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Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

Background: The COVID-19 pandemic has had a tremendous impact on healthcare systems worldwide. In particular, long-term care facilities have proved more susceptible to infection as they care for vulnerable populations at high risk of chronic illness. How this impacts the role and core competencies of health and care workers in these facilities remains less understood., Aim: Describe how health and care workers contribute to the prevention of emerging infectious diseases in long-term care facilities., Design: A scoping review., Methods: A systematic search of literature dating from 2002 to 2022 was conducted in the following databases: EMBASE, Medline (Ovid), Cochrane Library, CINAHL Plus with Full Text (EBSCOhost), Web of Science, and AgeLine. Studies were selected if they focused on health and care workers in long-term care facilities, offered a perspective on the prevention of emerging infectious diseases or infection prevention and control, and were original qualitative or quantitative studies in English. Data were extracted, cross-checked and analyzed by two researchers, and any difference in views regarding the appropriateness of literature would be resolved by consulting a third researcher. An inductive descriptive approach was applied for the analysis of results, and themes were established via consensus meetings., Results: A total of fourteen studies from Asia, Europe, and the Americas were included. Three themes emerged from the review: "The roles of health and care workers evolve with the times", "The core competencies of health and care workers are essential for preventing emerging infectious diseases in long-term care facilities" and "The key to successful prevention of emerging infectious diseases in long-term care facilities is through a systematic, comprehensive effort that mobilize health and care workers at all levels". Health and care workers had to take on increasingly complex roles and rely on their core competencies to cope with epidemic changes, and facility resources, employee quality and management models were found to have significantly improved infection prevention and control outcomes., Conclusions: The roles of health and care workers are evolving, and effective infection prevention within long-term care facilities depends on their ability to perform core competencies with skill and confidence. Moreover, a systematic, comprehensive framework, for which this paper proposes three guidelines, is urgently needed to ensure consistent policy implementation within the facility as well as support and access to resources for health and care workers., Clinical Relevance: Infection prevention efforts within long-term care facilities must take into account the evolving roles of health and care workers, with a focus on guaranteeing access to resources, training and support that will help them gain the core competencies necessary for juggling those roles. In addition, there is an urgent need for research instruments that will help assess those competencies and identify areas of improvement., (© 2023 Sigma Theta Tau International.)

Emerging infectious diseases (EIDs) are a considerable threat to health, particularly in long-term care facilities (LTCFs), where residents are especially vulnerable. Nurses' competency in EID prevention is crucial to minimize the adverse effects of EIDs in LTCFs. This study investigated nurses' competency and related factors in EID prevention in LTCFs in Tainan, Taiwan. A cross-sectional design was employed, and nurses were recruited to complete an online survey examining the knowledge, attitude, and skills required to prevent EIDs in LTCFs. A total of 235 nurses completed the survey. The equivalent score index (SI) for knowledge regarding EID prevention was 68, indicating that the nurses did not have adequate knowledge regarding EID prevention. In contrast, the equivalent SI for the subscale of attitudes toward EID prevention was 78, indicating that the nurses exhibited moderately to highly positive attitudes toward EID prevention. However, they rated themselves as being highly skilled in EID prevention, corresponding to an equivalent SI of 91. Perceived supervisors' approval, marital status, attitudes toward EID prevention, EID prevention skills, knowledge regarding EIDs, and being in charge of infectious disease prevention were significant predictors of the nurses' competency. LTCF nurses, especially those working in nursing homes, should enhance their knowledge regarding EID prevention. These findings may help improve nurses' competency in preventing EIDs by encouraging the integration of practice strategies, education, research, and policy recommendations to eliminate EIDs in LTCFs.

Background: A major feature of the microenvironment in pancreatic ductal adenocarcinoma (PDAC) is the significant amount of extracellular matrix produced by pancreatic stellate cells (PSCs), which have been reported to enhance the invasiveness of pancreatic cancer cells and negatively impact the prognosis., Methods: We analyzed the data from two publicly available microarray datasets deposited in the Gene Expression Omnibus and found candidate genes that were differentially expressed in PDAC cells with metastatic potential and PDAC cells cocultured with PSCs. We studied the interaction between PDAC cells and PSCs in vitro and verified our finding with the survival data of patients with PDAC from the website of The Human Protein Atlas., Results: We found that PSCs stimulated PDAC cells to secrete S100A9, which attracted circulatory monocytes into cancer tissue and enhanced the expression of programmed death-ligand 1 (PD-L1) on macrophages. When analyzing the correlation of S100A9 and PD-L1 expression with the clinical outcomes of patients with PDAC, we ascertained that high expression of S100A9 and PD-L1 was associated with poor survival in patients with PDAC., Conclusions: PSCs stimulated PDAC cells to secrete S100A9, which acts as a chemoattractant to attract circulatory monocytes into cancer microenvironment and induces expression of PD-L1 on macrophages. High expression of S100A9 and PD-L1 was associated with worse overall survival in a cohort of patients with PDAC., (© 2021. The Author(s).)

Parkinson's disease (PD) is increasingly recognised as a systemic disorder in which inflammation might play a causative role rather than being a consequence or an epiphenomenon of the neurodegenerative process. Although growing genetic evidence links the central and peripheral immune system with both monogenic and sporadic PD, our understanding on how the immune system contributes to PD pathogenesis remains a daunting challenge. In this review, we discuss recent literature aimed at exploring the role of known genes and susceptibility loci to PD pathogenesis through immune system related mechanisms. Furthermore, we outline shared genetic etiologies and interrelations between PD and autoimmune diseases and underlining challenges and limitations faced in the translation of relevant allelic and regulatory risk loci to immune-pathological mechanisms. Lastly, with the field of immunogenetics expanding rapidly, we place these insights into a future context highlighting the prospect of immune modulation as a promising disease-modifying strategy.

