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Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.
This paper presents a low-profile miniaturized dual-band antenna utilizing the quarter-mode substrate integrated waveguide (QMSIW) structure. The two modes of TE110 and TE220 of a single QMSIW structure are employed, enabling a dual-band operation. The frequency ratio between the two bands can be tuned by loading a capacitive structure, which is comprised of a capacitive-loaded patch and a short circuit post, inside the QMSIW structure. By introducing parasitic QMSIW structures through magnetic coupling, a dual-band antenna with enhanced bandwidths is achieved. The antenna has dimensions of smaller than 400 mm2 (0.048λL2) with a uniform height of 1.4 mm (0.016λL). Measurement results indicate that the −6 dB impedance bandwidths of the antennas can cover the 5G N78 (3.3–3.6 GHz) and N79 (4.8–5 GHz) bands, and the average efficiencies is better than −2.5 dB. To the authors’ knowledge, the proposed designs offer dual-wideband operation while having the smallest planar dimension compared to the previously reported antennas. Furthermore, an extended electric coupling dual-band antenna configuration is also described and measured, which achieves similar bandwidth extension as the proposed antenna.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviours, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviours in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1’s analogues interact with alcohol-related behaviours may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.
Methods:
A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviours were assessed.
Results:
Preclinical studies (n = 19) indicate that GLP-1RAs attenuate alcohol-related behaviours, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (n = 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations.
Discussion:
Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioural modifications in individuals living with alcohol use disorder.
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroproliferative effects and modulatory effects in neuronal pathways. Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on neurogenesis.
Methods:
We examined studies that investigate changes in neurogenesis mediated by GLP-1 and GLP-1 RA administration in both human and animal populations. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to July 2nd. Primary studies investigating the role of GLP-1 and GLP-1 RAs on neurogenesis were included for analysis.
Results:
GLP-1 and GLP-1 RAs (i.e. exenatide, geniposide, liraglutide, lixisenatide, and semaglutide), increased neurogenesis within the dentate gyrus, hippocampus, olfactory bulb, and the medial striatum in animal models. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in multiple apoptotic pathways and upregulating survival pathways.
Discussion:
GLP-1 and GLP-1 RAs are positively associated with neurogenesis. This effect may have translational implications insofar as disparate mental disorders that are characterised by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.
Parkinson’s disease (PD) diagnosis mostly relies on (late) clinical (parkinsonism) symptoms, whereas we need early diagnostic markers in order to initiate and monitor the effects of forthcoming disease-modifying drugs in the earliest phase of this disease. Therefore, reliable diagnostic and prognostic biomarkers are urgently needed. Evidence suggests the potential (differential) diagnostic and prognostic value of clinical, genetic, neuroimaging, and biochemical markers (e.g., in saliva, urine, blood and cerebrospinal fluid). Such biomarkers may include α-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain, closely reflecting the pathophysiology of PD. Here, we provide an overview of these markers with practical guidelines for facilitating early PD diagnosis.
Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG.
Methods
Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria.
Results
We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis.
Conclusion
Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations.
The efficient separation of hexane isomers from the light naphtha fraction is a significant challenge in the petrochemical industry. 5A zeolite adsorbent is used commercially to sieve alkane isomers. In this study, 5A zeolites were synthesized using a low-cost natural clay mineral precursor, i.e. palygorskite (PAL), with the addition of crystallization directing agent (CDA). By varying the mass ratio of CDA/deionized water, 5A zeolites were obtained as CDA-5%, CDA-7.5%, and CDA-10%. All products were submicron particles with an average particle size of 400–800 nm. A sieving test of CDA-induced 5A zeolites was carried out on hexane adsorbates including n-hexane (nHEX), 2-methylpentane (2MP), and 3-methylpentane (3MP). According to vapor-phase batch adsorption experiments, a significant equilibrium amount (0.149 g/g) of nHEX and only 0.0321 g/g 2MP and 0.0416 g/g 3MP were adsorbed on the 5A zeolite product with CDA-5%. The dynamic adsorption performance of 5A zeolite (CDA-5%) was evaluated by breakthrough curves of binary mixtures of nHEX/2MP and nHEX/3MP. Palygorskite 5A (PAL 5A) zeolite achieved maximum dynamic adsorption capacities of nHEX (0.16 g/g in both cases) at 200°C and 1.2 MPa total pressure. This work provided an economic alternative for the synthesis of 5A zeolites using natural clay minerals instead of chemical raw materials.
Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear.
Methods
One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed.
Results
Cognitive impairment (global cognition, verbal memory, language, visual–spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS.
Conclusions
Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.
