Feasibility of wearable sensor signals and self-reported symptoms to prompt at-home testing for acute respiratory viruses in the USA (DETECT-AHEAD): a decentralised, randomised controlled trial.

BACKGROUND: Early identification of an acute respiratory infection is important for reducing transmission and enabling earlier therapeutic intervention. We aimed to prospectively evaluate the feasibility of home-based diagnostic self-testing of viral pathogens in individuals prompted to do so on the basis of self-reported symptoms or individual changes in physiological parameters detected via a wearable sensor. METHODS: DETECT-AHEAD was a prospective, decentralised, randomised controlled trial carried out in a subpopulation of an existing cohort (DETECT) of individuals enrolled in a digital-only observational study in the USA. Participants aged 18 years or older were randomly assigned (1:1:1) with a block randomisation scheme stratified by under-represented in biomedical research status. All participants were offered a wearable sensor (Fitbit Sense smartwatch). Participants in groups 1 and 2 received an at-home self-test kit (Alveo be.well) for two acute respiratory viral pathogens: SARS-CoV-2 and respiratory syncytial virus. Participants in group 1 could be alerted through the DETECT study app to take the at-home test on the basis of changes in their physiological data (as detected by our algorithm) or due to self-reported symptoms; those in group 2 were prompted via the app to self-test only due to symptoms. Group 3 served as the control group, without alerts or home testing capability. The primary endpoints, assessed on an intention-to-treat basis, were the number of acute respiratory infections presented (self-reported) and diagnosed (electronic health record), and the number of participants using at-home testing in groups 1 and 2. This trial is registered with ClinicalTrials.gov, NCT04336020. FINDINGS: Between Sept 28 and Dec 30, 2021, 450 participants were recruited and randomly assigned to group 1 (n=149), group 2 (n=151), or group 3 (n=150). 179 (40%) participants were male, 264 (59%) were female, and seven (2%) identified as other. 232 (52%) were from populations historically under-represented in biomedical research. 118 (39%) of the 300 participants in groups 1 and 2 were prompted to self-test, with 61 (52%) successfully completing self-testing. Participants were prompted to home-test more frequently due to symptoms (41 [28%] in group 1 and 51 [34%] in group 2) than due to detected physiological changes (26 [17%] in group 1). Significantly more participants in group 1 received alerts to test than did those in group 2 (67 [45%] vs 51 [34%]; p=0·047). Of the 61 individuals who were prompted to test and successfully did so, 19 (31%) tested positive for a viral pathogen-all for SARS-CoV-2. The individuals diagnosed as positive for SARS-CoV-2 in the electronic health record were eight (5%) in group 1, four (3%) in group 2, and two (1%) in group 3, but it was difficult to confirm if they were tied to symptomatic episodes documented in the trial. There were no adverse events. INTERPRETATION: In this direct-to-participant trial, we showed early feasibility of a decentralised programme to prompt individuals to use a viral pathogen diagnostic test based on symptoms tracked in the study app or physiological changes detected using a wearable sensor. Barriers to adequate participation and performance were also identified, which would need to be addressed before large-scale implementation. FUNDING: Janssen Pharmaceuticals.

Engagement with health research summaries via digital communication to All of Us participants.

OBJECTIVE: Summaries of health research can be a complementary way to return value to participants. We assess how research participants engage with summaries via email communication and how this can be improved. MATERIALS AND METHODS: We look at correlations between demographic subgroups and engagement in a longitudinal dataset of 305 626 participants (77% are classified as underrepresented in biomedical research) from the All of Us Research Program. We compare this against engagement with other program communications and use impact evaluations (N = 421 510) to measure the effect of tailoring communication by (1) eliciting content preferences, (2) Spanish focused content, (3) informational videos, and (4) article content in the email subject line. RESULTS: Between March 2020 and October 2021, research summaries reached 67% of enrolled participants, outperforming other program communication (60%) and return of results (31%), which have a high uptake rate but have been extended to a subset of eligible participants. While all demographic subgroups engage with research summaries, participants with higher income, educational attainment, White, and older than 45 years open and click content most often. Surfacing article content in the email subject line and Spanish focused content had negative effects on engagement. Video and social media content and eliciting preferences led to a small directional increase in clicks. DISCUSSION: Further individualization of tailoring efforts may be needed to drive larger engagement effects (eg, delivering multiple articles in line with stated preferences, expanding preference options). Our findings are likely a conservative representation of engagement effects, given the coarseness of our click rate measure. CONCLUSIONS: Health research summaries show promise as a way to return value to research participants, especially if individual-level results cannot be returned. Personalization of communication requires testing to determine whether efforts are having the expected effect.

BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in MI/R induced myocyte apoptosis.

BACKGROUND: Cardiomyocyte apoptosis plays a vital role in myocardial ischemia-reperfusion (MI/R) injury; however, the role of beclin1 (BECN1) remains unclear. This study aimed at revealing the function of BECN1 during cardiomyocyte apoptosis after MI/R injury. METHODS: In vivo, TTC and Evan's blue double staining was applied to verify the gross morphological alteration in both wild type (WT) mice and BECN1 transgene mice (BECN1-TG), and TUNEL staining and western blot were adopted to evaluate the cardiomyocyte apoptosis. In vitro, a hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate MI/R injury. Proteomics analysis was preformed to verify if apoptosis occurs in the H/R cellular model. And apoptosis factors, RIPK1, Caspase-1, Caspase-3, and cleaved Caspase-3, were investigated using western bolting. In addition, the mRNA level were verified using RT-PCR. To further investigate the protein interactions small interfering RNA and lentiviral transfection were used. To continue investigate the protein interactions, immunofluorescence and coimmunoprecipitation were applied. RESULTS: Morphologically, BECN1 significantly attenuated the apoptosis from TTC-Evan's staining, TUNEL, and cardiac tissue western blot. After H/R, a RIPK1-induced complex (complex II) containing RIPK1, Caspase-8, and FADD was formed. Thereafter, cleaved Caspase-3 was activated, and myocyte apoptosis occurred. However, BECN1 decreased the expression of RIPK1, Caspase-8, and FADD. Nevertheless, BECN1 overexpression increased RIPK1 ubiquitination before apoptosis by inhibiting OTUD1. CONCLUSIONS: BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in C-Caspase-3-induced myocyte apoptosis after MI/R injury. Therefore, BECN1 can function as a cardioprotective candidate.

Risk Factors for Cancer Malnutrition after Radical Tumor Resection.

Objective: To investigate the risk factors for cancer malnutrition after radical tumor resection. Methods: A total of 110 cancer patients who used parenteral nutrition from January 2022 to June 2023 were selected for retrospective analysis and 50 patients who did not need parenteral nutrition support after radical tumor resection were selected as the control group to analyze the general data of the two groups. Univariate and multivariate logistic analyses were used to determine the factors influencing malnutrition in patients supported by parenteral nutrition after radical tumor resection. Results: The age(P = .032), body mass index(P = .012), education level(P = .025), per capita monthly household income(P = .029), concurrent chemotherapy ratio(P = .035), phobia disease progression(P = .037), and depression(P = .038) of patients who underwent parenteral nutrition after radical tumor resection were all influencing factors, and the differences were statistically significant (P < .034). After undergoing a radical tumor resection, patients with dysphagia grade 2-3, loss of appetite grade 2-3, and nausea and vomiting grade 2-3, as well as diarrhea grade 2-3, require parenteral nutrition support. The risk factors for malnutrition in patients who require such support include age, education, per capita household income, fear of disease progression, depression, pain, and diarrhea. Conclusion: Patients may suffer from malnutrition after radical tumor resection and need parenteral nutrition support, including age, education level, per capita monthly household income, fear of disease progression, depression, pain, diarrhea, etc., so in clinical nursing, nursing staff should pay more attention to such high-risk factors, so as to carry out personalized nursing programs for patients undergoing radical tumor resection and improve the effectiveness of disease treatment.

Unilateral Abduction Dorsiflexion Mechanism Brace as an Attractive Alternative of Congenital Talipes Equino-Varus Treatment - a Preliminary Report.

