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Hyposmia is one of the cardinal symptoms of Parkinson’s disease (PD), with a considerably high prevalence rate in PD individuals. However, some individuals still retain normal olfactory function. Recent studies have shown that genetic factors may play a role in such a phenomenon. This study aimed to explore the potential genetic factors underlying the variation of olfactory function among PD individuals. Two hundred and three Han Chinese individuals with PD were recruited into this study. All the individuals underwent detailed clinical assessment conducted by experienced neurologists. High-throughput sequencing was performed to identify gene variants associated with PD. TAAR5, OR6C70, and GBA were included in the association analysis. In our study, 85 out of 203 individuals (41.9%) reported normal olfaction, and the other 118 (58.1%) reported hyposmia. Genotype and allele logistic regression models were applied to association analysis. We did not find any significant association of TAAR5 and OR6C70 with hyposmia. However, we found that GBA rs762488 was associated with increased hyposmia risk (P = 0.036, OR = 3.05, 95% CI = 1.08–8.63), while GBA rs1800438 was associated with decreased hyposmia risk (P = 0.032, OR = 0.47, 95% CI = 0.24–0.94). In conclusion, this study revealed the association of GBA with hyposmia, indicating the genetic involvement in PD hyposmia variation. However, we did not replicate previous results (TAAR5 and OR6C70) in this study. Further studies with larger sample sizes in different populations are warranted.

Yi-Lun Ge,1,&ast; Si-Yi Gong,1,&ast; Pu-Zhi Wang,1 Jia-Hui Yan,1 Wen Li,1 Jin-Ru Zhang,1 Hong Jin,1 Sheng Zhuang,1 Lei Hu,2 Chang-Wei Ding,2 Ya-Ping Yang,1 Fen Wang,3 Dan Li,4 Jing Chen,1 Cheng-Jie Mao,1,4 Ying-Chun Zhang,2 Kai Li,1 Chun-Feng Liu1,3,4 1Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Li, Department of Neurology, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, People’s Republic of China, Tel +86-512-6778-4179, Fax +86-512-6828-4303, Email liskai@126.comPurpose: Cognitive impairment (CI) is a common but debilitating non-motor symptom in Parkinson’s disease (PD). Although cerebrovascular functions are related to cognitive performance in healthy individuals, such a relation in PD remains elusive. This study aims to assess the association between cerebrovascular function and cognitive performance in PD individuals.Patients and Methods: Two-hundred-and-one PD individuals were retrospectively included. They were subsequently divided into two groups: PD with normal cognition (PD-NC) and PD with CI (PD-CI). Cerebral hemodynamic characteristics of the middle cerebral arteries were assessed by transcranial ultrasound. The association between scores in each cognitive domain and cerebral hemodynamic parameters was further analyzed using regression analyses. Additionally, a binary logistic regression model with backward stepwise procedure was applied to build the model for discriminating CI in PD individuals. An independent dataset of additional 46 PD individuals was used further.Results: The PD-CI group showed a relatively lower end-diastolic blood flow velocity (EDV, p < 0.05) and a higher resistive index (RI, p < 0.05) compared to the PD-NC group. RI showed significant associations with the memory item score of Montreal Cognitive Assessment (p < 0.05). A model combining clinical and hemodynamic variables was established with optimal efficiency (area under the curve, AUC = 0.651). Further replication of the model in an independent dataset yielded a great consistency (AUC = 0.704).Conclusion: In our study, cerebrovascular functions were significantly associated with the cognitive performance in PD individuals, especially with the memory task. The established model was effective in identifying CI in PD individuals, which might be a potentially useful tool to screen the cognitive decline in PD individuals at an early stage of the disease. Further studies with larger sample sizes in different populations are warranted.Keywords: Parkinson’s disease, cognitive impairment, transcranial ultrasound, resistive index

In this paper, the synthesis of 2,4,6-trinitrophenol from phenol was improved in the range of 0–65°C, and the yield was 79.4%. The effectiveness of the synthesis process was confirmed by Nuclear Ma...