Imatinib is a crucial therapeutic strategy against chronic myeloid leukemia. Though superficial edema is a common adverse effect of imatinib, massive fluid retention is rarely reported. Here, we report the case of an adolescent who had tolerated imatinib for a long time, and then presented with massive pleural/pericardial effusion during an episode of Campylobacter jejuni bacteremia. A stepwise and comprehensive survey excluded all other plausible causes of disease. The Naranjo scale was used to assess the probability of an adverse effect of medication, and the score turned out to be 9, indicating severe fluid retention to be a definite reaction to imatinib. Drug discontinuation, antibiotic administration, and invasive procedures improved this condition. After this episode, the patient could tolerate imatinib again, illustrating the transient and reversible nature of this reaction. Since prolonged imatinib usage is crucial for chronic myeloid leukemia control, alertness to drug-related adverse effects is recommended, even if the subject has previously shown a good tolerance to the drug due to various physical conditions, especially physiological stressors, like infection or inflammation., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The unique property of trehalose encourages its pharmaceutical application in aggregation-mediated neurodegenerative disorders, including Alzheimer's, Parkinson's, and many polyglutamine (polyQ)-mediated diseases. However, trehalose is digested into glucose by trehalase and which reduced its efficacy in the disease target tissues. Therefore, searching trehalase-indigestible analogs of trehalose is a potential strategy to enhance therapeutic effect. In this study, two trehalase-indigestible trehalose analogs, lactulose and melibiose, were selected through compound topology and functional group analyses. Hydrogen-bonding network analyses suggest that the elimination of the hydrogen bond between the linker ether and aspartate 321 (D321) of human trehalase is the key for lactulose and melibiose to avoid the hydrolyzation. Using polyQ-mediated spinocerebellar ataxia type 17 (SCA17) cell and slice cultures, we found the aggregation was significantly prohibited by trehalose, lactulose, and melibiose, which may through up-regulating of autophagy. These findings suggest the therapeutic applications of trehalase-indigestible trehalose analogs in aggregation-associated neurodegenerative diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In polyglutamine (polyQ)-mediated disorders, the expansion of translated CAG repeats in the disease genes result in long polyQ tracts in their respective proteins, leading to intracellular accumulation of aggregated polyQ proteins, production of reactive oxygen species, and cell death. The molecular chaperones act in preventing protein misfolding and aggregation, thus inhibiting a wide range of harmful downstream events. In the circumstance of accumulation of aggregated polyQ proteins, the autophagic pathway is induced to degrade the misfolded or aggregated proteins. In this study, we used Flp-In 293/SH-SY5Y cells with inducible SCA3 ATXN3/Q75-GFP expression to test the effect of indole and synthetic derivatives for neuroprotection. We found that ATXN3/Q75 aggregation can be significantly prohibited in Flp-In 293 cells by indole and derivative NC001-8. Meanwhile, indole and NC001-8 up-regulated chaperones and autophagy in the same cell models. Both of them further promote neurite outgrowth in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate how indole and derivative NC001-8 are likely to work in reduction of polyQ-aggregation and provide insight into the possible effectual mechanism of indole compounds in polyQ spinocerebellar ataxia (SCA) patients. These findings may have therapeutic applications in a broad range of clinical situations.

Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 as well as Huntington's disease are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyglutamine (polyQ) tract in the respective proteins. Evidence has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ proteins leads to apoptosis and cell death. Thus suppression of aggregate formation is expected to inhibit a wide range of downstream pathogenic events in polyQ diseases. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q75-GFP cells and applied this system to test the aqueous extract of Paeonia lactiflora (P. lactiflora) and its constituents. We found that the aggregation can be significantly prohibited by P. lactiflora and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to work on polyQ-aggregation reduction and provide insight into the possible working mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting point for screening more potential herbs for the treatment of SCA3 and other polyQ diseases.

Microfluidic chips require connections to larger macroscopic components, such as light sources, light detectors, and reagent reservoirs. In this article, we present novel methods for integrating capillaries, optical fibers, and wires with the channels of microfluidic chips. The method consists of forming planar interconnect channels in microfluidic chips and inserting capillaries, optical fibers, or wires into these channels. UV light is manually directed onto the ends of the interconnects using a microscope. UV-curable glue is then allowed to wick to the end of the capillaries, fibers, or wires, where it is cured to form rigid, liquid-tight connections. In a variant of this technique, used with light-guiding capillaries and optical fibers, the UV light is directed into the capillaries or fibers, and the UV-glue is cured by the cone of light emerging from the end of each capillary or fiber. This technique is fully self-aligned, greatly improves both the quality and the manufacturability of the interconnects, and has the potential to enable the fabrication of interconnects in a fully automated fashion. Using these methods, including a semi-automated implementation of the second technique, over 10,000 interconnects have been formed in almost 2000 microfluidic chips made of a variety of rigid materials. The resulting interconnects withstand pressures up to at least 800psi, have unswept volumes estimated to be less than 10 femtoliters, and have dead volumes defined only by the length of the capillary.

We measure the temperature and frequency dependence of the complex Hall angle for normal state YBa(2)Cu(3)O(7) films from dc to far-infrared frequencies (20-250 cm(-1)) using a new modulated polarization technique. We determine that the functional dependence of the Hall angle on scattering does not fit the expected Lorentzian response. We find spectral evidence supporting models of the Hall effect where the scattering Gamma(H) is linear in T, suggesting that a single relaxation rate, linear in temperature, governs transport in the cuprates.