effect of global atmospheric aerosol emission change on PM2.5-related health impacts

Background: Previous research has highlighted the importance of major atmospheric aerosols such as sulfate, through its precursor sulfur dioxide (SO2), black carbon (BC), and organic carbon (OC), and their effect on global climate regimes, specifically on their impact on particulate matter measuring <= 2.5 mu m (PM2.5). Policy regulations have attempted to address the change in these major active aerosols and their impact on PM2.5, which would presumably have a cascading effect toward the change of health risks. Objective: This study aimed to determine how the change in the global emissions of anthropogenic aerosols affects health, particularly through the change in attributable mortality (AN) and years of life lost (YLL). This study also aimed to explore the importance of using AM/YLL in conveying air pollution health impact message. Methods: The Model for Interdisciplinary Research on Climate was used to estimate the gridded atmospheric PM2.5 by changing the emission of SO2, BC, and OC. Next, the emissions were utilized to estimate the associated cause-specific risks via an integrated exposure-response function, and its consequent health indicators, AM and YLL, per country. Results: OC change yielded the greatest benefit for all country income groups, particularly among low-middle-income countries. Utilizing either AM or YLL did not alter the order of benefits among upper-middle and high-income countries (UMIC/HIC); however, using either health indicator to express the order of benefit varied among low- and low-middle-income countries (LIC/LMIC). Conclusions: Global and country-specific mitigation efforts focusing on OC-related activities would yield substantial health benefits. Substantial aerosol emission reduction would greatly benefit high-emitting countries (i.e. China and India). Although no difference is found in the order of health outcome benefits in UMIC/HIC, caution is warranted in using either AM or YLL for health impact assessment in LIC/LMIC