Neuroinflammation mediated by microglia plays a key role in the pathogenesis of Parkinson's disease (PD), and our previous studies showed this was significantly inhibited by enhanced autophagy. In the autophagy pathway, Bcl2-associated athanogene (BAG)3 is a prominent co-chaperone, and we have shown BAG3 can regulate autophagy to clear the PD pathogenic protein α-synuclein. However, the connection between BAG3 and microglia mediated neuroinflammation is not clear.In this study, we explored whether BAG3 regulated related neuroinflammation and its original mechanism in PD. An inflammatory model of PD was established by injecting adeno-associated virus (AAV)-BAG3 into the bilateral striatum of C57BL/6 male mice to induce overexpression of BAG3, followed by injection of lipopolysaccharide (LPS). The striatum was extracted at 3 days after injection of LPS for Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemical staining was performed at 21 days after injection. At the same time, LPS was used to induce activation of BV2 cells to verify the effect of BAG3Overexpression of BAG3 reduced LPS-induced pyroptosis by reducing activation of caspase-1, the NOD-like receptor family, and the pyrin domain-containing 3 (NLRP3) inflammasome, and by release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The LPS-induced inflammatory environment inhibits autophagy, and overexpression of BAG3 can restore autophagy, which may be the mechanism by which BAG3 reduces neuronal inflammation in PD.Our results demonstrate BAG3 promotes autophagy and suppresses NLRP3 inflammasome formation in PD.

Aims and objectives Research examining the effectiveness of resistance band exercises for improving physical and psychological dimensions among frail older adults has been inconsistent. We aimed to examine the effects of resistance band exercises for improving outcomes in frail older adults. Background To provide robust evidence regarding the effectiveness of resistance band exercises and explore other potential outcomes in frail older adults, a systematic review of RCTs remains necessary. Design Systematic literature review and meta-analysis were conducted in accordance with the PRISMA guidelines. Methods Four databases were searched. English language papers were retrieved from 2006 to 2020. Three reviewers reviewed the methodology of the selected studies using the Joanna Briggs Institute tool for randomised controlled trials. The pooled standardised mean difference was calculated using a random-effects model. Heterogeneity among pooled studies was assessed using the τ2 , Q and I2 statistics, and publication bias was evaluated using Egger's test and the visual inspection of funnel plots. Results A total of 15 studies met the eligibility criteria for this study. Overall, resistance band exercise reduced frailty after 24 weeks (SMD: -0.29; 95% CI: -0.55 to -0.03) and reduced depression after both 12 weeks (SMD: -0.19; 95% CI: -0.38 to -0.01) and 24 weeks (SMD: -0.30; 95% CI: -0.52 to -0.09). However, no significant effects were observed for frailty after 12 weeks, and no significant effects were observed for grip strength, leg strength, activities of daily living or quality of life at any time. Conclusion Resistance band exercise might be considered a viable strategy for frail older adults in the community or in long-term care facilities. More research implementing a standardised protocol remains necessary to identify the effects of different training volumes and the dose-response relationship for the very old and frail population. Relevance to clinical practice As a safe complementary intervention for frail older adults, health providers should consider resistance band exercises when caring for frail older adults because this intervention has clinical benefits.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson disease (PD). Abnormal substantia nigra hyperechogenicity (SN+), detected by transcranial sonography (TCS), plays an important role in the differential diagnosis of PD. The purpose of this study was to investigate the predictive performance of quantitative SN+ evaluations for LID. Five hundred sixty-two individuals were included in our analysis, and 198 individuals were followed up. These individuals were divided into two groups at baseline: the PD with LID (PD+LID) group and the PD without LID (PD-LID) group. The association between total hyperechogenic area of the SN on both sides (SN

We explore the influence of the artificial atomic chain on the input-output relation of the cavity. Specifically, we extend the atom chain to the one-dimensional Su-Schrieffer-Heeger (SSH) chain to check the role of atomic topological non-trivial edge state on the transmission characteristics of the cavity. The superconducting circuits can realize the artificial atomic chain. Our results show that the atom chain is not equivalent to atom gas, and the transmission properties of the cavity containing the atom chain are entirely different from that of the cavity containing atom gas. When the atom chain is arranged in the form of topological non-trivial SSH model, the atom chain can be equivalent to the three-level atom, in which the edge state contributes to the second level and is resonant with the cavity, while the high-energy bulk state contributes to form the third level and is greatly detuned with the cavity. Therefore, the transmission spectrum shows no more than three peaks. This allows us to infer the topological phase of the atomic chain and the coupling strength between the atom and the cavity only from the profile of the transmission spectrum. Our work is helping to understand the role of topology in quantum optics.