Ponseti method of CTEV treatment includes use of a foot orthosis, compliance with this can be a challenge. A new brace- Abduction Dorsiflexion Mechanism brace (ADM, C-Prodirect) was introduced to address this. The aim of the study was to assess whether the new ADM brace improves compliance and prevents relapse in children with corrected clubfoot. Eight children with unilateral CTEV who did not tolerate the standard brace were included in the study. All children had been previously treated with Ponseti casting, Achilles tenotomy and Ponseti AFO Abduction Brace (C-Prodirect®). The mean age of children included was 27 months. Parents' satisfaction with the brace was assessed using Client Satisfaction with Device (CSD) questionnaire. Parents reported better tolerance of the brace by the child in six out of eight cases. ADM brace is viable alternative in maintaining correction of unilateral idiopathic CTEV when compliance to standard AFO abduction brace is poorly tolerated.

Knowledge, attitude, behaviour, and influencing factors of home-based medication safety among community-dwelling older adults with chronic diseases: a cross-sectional study.

BACKGROUND: Older adults with chronic diseases require long-term medication. However, due to lack of drug knowledge and hypomnesia, older adults with chronic diseases are prone to adverse drug events and increased medical costs. This study aimed to explore the status and influencing factors of home-based medication safety among community-dwelling older adults with chronic diseases in China to provide a basis for follow-up to conduct targeted health education. METHODS: Overall, 427 community-dwelling older adults with chronic diseases participated in this study. The Knowledge, Attitude, and Behaviour of Medication Safety among Older Adults with Chronic Diseases Questionnaire was used to assess their home-based medication safety. Multivariate linear regression was used to identify the factors influencing knowledge, attitude, and behaviour regarding medication safety. RESULTS: The average score of home-based medication safety among older adults with chronic diseases was 68.26 ± 8.96, indicating that they had a moderate grasp of medication safety. The scoring rate of each subscale was ranked from high to low as follows: behaviour (84.51%), knowledge (63.33%), and attitude (47.39%). Stepwise linear regression analysis showed that medication safety knowledge, attitudes, and behaviours were significantly associated with higher monthly income, adverse drug events, and taking medicine several times a day (p < 0.05). Additional influencing factors included having fewer chronic diseases, being female, higher educational attainment, taking medicines multiple kinds a day, better self-care ability, and non-hospitalisation for chronic illnesses (p < 0.05). CONCLUSION: Medical staff and community workers should pay attention to the drug safety of older adults with different characteristics and mobilise their enthusiasm for participation to improve their medication self-management ability. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR2200060987 ; reg. date: 15/06/2022.

Synergistic effects of lipopolysaccharide and rotenone on dopamine neuronal damage in rats.

INTRODUCTION: The etiology of Parkinson's disease (PD) is still unknown. Until now, oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. However, the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear. METHODS: The changes in motor behavior, dopamine (DA) neurons quantification and their mitochondrial respiratory chain, glial cells activation and secreted cytokines, Nrf2 signaling pathway, and redox balance in the brain of rats were evaluated. RESULTS: Lipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, DA neuron damage, activation of glial cells, and release of related mediators, activation of Nrf2 signaling and destruction of oxidative balance. In addition, further studies indicated that after ROT-induced oxidative stress caused direct damage to DA neurons, LPS-induced inflammatory effects had stronger promoting neurotoxic effects on the above aspects. CONCLUSIONS: Neuroinflammation and oxidative stress synergistically aggravated DA neuronal loss. Furtherly, oxidative stress followed by neuroinflammation caused more DA neuronal loss than neuroinflammation followed by oxidative stress.

The association of air pollutants with hospital outpatient visits for child and adolescence psychiatry in Shenzhen, China.