Depressive symptoms, functional impairment, and decreased quality of life (QOL) are three important domains of major depressive disorder (MDD). However, the possible causal relationship between these factors has yet to be elucidated. Moreover, it is not known whether certain symptoms of MDD are more impairing than others. The network approach is a promising solution to these shortfalls.
Methods
The baseline data of a multicenter prospective project conducted in 11 governances of China were analyzed. In total, 1385 patients with MDD were included. Depressive symptoms, functioning disability, and QOL were evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17), the Sheehan Disability Scale (SDS), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). The network was estimated through the graphical Least Absolute Shrinkage and Selection Operator (LASSO) technique in combination with the directed acyclic graph.
Results
Three centrality metrics of the graphical LASSO showed that social life dysfunction, QOL, and late insomnia exhibited the highest strength centrality. The network accuracy and stability were estimated to be robust and stable. The Bayesian network indicated that some depressive symptoms were directly associated with QOL, while other depressive symptoms showed an indirect association with QOL mediated by impaired function. Depressed mood was positioned at the highest level in the model and predicted the activation of functional impairment and anxiety.
Conclusions
Functional disability mediated the relationship between depressive symptoms and QOL. Family functionality and suicidal symptoms were directly related to QOL. Depressed mood played the predominant role in activating both anxiety symptom and functional impairment.
This paper aims to analyze the inequalities in general practitioner (GP) distribution in China.
Background:
GPs-based primary health care (PHC) has been implemented from 2011 in China, aiming to improve the accessibility and quality of basic medical and healthcare services. GPs in China, as the gatekeeper of people’s health, mainly undertake integrated health services at the grass-roots level.
Methods:
The number of GPs and inequality in GPs distribution from 2012 to 2018 was analyzed by the Lorenz Curve/Gini coefficient and Theil L index. Data were extracted from China Health Statistical Yearbook 2013–2019.
Findings:
The demographic Gini coefficient of GPs changed from 2012 (0.234) to 2018 (0.167), showing high equality in China. In contrast, the Thiel L index from 2012 (0.372) to 2018 (0.345) showed less equality. The decomposition of Thiel L index implicated the inequalities within the divisions. The number of GPs in China shows a fast growth trend since the general practice system established, and the GPs distribution becomes more demographically equitable. However, the shortage of GPs and inequality in their distribution remains severe. More incentive and supportive policies need to be made to enhance the quantity, quality, and structure of GPs in China.
Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.
Four of China’s six wintering populations of “grey” geese Anser spp. declined during the last decade. In contrast, the Bar-headed Goose A. indicus wintering population in China’s Tibet Autonomous Region more than doubled. During six surveys in Tibet over a 27-year period (1991/92 to 2017/18 winters) we documented an annual growth rate of 6.8% in the Bar-headed Goose population – an increase from approximately 10,100 to 68,100 birds. We propose that in addition to the cessation of hunting, the population growth of Bar-headed Goose is being driven by changes in agricultural land use patterns in Tibet, the establishment of protected areas on the wintering and breeding grounds, and the impacts of climate change across the Tibetan Plateau. Consistent with this hypothesis, the sown area of winter wheat in Tibet has increased and geese have shifted from primarily feeding in crop stubble to planted winter wheat fields. We also found that the most rapid population growth coincided with a 1998 climate regime shift across the Tibetan Plateau resulting in warmer temperatures, an increase in net precipitation, the appearance of new lakes and changes in the water levels and surface area of historical lakes. We suggest that warmer temperatures and high-quality forage on the south-central Tibet wintering grounds may be enhancing over-winter survival, while on the breeding grounds the expansion of lakes and wet meadows is augmenting breeding and brood-rearing habitat.
The aim of this study was to evaluate the management mode for the prevention and control of coronavirus disease 2019 (COVID-19) transmission used at a general hospital in Shenzhen, China, with the aim to maintain the normal operation of the hospital.
Methods:
From January 2, 2020, to April 23, 2020, Hong Kong–Shenzhen Hospital, a tertiary hospital in Shenzhen, has operated a special response protocol named comprehensive pandemic prevention and control model, which mainly includes 6 aspects: (1) human resource management; (2) equipment management; (3) logistics management; (4) cleaning, disinfection, and process reengineering; (5) environment layout; (6) and training and assessment. The detail of every aspect was described, and its efficiency was evaluated.
Results:
A total of 198,802 patients were received. Of those, 10,821 were hospitalized; 26,767 were received by the emergency department and fever clinics; 288 patients were admitted for observation with fever; and 324 were admitted as suspected cases for isolation. Under the protocol of comprehensive pandemic prevention and control model, no case of hospital-acquired infection with COVID-19 occurred among the inpatients or staff.
Conclusion:
The present comprehensive response model may be useful in large public health emergencies to ensure appropriate management and protect the health and life of individuals.