Inflammation is one of the pathogenic processes in Parkinson’s disease (PD). Dopamine receptor agonist pramipexole (PPX) is extensively used for PD treatment in clinics. A number of studies show that PPX exerts neuroprotection on dopaminergic (DA) neurons, but the molecular mechanisms underlying the protective effects of PPX on DA neurons are not fully elucidated. In the present study, we investigated whether PPX modulated PD-related neuroinflammation and underlying mechanisms. PD model was established in mice by bilateral striatum injection of lipopolyssaccharide (LPS). The mice were administered PPX (0.5 mg·kg−1·d−1, i.p.) 3 days before LPS injection, and for 3 or 21 days after surgery, respectively, for biochemical and histological analyses. We showed that PPX administration significantly alleviated the loss of DA neurons, and suppressed the astrocyte activation and levels of proinflammatory cytokine IL-1β in the substantia nigra of LPS-injected mice. Furthermore, PPX administration significantly decreased the expression of NLRP3 inflammasome-associated proteins, i.e., cleaved forms of caspase-1, IL-1β, and apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) in the striatum. These results were validated in LPS+ATP-stimulated primary mouse astrocytes in vitro. Remarkably, we showed that PPX (100–400 μM) dose-dependently enhanced the autophagy activity in the astrocytes evidenced by the elevations in LC3-II and BECN1 protein expression, as well as the increase of GFP-LC3 puncta formation. The opposite effects of PPX on astrocytic NLRP3 inflammasome and autophagy were eliminated by Drd3 depletion. Moreover, we demonstrated that both pretreatment of astrocytes with autophagy inhibitor chloroquine (40 μM) in vitro and astrocyte-specific Atg5 knockdown in vivo blocked PPX-caused inhibition on NLRP3 inflammasome and protection against DA neuron damage. Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy.

The cell‐to‐cell transfer of α‐synuclein (α‐Syn) greatly contributes to Parkinson's disease (PD) pathogenesis and underlies the spread of α‐Syn pathology. During this process, extracellular α‐Syn can activate microglia and neuroinflammation, which plays an important role in PD. However, the effect of extracellular α‐Syn on microglia autophagy is poorly understood. In the present study, we reported that extracellular α‐Syn inhibited the autophagy initiation, as indicated by LC3‐II reduction and p62 protein elevation in BV2 and cultured primary microglia. The in vitro findings were verified in microglia‐enriched population isolated from α‐Syn‐overexpressing mice induced by adeno‐associated virus (AAV2/9)‐encoded wildtype human α‐Syn injection into the substantia nigra (SN). Mechanistically, α‐Syn led to microglial autophagic impairment through activating toll‐like receptor 4 (Tlr4) and its downstream p38 and Akt‐mTOR signaling because Tlr4 knockout and inhibition of p38, Akt as well as mTOR prevented α‐Syn‐induced autophagy inhibition. Moreover, inhibition of Akt reversed the mTOR activation but failed to affect p38 phosphorylation triggered by α‐Syn. Functionally, the in vivo evidence showed that lysozyme 2 Cre (Lyz2 cre)‐mediated depletion of autophagy‐related gene 5 (Atg5) in microglia aggravated the neuroinflammation and dopaminergic neuron losses in the SN and exacerbated the locomotor deficit in α‐Syn‐overexpressing mice. Taken together, the results suggest that extracellular α‐Syn, via Tlr4‐dependent p38 and Akt‐mTOR signaling cascades, disrupts microglial autophagy activity which synergistically contributes to neuroinflammation and PD development., Autophagy‐dependent and independent machinery synergistically contribute to hα‐Syn‐caused neuroinflammation in PD. The basal autophagy activity restricts microglia inflammation. Extracellular hα‐Syn interacts with and activates Tlr4, resulting in inflammatory responses, as well as autophagy suppression in microglia via Tlr4‐dependent p38 and Akt/mTOR signaling cascades. This impairs the inhibitory effect of autophagy on inflammation, and thus aggravating hα‐Syn‐induced inflammatory responses.