BACKGROUND: Although exposure to ambient air pollution has been associated with mental disorder, little is known about its potential effects on children and adolescents, especially in Chinese population. We aimed to reveal the relationship of air pollutants with hospital outpatient visits for child and adolescence psychiatry (HOVCAP) in Shenzhen. METHODS: A case-crossover study based on time-series data was applied, and a distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of 4 major air pollutants (NO2, PM2.5, SO2 and O3) on HOVCAP. Least absolute shrinkage and selection operator (LASSO) regression was used to control the multicollinearity between covariates and to filter variables. RESULT: A total of 94,660 cases aged 3-18 were collected from 2014 to 2019 in the Mental Health Center of Shenzhen. Results of pollutants at mode value (M0) showed that in the single lag effect result, when the average daily concentration of NO2 at 24 µg/m3, there was a significant effect on HOVCAP over lag 1, lag 4 and lag 5, respectively. The cumulative RR of NO2 M0 value to the outpatient visits were 1.438 (1.137-1.818) over lag 0-2, 1.454 (1.120-1.887) over lag 0-3, 1.466 (1.084-1.982) over lag 0-4, 1.680 (1.199-2.354) over lag 0-5, 1.993 (1.369-2.903) over lag 0-6, and 2.069 (1.372-3.119) over lag 0-7. However, PM2.5, SO2, O3 were not associated with HOVCAP over neither single lag effects nor cumulative effects. The RR values both shown an increase either when NO2 increases by 10 units or when the maximum concentration of NO2 is reached. CONCLUSION: Our study suggests that exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. However, PM2.5, SO2, O3 were not associated with HOVCAP.

Relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China: a structural equation modeling.

BACKGROUND: Aging and empty-nesting in China are becoming more and more serious. Empty-nesters refer to older adults who were not living with their children, were living alone, or were living independently with their spouses. The mental health of empty-nesters needs timely attention. Satisfying the needs of older adults is primarily dependent on their children. Therefore, this study aimed to explore relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China. METHODS: This study employs the Children-related Factors Questionnaire (CFQ), the Chinese Version of the Basic Psychological Need Satisfaction (BPNS) Scale, and the Multiple Happiness Questionnaire (MHQ) to explore children-related factors, basic psychological need satisfaction and multiple happiness of urban empty-nesters in Fuzhou, China. A total of 507 samples were recruited by cluster sampling. RESULTS: Factors that affect BPNS include physical condition, the number of children, satisfaction with children's marriage, employment and income, retirement, gender, monthly personal income, and self-care have statistical differences (P < 0.05). Factors that affect MHQ include physical condition, the number of children, satisfaction with children's marriage, employment and income, gender, monthly personal income, living status, and self-care have statistical significances (P < 0.05). Structural equation model results showed that BPNS directly impacted MHQ, and factors about children indirectly affect MHQ through BPNS. The mediating role of BPNS in the relationship between children-related factors and MHQ. CONCLUSION: We should encourage our children to spend more time with the empty-nesters and communicate with them, which could help them relieve their negative emotions, satisfy their psychological needs, and improve their well-being. TRIAL REGISTRATION: Reg date: 20/08/2021; No. ChiCTR2100050175.

Exploring urban empty-nesters' using WeChat influencing factors and quality of life: A qualitative descriptive study.

OBJECTIVE: To explore urban empty-nesters using WeChat influencing factors and experiences of improving their quality of life. METHODS: 14 registered empty-nesters who had used WeChat in Fuzhou communities were recruited via convenience and purposive sampling methods with a qualitative descriptive design. Data were collected through individual, semi-structured, and face-to-face interviews and analyzed according to content analysis. RESULTS: The research revealed two primary themes with associated sub-themes: 1) influencing factors of using WeChat, and 2) quality of life experiences. DISCUSSIONS: Physiological factors, education level, and social support were using WeChat influencing factors by urban empty-nesters. WeChat is a convenient channel to improve empty-nesters' daily lives and a practical platform to meet empty-nesters' needs. Identifying these experiences could help older adults, especially empty-nesters' accept the era of intelligence and provide inspiration and reference for the increasingly normalized empty nest life.

Diagnosis of fetal total anomalous pulmonary venous connection based on the post-left atrium space ratio using artificial intelligence.