Few studies provide clear rationale for and the reception of adaptations of evidence-based interventions. To address this gap, we describe the context-dependent adaptations in critical time intervention-task shifting (CTI-TS), a manualized recovery program for individuals with psychosis in Rio de Janeiro, Brazil and Santiago, Chile. Implications of the adaptations – incorporating a task-shifting approach and modifying the mode of community-based service delivery – are examined from users' perspectives.
Methods
A secondary analysis of in-depth interviews with CTI-TS users (n = 9 in Brazil; n = 15 in Chile) was conducted. Using the framework method, we thematically compared how participants from each site perceived the main adapted components of CTI-TS.
Results
Users of both sites appreciated the task-shifting worker pair to provide personalized, flexible, and relatable support. They wanted CTI-TS to be longer and experienced difficulty maintaining intervention benefits in the long-term. In Chile, stigma and a perceived professional hierarchy toward the task-shifting providers were more profound than in Brazil. Engagement with community-based services delivery in homes and neighborhoods (Chile), and at community mental health centers (Brazil) were influenced by various personal, familial, financial, and social factors. Uniquely, community violence was a significant barrier to engagement in Brazil.
Conclusion
CTI-TS’ major adaptations were informed by the distinct mental health systems and social context of Santiago and Rio. Evaluation of user experiences with these adaptations provides insights into implementing and scaling-up task-shifting and community-oriented interventions in the region through the creation of specialized roles for the worker pair, targeting sustained intervention effects, and addressing socio-cultural barriers.
To explore the relationship between parameters of Na and K excretion using 24-h urine sample and mild cognitive impairment (MCI) in general population.
Design:
This is a cross-sectional study.
Setting:
Community-based general population in Emin China.
Participants:
Totally, 1147 subjects aged ≥18 years were selected to complete the study, with a multistage proportional random sampling method. Cognitive status was assessed with Mini Mental State Examination (MMSE) questionnaire and timed 24-h urine specimens were collected. Finally, 561 participants aged ≥35 years with complete urine sample and MMSE data were included for the current analysis and divided into groups by tertiles of 24-h urinary sodium to potassium ratio (24-h UNa/K) as lowest (T1), middle (T2) and highest (T3) groups.
Results:
The MMSE score was significantly lower in T3, compared with the T1 group (26·0 v. 25·0, P = 0·002), and the prevalent MCI was significantly higher in T3 than in T1 group (11·7 % v. 25·8 %, P < 0·001). In multiple linear regression, 24-UNa/K (β: −0·184, 95 % CI −0·319, −0·050, P = 0·007) was negatively associated with MMSE score. In multivariable logistic regression, compared with T1 group, 24-h UNa/K in the T2 and T3 groups showed 2·01 (95 % CI 1·03, 3·93, P = 0·041) and 3·38 (95 % CI 1·77, 6·44, P < 0·001) fold odds for presence of MCI, even after adjustment for confounders. More augmented results were demonstrated in sensitivity analysis by excluding individuals taking anti-hypertensive agents.
Conclusions:
Higher 24-h UNa/K is in an independent association with prevalent MCI.
Over the past few decades, the number of liquefied natural gas (LNG) ships and terminals has been increasing, playing an important role in global clean energy transportation. However, the traffic capacity of LNG shipping in port areas is limited because of its high safety requirements. In view of this problem, a novel model is proposed to study the ship traffic in a port area by combining cellular automaton (CA) and multi-agent methods. Taking the CNOOC Tianjin LNG Terminal as an example, the ship traffic in Tianjin Port is simulated. Based on the simulation results, the LNG ship traffic capacity and its impact on the general shipping traffic flow under different special traffic rules are obtained. This model can provide theoretical support for optimising the port traffic organisation for LNG ships.
Universities and public research institutes are encouraged to collaborate with industries and promote knowledge transfer from academia to the private sector in order to promote commercialization of inventions and to foster innovations that would facilitate economic growth. Patenting research outputs is one way of facilitating this knowledge transfer. This chapter focuses on tracking patenting as a way of measuring performance of public research organizations. The chapter proposes how patent filings across different countries using patent data filed through the Patent Cooperation Treaty can be captured and compared and how national-level patent data can be compiled using the PATSTAT database. The chapter shows that global patenting by public research institutions and universities has increased in the last thirty-five years, with patenting dominance shifting from Europe and the United States to Asia. It shows that while private sector businesses continue to play a major role in global patenting, public research organizations are emerging as important innovation drivers. The chapter concludes that while there are limitations in using patent data and the extent to which it measures innovativeness, these data are still useful in helping to identify potential weaknesses and highlight strengths of public research organizations.