Autophagy is a catabolic process that removes aggregated proteins and damaged organelles via lysosomal degradation. Increasing evidence suggests that dysfunction of autophagy is associated with a variety of human pathologies, including aging, cancer, neurodegenerative diseases, heart diseases, diabetes, and other metabolic diseases. Current research suggests that the regulation of autophagy may be a novel target for the treatment of these diseases. For this purpose, it is essential to have a deep understanding on the molecular details of autophagy and its regulatory network in each of the disease contexts. Over the years, a variety of chemical autophagy inducers and inhibitors has been developed. The application of these autophagy regulators can assist us in the exploration of the mechanism and therapeutic potential of autophagy regulation. In this chapter, we summarize the recent advances in chemical autophagy regulators to provide methodological support for autophagy research.

In recent years, the prosperous electric vehicle industry has contributed to the rapid development of lithium-ion batteries. However, the increase in the energy density of lithium-ion batteries has also created more pressing safety concerns. The emergence of a new flame-retardant material with the additive ethoxy (pentafluoro) cyclotriphosphazene can ameliorate the performance of lithium-ion batteries while ensuring their safety. The present study proposes a new polymer composite flame-retardant electrolyte and adopts differential scanning calorimetry (DSC) and accelerating rate calorimetry to investigate its thermal effect. The study found that the heating rate is positively correlated with the onset temperature, peak temperature, and endset temperature of the endothermic peak. The flame-retardant modified polymer electrolyte for new lithium-ion batteries has better thermal stability than traditional lithium-ion battery electrolytes. Three non-isothermal methods (Kissinger, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa) were also used to calculate the kinetic parameters based on the DSC experimental data. The apparent activation energy results of the three non-isothermal methods were averaged as 54.16 kJ/mol. The research results can provide valuable references for the selection and preparation of flame-retardant additives in lithium-ion batteries.

The purpose of the current study was to evaluate short- and long-term effects of group reminiscence on agitated symptoms and quality of life (QOL) for individuals with dementia. A quasi-experimental study using a repeated-measures design was conducted in 43 residents with dementia. Participants received a 50-minute group reminiscence therapy session once per week for 10 weeks. Outcomes were measured 1 week before, 1 week after, and at 3 months postintervention. Results showed no significant difference on the overall agitated behavior of participants. However, verbally aggressive behavior decreased significantly ( p = 0.025), whereas intentional falling ( p = 0.025), hoarding ( p = 0.021), and akathisia ( p = 0.027) significantly decreased in the short term. Participation in group reminiscence therapy significantly improved QOL ( p < 0.001) across time periods for individuals with dementia. The findings provide information for professional and nonprofessional caregivers of individuals with specific agitated behaviors to improve their QOL. [ Journal of Psychosocial Nursing and Mental Health Services, 57 (8), 30–36.]

e12599 Background: Based on epithelial-mesenchymal transition (EMT) markers, circulating tumor cells (CTCs) can be classified into two main subtypes: epithelial CTCs(E-CTCs) and EMT-CTCs. CTCs with high expression of the FTH1 gene (HEF) may be related to poor efficacy of neoadjuvant chemotherapy (NAC). The relation between the CTCs with HEF and pathological complete response (pCR) after NAC is unclear. Methods: 83 non-metastatic breast cancer patients who completed NAC and surgery were enrolled in this study, and each patient had at least one result of CTC test before surgery. Expression of the FTH1 gene on CTCs was achieved by multiplex RNA in situ hybridization. Mann-Whitney U tests was conducted to examine the differences between the non-pCR and pCR groups in the numbers of total CTCs, E-CTCs and EMT-CTCs with HEF. Predictive ability of total and subtypes of CTCs with HEF to pCR rate was compared by the area under receiver operating characteristic curves (AUC). Univariate and multivariate binary logistic regression were used to select the variable and construct the predictive model. Results: Among 64 patients who underwent CTC test before NAC, CTCs were found in 52 patients, of which 20 patients achieved pCR. There was no significant difference in the numbers of total CTCs (9.9±10.9 vs 7.9±7.1, p=0.828) and E-CTCs with HEF (0.6±0.9 vs 0.3±0.7, p=0.256). Compared with the patients in the non-pCR group, those in pCR group had fewer EMT-CTCs with HEF (2.5±5.1 vs 1.0±2.5, p