OBJECTIVE: To explore whether the post-left atrium space (PLAS) ratio would be useful for prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) using echocardiography and artificial intelligence. METHODS: We retrospectively included 642 frames of four-chamber views from 319 fetuses (32 with TAPVC and 287 without TAPVC) in end-systolic and end-diastolic periods with multiple apex directions. The average gestational age was 25.6 ± 2.7 weeks. No other cardiac or extracardiac malformations were observed. The dataset was divided into a training set (n = 540; 48 with TAPVC and 492 without TAPVC) and test set (n = 102; 20 with TAPVC and 82 without TAPVC). The PLAS ratio was defined as the ratio of the epicardium-descending aortic distance to the center of the heart-descending aortic distance. Supervised learning was used in DeepLabv3+, FastFCN, PSPNet, and DenseASPP segmentation models. The area under the curve (AUC) was used on the test set. RESULTS: Expert annotations showed that this ratio was not related to the period or apex direction. It was higher in the TAPVC group than in the control group detected by the expert and the four models. The AUC of expert annotations, DeepLabv3+, FastFCN, PSPNet, and DenseASPP were 0.977, 0.941, 0.925, 0.856, and 0.887, respectively. CONCLUSION: Segmentation models achieve good diagnostic accuracy for TAPVC based on the PLAS ratio.

Effects of intraperitoneal injection of lipopolysaccharide-induced peripheral inflammation on dopamine neuron damage in rat midbrain.

INTRODUCTION: Current studies have documented neuroinflammation is implicated in Parkinson's disease. Recently, growing evidence indicated peripheral inflammation plays an important role in regulation of neuroinflammation and thus conferring protection against dopamine (DA) neuronal damage. However, the underlying mechanisms are not clearly illuminated. METHODS: The effects of intraperitoneal injection of LPS (LPS[i.p.] )-induced peripheral inflammation on substantia nigra (SN) injection of LPS (LPS[SN] )-elicited DA neuronal damage in rat midbrain were investigated. Rats were intraperitoneally injected with LPS (0.5 mg/kg) daily for 4 consecutive days and then given single injection of LPS (8 µg) into SN with an interval of 0 (LPS(i.p.) 0 day ± LPS(SN) ), 30 (LPS(i.p.) 30 days ± LPS(SN) ), and 90 (LPS(i.p.) 90 days ± LPS(SN) ) days after LPS(i.p.) administration. RESULTS: LPS(i.p.) increased the levels of inflammatory factors in peripheral blood in (LPS(i.p.) 0 day ± LPS(SN) ). Importantly, in (LPS(i.p.) 0 day ± LPS(SN) ) and (LPS(i.p.) 30 days ± LPS(SN) ), LPS(i.p.) attenuated LPS(SN) -induced DA neuronal loss in SN. Besides, LPS(i.p.) reduced LPS(SN) -induced microglia and astrocytes activation in SN. Furtherly, LPS(i.p.) reduced pro-inflammatory M1 microglia markers mRNA levels and increased anti-inflammatory M2 microglia markers mRNA levels. In addition, the increased T-cell marker expression and the decreased M1 microglia marker expression and more DA neuronal survival were discerned at the same area of rat midbrain in LPS(SN) -induced DA neuronal damage 30 days after LPS(i.p.) application. CONCLUSION: This study suggested LPS(i.p.) -induced peripheral inflammation might cause T cells to infiltrate the brain to regulate microglia-mediated neuroinflammation, thereby protecting DA neurons.

Piperine Provides Neuroprotection against Kainic Acid-Induced Neurotoxicity via Maintaining NGF Signalling Pathway.

The neuroprotective properties of piperine, the major alkaloid extracted from black pepper, have been under investigation, but its mechanism of action in excitotoxicity is still poorly understood. This study aimed to evaluate the protective effects of piperine with a focus on nerve growth factor (NGF) signalling in a kainic acid (KA) rat model of excitotoxicity. Rats were administered intraperitoneally (i.p.) piperine (10 or 50 mg/kg) before KA injection (15 mg/kg, i.p.). Our results show that KA exposure in rats caused seizure behaviour, intrinsic neuronal hyperactivity, glutamate elevation, hippocampal neuronal damage, and cognitive impairment. These KA-induced alterations could be restored to the normal state by piperine treatment. In addition, piperine decreased the expression of the NGF precursor proNGF and NGF-degrading protease matrix metalloproteinase 9, whereas it increased the expression of proNGF processing enzyme matrix metalloproteinase 7, NGF, and NGF-activated receptor TrkA in the hippocampus of KA-treated rats. Furthermore, KA decreased phosphorylation of the protein kinase B (Akt) and glycogen synthase kinase 3ß (GSK3ß) in the hippocampus, and piperine reversed these changes. Our data suggest that piperine protects hippocampal neurons against KA-induced excitotoxicity by upregulating the NGF/TrkA/Akt/GSK3ß signalling pathways.