e13015 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. However, the efficacy and safety data of eribulin for the ABC in Chinese patients is lacking, whether as first, second, or third-line regimens. This study aimed to evaluate the clinical effectiveness, safety, and treatment pattern of eribulin in first to third-line settings in Chinese ABC patients. Methods: Patients with histologically confirmed advanced breast cancer, who previously received ≤2 lines of treatment for metastatic disease were enrolled. In HR+/HER2- ABC, eribulin monotherapy was used; in HER2+ ABC, eribulin plus anti-HER2 targeted therapy were used; in metastasis triple-negative breast cancer (mTNBC), eribulin plus immunotherapy/chemotherapy were used. Primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: Forty-seven patients were enrolled from 2021.1.1 to 2021.10.20, including 41 metastatic and 6 de novo ABC patients. Eribulin was used as first-line therapy in 12 (25.5%) patients, second-line therapy in 24 patients (51.1%), and third-line therapy in 11 (23.1%) patients. More than 90% of the patients did not receive gemcitabine or vinorelbine, and 30.0% of them did not receive anthracycline or taxane previously. DCR was 70.2%, as 24 cases (51.1%) had stable disease and 9 cases (19.1%) had complete or partial remission. In subgroup analysis, median PFSs of 9.6 (95% CI: 6.5-12.7), 7.1 (95%CI: 4.4-9.8), and 5.6 (95%CI: 3.8-7.5) months were observed in patients receiving eribulin as first-, second-, and third-line therapy, respectively. In addition, median PFSs were 7.1 (95% CI: 5.1-9.3), 9.6 (95%CI: 3.6-15.7), 4.6 (95%CI: 4.6-4.6) and 5.8 (95%CI: 4.4-7.3) months for HR+/HER2-, HR+/HER2+, HR-/HER2+, and mTNBC patients, respectively. Other results from the subgroups analysis were shown in table. Common treatment-related toxicity was hematological toxicities including leukopenia (23%), neutropenia (17%), and thrombocytopenia (10%). There was no ≥grade 3 adverse events and no adverse event-related treatment discontinuation. Conclusions: Eribulin monotherapy or combined with targeted therapy was effective and well-tolerated as the first to third lines of treatment in ABC. This promising therapeutic outcome might warrant further studies in early eribulin administration in ABC patients. Clinical trial information: NCT04683445. [Table: see text]

TPS620 Background: As a latent new subtype, HER2-low-expressing breast cancer has attracted increasing attention. However, HER2-low-expressing/HR-positive early or locally advanced breast cancer (E/LABC) has the lowest pathological complete response (pCR) rate among all types of breast cancer. Pyrotinib, a small-molecule HER1/HER2/HER4 tyrosine kinase inhibitor, combined with chemotherapy regimen showed excellent efficacy and safety in the treatment of patients with HER2-positive early, locally advanced and metastatic breast cancer. In-vitro experiment showed pyrotinib can significantly inhibit colony formation in breast cancer cell lines with different HER2 expression levels including HER2-positive and HER2-low-expressimg [immunohistochemistry (IHC) 2+/in situ hybridization (ISH) negative]. Therefore, the investigator-driven, ongoing PILHLE-001 trial has been conducted to evaluate the potential role of neoadjuvant pyrotinib plus chemotherapy in the treatment of HER2-low-expressing/HR-positive E/LABC, which may provide a novel neoadjuvant therapeutic strategy for these patients. Methods: PILHLE-001, as a single-arm, phase Ⅱ study, is the first trial to evaluate the efficacy and safety of neoadjuvant pyrotinib combine with chemotherapy in HER2-low-expressing (defined as IHC 2+ with ISH negative) and HR-positive (ER or PR > 1% stained cells) E/LABC (cT1c with histologically involved lymph nodes or ≥cT2). Patients who have HER2 IHC 1+, or severe heart diseases or basic gastrointestinal diseases are excluded. The trial has 80% power to detect true difference from previous reported pCR rate of 17.5%, to an expected pCR rate of 35% at two-sided alpha level of 0.05. Considering a drop rate of 10%, a total of 46 patients will be needed. Since May 19, 2021 until now, 19 patients have been enrolled. All eligible patients will receive pyrotinib 320mg orally daily with all chemotherapy cycles (epirubicin 90 mg/m² intravenously plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by docetaxel 100 mg/m² intravenously on day 1 for four 3-week cycle). The primary outcome is the rate of total pCR, defined as no residual invasive tumor cells in the breast and axillary nodes, regardless of ductal carcinoma in situ (ypT0/is ypN0) after neoadjuvant treatment. The secondary outcomes include Miller-Payne grade, residual cancer burden score, overall response rate, breast conservation rate, disease-free survival, overall survival, exploratory biomarkers and drug related safety. Primary efficacy outcomes will be analyzed in the intention‐to‐treat population and safety outcomes in the safety set population. Long-term efficacy outcomes will be assessed later with enough follow-up. Clinical trial information: NCT05165225.

Hydrogen sulfide (H

Lithium-ion batteries with conventional LiPF6 carbonate electrolytes are prone to failure at high temperature. In this work, the thermal stability of a dual-salt electrolyte of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium difluoro(oxalato)borate (LiODFB) in carbonate solvents was analyzed by accelerated rate calorimetry (ARC) and differential scanning calorimetry (DSC). LiTFSI-LiODFB dual-salt carbonate electrolyte decomposed when the temperature exceeded 138.5 °C in the DSC test and decomposed at 271.0 °C in the ARC test. The former is the onset decomposition temperature of the solvents in the electrolyte, and the latter is the LiTFSI-LiODFB dual salts. Flynn-Wall-Ozawa, Starink, and autocatalytic models were applied to determine pyrolysis kinetic parameters. The average apparent activation energy of the dual-salt electrolyte was 53.25 kJ/mol. According to the various model fitting, the thermal decomposition process of the dual-salt electrolyte followed the autocatalytic model. The results showed that the LiTFSI-LiODFB dual-salt electrolyte is significantly better than the LiPF6 electrolyte in terms of thermal stability.

The physical origins of the transverse optical binding force and torque beyond the Rayleigh approximation have not been clearly expressed to date. Here, we present analytical expressions of the force and torque for a dual dipolar dielectric dimer illuminated by a plane wave propagating perpendicularly to the dimer axis. Using this analytical model, we explore the roles of the hybridized electric dipolar, magnetic dipolar, and electric-magnetic dipolar coupling interactions in the total force and torque on the particles. We find significant departures from the predictions of the Rayleigh approximation, particularly for high-refractive-index particles, where the force is dominated by the magnetic interaction. This results in an enhancement of the dimer stability by one to four orders of magnitude compared to the predictions of the Rayleigh approximation. For the case of torque, this is dominated by the coupling interaction and increases by an order of magnitude. Our results will help to guide future experimental work in optical binding of high-refractive-index dielectric particles., 14 pages, 10 figures

Autophagy is a catabolic process that removes aggregated proteins and damaged organelles via lysosomal degradation. Increasing evidence suggests that dysfunction of autophagy is associated with a variety of human pathologies, including aging, cancer, neurodegenerative diseases, heart diseases, diabetes, and other metabolic diseases. Current research suggests that the regulation of autophagy may be a novel target for the treatment of these diseases. For this purpose, it is essential to have a deep understanding on the molecular details of autophagy and its regulatory network in each of the disease contexts. Over the years, a variety of chemical autophagy inducers and inhibitors has been developed. The application of these autophagy regulators can assist us in the exploration of the mechanism and therapeutic potential of autophagy regulation. In this chapter, we summarize the recent advances in chemical autophagy regulators to provide methodological support for autophagy research.