Corrigendum: An Ethnobotanical Study of Medicinal Plants in Kinmen.

[This corrects the article DOI: 10.3389/fphar.2021.681190.].

FLAIR vessel hyperintensities predict functional outcomes in patients with acute ischemic stroke treated with medical therapy.

OBJECTIVES: The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy. METHODS: Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale > 2 at 3 months. RESULTS: Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p < 0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p < 0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p < 0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes. CONCLUSION: FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy. KEY POINTS: • FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. • FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. • The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.

Ethnobotanical Survey on Bitter Tea in Taiwan.

Ethnopharmacological evidence: In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze. Bitter tea (kǔ-chá), a series of herbal teas prepared in response to common diseases in Taiwan, is often made from local Taiwanese plants. However, the raw materials and formulations have been kept secret and verbally passed down by store owners across generations without a fixed recipe, and the constituent plant materials have not been disclosed. Aim of the study: The aim was to determine the herbal composition of bitter tea sold in Taiwan, which can facilitate further studies on pharmacological applications and conserve cultural resources. Materials and methods: Interviews were conducted through a semi-structured questionnaire. The surveyed respondents were traditional sellers of traditional herbal tea. The relevant literature was collated for a systematic analysis of the composition, characteristics, and traditional and modern applications of the plant materials used in bitter tea. We also conducted an association analysis of the composition of Taiwanese bitter tea with green herb tea (qing-cao-cha tea), another commonly consumed herbal tea in Taiwan, as well as herbal teas in neighboring areas outside Taiwan. Results: After visiting a total of 59 stores, we identified 32 bitter tea formulations and 73 plant materials. Asteraceae was the most commonly used family, and most stores used whole plants. According to a network analysis of nine plant materials used in high frequency as drug pairs, Tithonia diversifolia and Ajuga nipponensis were found to be the core plant materials used in Taiwanese bitter tea. Conclusion: Plant materials used in Taiwanese bitter tea were distinct, with multiple therapeutic functions. Further research is required to clarify their efficacy and mechanisms.

Kaempferol 3-Rhamnoside on Glutamate Release from Rat Cerebrocortical Nerve Terminals Involves P/Q-Type Ca2+ Channel and Ca2+/Calmodulin-Dependent Protein Kinase II-Dependent Pathway Suppression.

Excess synaptic glutamate release has pathological consequences, and the inhibition of glutamate release is crucial for neuroprotection. Kaempferol 3-rhamnoside (KR) is a flavonoid isolated from Schima superba with neuroprotective properties, and its effecton the release of glutamate from rat cerebrocortical nerve terminals was investigated. KR produced a concentration-dependent inhibition of 4-aminopyridine (4-AP)-evoked glutamate release with half-maximal inhibitory concentration value of 17 µM. The inhibition of glutamate release by KR was completely abolished by the omission of external Ca2+ or the depletion of glutamate in synaptic vesicles, and it was unaffected by blocking carrier-mediated release. In addition, KR reduced the 4-AP-evoked increase in Ca2+ concentration, while it did not affect 4-AP-evoked membrane potential depolarization. The application of selective antagonists of voltage-dependent Ca2+ channels revealed that the KR-mediated inhibition of glutamate release involved the suppression of P/Q-type Ca2+ channel activity. Furthermore, the inhibition of release was abolished by the calmodulin antagonist, W7, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN62, but not by the protein kinase A (PKA) inhibitor, H89, or the protein kinase C (PKC) inhibitor, GF109203X. We also found that KR reduced the 4-AP-induced increase in phosphorylation of CaMKII and its substrate synapsin I. Thus, the effect of KR on evoked glutamate release is likely linked to a decrease in P/Q-type Ca2+ channel activity, as well as to the consequent reduction in the CaMKII/synapsin I pathway.

Soybean Meal Extract Preserves Memory Ability by Increasing Presynaptic Function and Modulating Gut Microbiota in Rats.