Background Nurses often have difficulty to deal with dementia-related problematic behaviours, resulting in the prolonged hospitalisation of patients, which further waste medical resources and affect care quality, patient safety and nurses' job satisfaction. It is imperative to improve the dementia care competence of nurses working in acute care. Prior to educational interventions to promote dementia care, using an instrument to evaluate dementia care competence of nurses is needed. Purpose The purpose of this study was to develop and test the psychometric properties of a scale suitable for the investigation of dementia care competence of nurses working in acute care setting. Methods The instrumental development design adapted Iceberg Theory as the theoretical foundation was used to develop a scale through three stages: Item development, Content validity and Psychometric testing of the scale. Stratified random sampling was used to enrol subjects from two medical centres in southern Taiwan. The Content Validity Index (CVI), categorical principal components analysis (CATPCA), Cronbach's α coefficient test and the intra-class correlation coefficient test were used to analyse the data. Results This study enrolled a total of 308 subjects. The CVI of the entire scale reached .97. Through the CATPCA, resulting 33 items in total with the Knowledge subscale consists of 13 items (range = 0-13), the Attitude subscale consists of 11 items (range = 11-55) and the Skills subscale consists of 9 items (range = 0-9). The final Cronbach's alpha coefficient for the Knowledge subscale was .88; for the Attitude subscale was .94; and for the Skills subscale was .85. The test-retest reliability after 2 weeks reached .818. Conclusions/implications for practice This scale has good reliability, validity and theoretical support. It can be used to understand the current status and predicaments of dementia care faced by healthcare personnel working in acute care setting, as well as the educational training intervention required to be implemented. Hopefully, nurses' ability to deal with problematic behaviours of dementia can be improved.

Substantia nigra (SN) hyperechogenicity is present in most Parkinson’s disease (PD) cases but is occasionally absent in some. To date, age, gender, disease severity, and other factors have been reported to be associated with SN hyperechogenicity in PD. Previous studies have discovered that excess iron deposition in the SN underlies its hyperechogenicity in PD, which may also indicate the involvement of genes associated with iron metabolism in hyperechogenicity. The objective of our study is to explore the potential associations between variants in iron metabolism-associated genes and SN echogenicity in Han Chinese PD. Demographic profiles, clinical data, SN echogenicity and genotypes were obtained from 221 Han Chinese PD individuals with a sufficient bone window. Serum ferritin levels were quantified in 92 of these individuals by immunochemical assay. We then compared factors between PD individuals with SN hyperechogenicity and those with SN hypoechogenicity to identify factors that predispose to SN hyperechogenicity. Of our 221 participants, 122 (55.2%) displayed SN hyperechogenicity, and 99 (44.8%) displayed SN hypoechogenicity. Gender and serum ferritin levels were found to be associated with SN hyperechogenicity. In total, 14 genes were included in the sequencing part. After data processing, 34 common single nucleotide polymorphisms were included in our further analyses. In our data, we also found a significantly higher frequency of PANK2 rs3737084 (genotype: OR = 2.07, P = 0.013; allele: OR = 2.51, P = 0.002) in the SN hyperechogenic group and a higher frequency of PLA2G6 rs731821 (genotype: OR = 0.45, P = 0.016; allele: OR = 0.44, P = 0.011) in the SN hypoechogenic group. However, neither of the two variants was found to be correlated with serum ferritin. This study demonstrated that genetic factors, serum ferritin level, and gender may explain the interindividual variability in SN echogenicity in PD. This is an explorative study, and further replication is warranted in larger samples and different populations.

Introduction: The Saint Louis University Mental Status (SLUMS) examination is a common screening instrument to detect mild cognitive impairment (MCI) in Western countries. However, further work is needed to identify optimal SLUMS cutoff scores for screening MCI and dementia in Chinese populations. Objective: The aim of this study was to evaluate the utility and diagnostic accuracy of the SLUMS examination in the diagnosis of dementia and MCI in Chinese population. Methods: A cross-sectional multicenter design was conducted. Patients were recruited from the outpatient department of our neurology and psychiatric clinics. The establishment of the gold standard for the SLUMS-Chinese version (SLUMS-C) to detect MCI and dementia was based on the clinical criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) and related neuropsychological testing conducted by 3 certified dementia specialists. The consistency of the diagnosis process and administering SLUMS-C were established prior to the beginning of the study. Data were analyzed, and sensitivity, specificity, and areas under the curve (AUCs) were calculated. Results: A total of 367 subjects were recruited. The SLUMS-C did not show satisfactory AUCs for the preliminary detection of normal cognitive status and MCI by different educational levels (all AUC 0.32–0.54). However, the SLUMS-C showed acceptable AUCs for the preliminary detection of dementia by different educational levels (all AUC 0.78–0.81). An educational level of senior high school showed the best cutoff, sensitivity, and specificity. The SLUMS-C scores to detect dementia for individuals with at least high school education and less than high school education were Conclusions: Our results indicate that the SLUMS-C could be a beneficial and convenient screening instrument to detect dementia in Chinese population. After community screening, a comprehensive clinical evaluation including cognitive assessment, functional status, corroborative history, and imaging confirmation is needed.