Age-related degenerative brain diseases frequently manifest as memory deficits. Dietary interventions or nutraceuticals may provide efficacious treatments through prevention and cure. Soybean meal, a byproduct of soy oil refining, has health benefits, but its effect on memory function is unknown. Therefore, we evaluated the effect of the oral administration of soybean meal extract (SME) for 2 weeks on memory function using the Morris water maze (MWM) test in healthy rats and investigated the possible underlying mechanisms. First, analysis of the composition revealed that SME is rich in isoflavones; SME did not exhibit hepatotoxicity or renal toxicity at the different doses tested. The MWM results revealed that the escape latency and movement distance of rats were significantly shorter in the SME group than in the control group, indicating that SME can help in memory preservation. In addition, SME increased the levels of presynaptic proteins such as synaptophysin, synaptobrevin, synaptotagmin, syntaxin, synapsin I, and 25-kDa synaptosome-associated protein as well as protein kinases and their phosphorylated expression, including extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase C (PKC), and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal nerve terminals (synaptosomes). Transmission electron microscopy also indicated that SME increased the number of synaptic vesicles in hippocampal synaptosomes. Furthermore, SME rats exhibited altered microbiota composition compared with control rats. Therefore, our data suggest that SME can increase presynaptic function and modulate gut microbiota, thus aiding in memory preservation in rats.

Non-conventional superconductivity in magnetic In and Sn nanoparticles.

We report on experimental evidence of non-conversional pairing in In and Sn nanoparticle assemblies. Spontaneous magnetizations are observed, through extremely weak-field magnetization and neutron-diffraction measurements, to develop when the nanoparticles enter the superconducting state. The superconducting transition temperature TC shifts to a noticeably higher temperature when an external magnetic field or magnetic Ni nanoparticles are introduced into the vicinity of the superconducting In or Sn nanoparticles. There is a critical magnetic field and a critical Ni composition that must be reached before the magnetic environment will suppress the superconductivity. The observations may be understood when assuming development of spin-parallel superconducting pairs on the surfaces and spin-antiparallel superconducting pairs in the core of the nanoparticles.

Severity of Intracranial Large Artery Disease Correlates With Cerebral Small Vessel Disease.

BACKGROUND: Small vessel disease (SVD) shares common vascular risk factors with large artery disease (LAD). However, little is known about the relationship between intracranial artery stenosis and SVD burden. PURPOSE: To investigate whether SVD burden correlates with severity of intracranial LAD. STUDY TYPE: Retrospective. POPULATION: Five hundred and sixteen patients with LAD of arterial circulation were enrolled from one hospital, including 384 males (59 ± 11 years) and 132 females (60 ± 12 years). FIELD STRENGTH/SEQUENCE: 3 T. T1 -weighted fast spin echo (T1 W FSE), T2 W FSE, T2 fluid attenuated inversion recovery, diffusion-weighted imaging, susceptibility-weight imaging, and time-of-flight magnetic resonance angiography. ASSESSMENT: The LAD was divided into mild stenosis (<30%), moderate stenosis (30%-69%), and severe stenosis (≥70%). The Standard for Reporting Vascular Changes on Neuroimaging criteria was used to rate the SVD burden according to the level of white matter hyperintensity (WMH), perivascular space (PVS), cerebral microbleed (CMB), and lacunes. STATISTICAL TESTS: Lilliefors test, ANOVA, chi-squared test, Mann-Whitney U test, Wilcoxon signed rank test, Bonferroni test, Spearman's correlation, logistic regression, and Cohen's kappa test. RESULTS: The grade scores for centrum semiovale PVS (CS-PVS) were positively correlated with the degree of stenosis (R = 0.413), whereas the presence of severe basal ganglia PVS (BG-PVS) was associated with CMB (R = 0.508), lacunes (R = 0.365), and severe WMH (R = 0.478). In multivariate analysis, severe CS-PVS (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.9-4.8) and lacunes (aOR, 2.1; 95% CI, 1.3-3.4) were associated with severe stenosis of LAD. In addition, CS-PVS was related to severe stenosis in a dose-dependent manner: when CS-PVS score was 3 and 4, the aORs of severe stenosis were 1.9 and 7.7, respectively. DATA CONCLUSION: The severity of LAD in anterior circulation is associated with SVD burden, which suggests that different SVD burden may be used for risk stratification in LAD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.