Objective: To investigate the prevalence of family surrogates’ do-not-resuscitate (DNR) intention for patients with dementia (PwD), and factors influencing family surrogates’ decisions.Meth...

Objectives Pathogenic mutations in the glucocerebrosidase (GBA) gene are associated with Parkinson’s disease (PD), of which L444P and N370S are the most frequently observed in patients with PD. The aim of this study was to systematically explore variations in the coding regions of GBA in Han Chinese patients with PD, as well as to expand the GBA mutation spectrum. Material and methods A total of 213 Han Chinese patients with PD and 348 controls were enrolled in the study. Whole coding regions of GBA were captured and sequenced by target region sequencing. Sanger sequencing was also used to confirm the identified variants. Results We identified a novel variant (c. C646A; p.L216I; NM_001171811.1) of GBA in two unrelated patients, which was not observed in the controls. Both patients had early-onset PD and neither exhibited any motor-related symptoms. However, we did not find an L444P or N370S mutations in our patients. Conclusions The p.L216I mutation is a novel GBA mutation, which we identified in two Han Chinese patients with PD. The patients exhibited similar characteristics, which differed from those seen in patients with other GBA mutations. Future work is needed to investigate this mutation further, as well as larger cohort studies to explore other GBA mutations associated with PD in the Han Chinese and in other populations.

Background Dyskinesia is a troublesome complication of long-term dopaminergic medications in Parkinson's disease (PD) patients. Many factors are reported to be associated with dyskinesia in PD. Objective To investigate the association between sleep quality and dyskinesia in patients with PD. Methods Four hundred twenty-five patients with PD were enrolled in this study. Demographic information was collected. Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) stage scale were also performed. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were applied to evaluate daytime sleepiness and overall nighttime sleep quality, respectively, in PD patients. Results Patients with dyskinesia tended to have a longer duration of disease, higher daily levodopa-equivalent dose (LED), H-Y stage, UPDRS II and PSQI score, and a higher percentage of levodopa treatment than those without dyskinesia. After adjusting for age, sex, age at onset of PD, disease duration, UPDRS I, UPDRS II, UPDRS III, cigarette smoking, use of different antiparkinsonian drugs, phenotype, daily LED, and restless leg syndrome (RLS), PSQI score was still associated with dyskinesia, with corresponding ORs 1.111 (95% CI, 1.004–1.229) as a continuous variable, and 2.469 (95% CI, 1.051–5.800) as a categorical variable, respectively. Further analysis of PSQI components showed that subjective sleep quality and sleep latency were associated with dyskinesia in PD patients. Conclusions Our data showed that poor nighttime sleep is positively associated with dyskinesia in PD patients. Attention to the management of nighttime sleep quality may be beneficial to dyskinesia in patients with PD.

BACKGROUND Many optical coherence tomography (OCT) studies have reported alterations in the retinal nerve fiber layer (RNFL) in Parkinson's disease (PD) and other neurodegenerative diseases. However, whether retinal alterations are a biomarker for PD is still controversial. OBJECTIVE To investigate potential correlations between PD and morphological changes in retina using OCT and to determine its usefulness as a biomarker of disease progression in PD. METHODS We performed a cross-sectional study on patients with PD (N = 37) and age-matched controls (N = 42), followed by a longitudinal study of the PD patients (N = 22) over approximately 2.5 years. RESULTS The average retinal nerve fiber layer (RNFL) thickness (p

We present high-resolution, all-optical thermometry based on ensembles of germanium-vacancy (GeV) color center in diamond and implement this method of thermometry in the fiber-optic format. Due to the unique properties of diamond, an all-optical approach using this method opens a way to produce back-action-free temperature measurements with resolution below 0.1 K in a wide range of temperatures.