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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.
Successful development of technologies to support older people in care homes remains challenging. The strategic establishment of a group of residential settings providing 24-7 living labs plus an innovation hub is described. Acoustic monitoring (AM) for continuous nighttime checking of residents was selected for assessment. A pilot study in 2016 identified potential cost savings, reduced nighttime falls, and improved daytime well-being.
Methods
The AM system was systematically assessed in four WCS Care Group Ltd care homes following demonstration and testing in an innovation hub. The first author undertook a mixed-methods study (2019 to 2023) to assess the technology in terms of falls prevention, practical implementation, and future benefits of enhanced sound classification using artificial intelligence (AI). In 2020, a network of care providers, the National Care Forum (NCF), was funded by National Health Service Digital to develop three similar innovation hubs across England. The NCF undertook a national survey to identify priorities in terms of implementing new technologies in care homes.
Results
Structured interviews with care workers and observational assessment in four care homes confirmed that the AM system has the potential to identify active residents and reduce the risk of falls, although it cannot offer fall prediction or prevention functionality. Two new functions were proposed. Eight machine learning models for sound classification and demonstration tests in three simulated settings supported feasibility and adoption. A post-demonstration survey (n=39) identified a high probability of adoption for these additional functions. The NCF survey found that the top four new technologies of interest to care homes were medication management systems, electronic care planning, wearable GPS trackers, and AM systems.
Conclusions
Care homes report interest in procuring AM systems, which could reduce the risk of falls. In addition, new AI-supported functions are acceptable to care providers. The UK government has proposed that 20 percent of care homes introduce AM by March 2024. Guidelines for future assessment of sustainable care technologies in living lab settings now need to be developed.
This study aimed to assess the relationship between COVID-19 infection-related conditions and depressive symptoms among medical staff after easing the zero-COVID policy in China, and to further examine the mediating role of professional burnout.
Methods
A total of 1716 medical staff from all levels of health care institutions in 16 administrative districts of Beijing, China, were recruited to participate at the end of 2022 in this cross-sectional study. Several multiple linear regressions and mediating effects tests were performed to analyze the data.
Results
At the beginning of the end of the zero-COVID policy in China, 91.84% of respondents reported infection with COVID-19. After adjusting for potential confounding variables, the severity of infection symptoms was significantly positively associated with high levels of depressive symptoms (β = 0.06, P < 0.001), and this association was partially mediated by professional burnout. Specifically, emotional exhaustion (95% CI, 0.131, 0.251) and depersonalization (95% CI, 0.009, 0.043) significantly mediated the association between the severity of infection symptoms and depressive symptoms.
Conclusions
The mental health of medical staff with more severe symptoms of COVID-19 infection should be closely monitored. Also, interventions aimed at reducing emotional exhaustion and depersonalization may effectively reduce their risk of developing depressive symptoms.
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.
Gentiana straminea Maxim. (Gentianaceae) is an important traditional Tibetan herb that is mainly distributed on the Qinghai-Tibetan Plateau. Despite its agricultural and pharmacological importance, there remains a paucity of microsatellite markers, particularly expressed sequence tag-simple sequence repeat (EST-SSR) markers, available for this local endemic species. In this study, based on previous Illumina transcriptome data of G. straminea, a total of 96 EST-SSR markers were initially designed and tested. Thirty-two of 96 loci (33.33%) were successfully amplified and verified for validation. Among them, 10 were polymorphic and had clear bands. The polymorphism information content values were 0.09–0.799, the number of alleles per locus ranged from 3 to 14, and the levels of observed and expected heterozygosity were 0.078–0.722 and 0.238–0.884, respectively, which suggested a high level of information. Moreover, cross-amplification was successful for 10 loci in two other related species, Gentiana macrophylla Pallas and Gentiana dahurica Fischer. These EST-SSR markers provide a valuable tool for investigating the genetic diversity related to quantitative traits and population genetic studies on G. straminea and related species in sect. Cruciata Gaudin.
Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children’s Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1–4 years exhibited higher risk of PTB and TB meningitis, and children aged 5–12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.
To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers.
Methods
This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up.
Results
Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = −1.23, 95% CI = −2.36, −0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = −0.89, 95% CI = −1.50, −0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness.
Conclusions
This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.
Creating an environmentally friendly precursor to form a kaolinite intercalation compound is important for promoting the applications of nanohybrid kaolinite in electrochemical sensors, low- or zero-toxicity drug carriers, and clay-polymer nanocompounds. In the present study, a stable hydrated kaolinite pre-cursor with d001= 0.84 nm was prepared successfully by heating the transition phase, the as-prepared kaolinite-hydrazine intercalate, at temperatures between 40 and 70ºC. The structure of the hydrated kaolinite was characterized by X-ray diffraction and infrared spectroscopy. The morphology was examined using scanning electron microscopy. The results showed that the hydrated hydrazine of the transition phase was easy to decompose to hydrazines and water molecules in the interlayer at 40-70ºC. Hydrazine molecules de-intercalated gradually, and water molecules remained in the ditrigonal holes of the silicate layer with sufficient stability, finally forming the stable 0.84 nm hydrated kaolinite in the system with a success rate of 80–90%. The 0.84 nm hydrated kaolinite may become an excellent precursor for the preparation of other kaolinite intercalates. A degree of intercalation of ~100% was obtained for the kaolinite-ethylene glycol intercalate, and a degree of intercalation of ~80% was obtained for the kaolinite-glycine intercalate from the 0.84 nm hydrated kaolinite precursor.
Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China.
Method
Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment.
Results
The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = −3.161, p = 0.007] and 16 (LS mean difference = −3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed.
Conclusions
Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.
In this paper, we study the Friedrichs extensions of Sturm–Liouville operators with complex coefficients according to the classification of B. M. Brown et al. [3]. We characterize the Friedrichs extensions both by boundary conditions at regular endpoint and asymptotic behaviours of elements in the maximal operator domains at singular endpoint. Some of spectral properties are also involved.
Late Palaeozoic igneous rock associations in response to subduction, accretion, and final closure of the eastern Palaeo-Asian Ocean play a significant role in understanding the geodynamic evolution of the southeastern Central Asian Orogenic Belt. Previous studies have identified a Permian arc magmatic belt associated with the southward-dipping subduction of the eastern Palaeo-Asian Ocean along the Solonker–Changchun suture zone. The genetic mechanism and associated geodynamic settings are of great importance in deciphering the evolution of the eastern Palaeo-Asian Ocean. This paper presents zircon U–Pb–Hf isotope and whole-rock geochemical analyses for a suite of magmatic rocks including the early Permian diorite porphyrites (ca. 281.0 Ma), andesites (ca. 276 Ma) and rhyolites (ca. 275 Ma) in the Kulun region. The diorite porphyrites and andesites have high SiO2 and total alkali contents, and low MgO contents and Mg no. values, with enrichments in large ion lithophile elements and depletions in high-field-strength elements. These geochemical characteristics, together with low-Sr and high-Yb contents, a weak concave-upward shape of middle rare earth elements and negative Eu anomalies, suggest that these intermediate igneous rocks were generated by partial melting of amphibolitic lower crust at a crustal depth of 30–40 km. The rhyolites have heterogeneous isotopic compositions, with ϵHf(t) values and TDM2 ages of –20.8 to +0.5 and 3578∼1494 Ma, implying that they were likely derived from partial melting of a mixed source dominated by recycled ancient crust with minor juvenile crustal materials. The rhyolites show potassic affinity with relatively high K2O and very low Na2O, which was attributed to liquid immiscibility of felsic magma and subsequent limited fractional crystallization of plagioclase. The regional igneous associations, metamorphic events, and coeval sedimentary rocks along the Solonker–Changchun suture zone indicate that the early Permian igneous rocks were formed in an active continental arc environment in response to southward subduction of the eastern Palaeo-Asian Ocean.
Accumulating evidence suggests that supplementation of n-3 PUFA was associated with reduction in risk of major cardiovascular events. This meta-analysis was to systematically evaluate whether daily supplementation and accumulated intake of n-3 PUFA are associated with improved left ventricular (LV) remodelling in patients with chronic heart failure (CHF). Articles were obtained from Pubmed, Clinical key and Web of Science from inception to January 1 in 2021, and a total of twelve trials involving 2162 participants were eligible for inclusion. The sources of study heterogeneity were explained by I2 statistic and subgroup analysis. Compared with placebo groups, n-3 PUFA supplementation improved LV ejection fraction (LVEF) (eleven trials, 2112 participants, weighted mean difference (WMD) = 2·52, 95 % CI 1·25, 3·80, I2 = 87·8 %) and decreased LV end systolic volume (five studies, 905 participants, WMD = –3·22, 95 % CI 3·67, −2·77, I2 = 0·0 %) using the continuous variables analysis. Notably, the high accumulated n-3 PUFA dosage groups (≥ 600 g) presented a prominent improvement in LVEF, while the low and middle accumulated dosage (≤ 300 and 300–600 g) showed no effects on LVEF. In addition, n-3 PUFA supplementation decreased the levels of pro-inflammatory mediators including TNF-α, IL-6 (IL-6) and hypersensitive c-reactive protein. Therefore, the present meta-analysis demonstrated that n-3 PUFA consumption was associated with a substantial improvement of LV function and remodelling in patients subjected to CHF. The accumulated dosage of n-3 PUFA intake is vital for its cardiac protective role.
The gas hydrate stability zone (GHSZ) is the essential condition for gas hydrate accumulation, which is controlled by three main factors: gas component, geothermal gradient and permafrost thickness. Based on the gas component of hydrate samples from drilling in Muri coalfield, the gas hydrate phase equilibrium curve was calculated using Sloan's natural gas hydrate phase equilibrium procedure (CSMHYD) program. Through temperature data processing of coalfield boreholes, some important data such as thickness of permafrost and geothermal gradient were obtained. The GHSZ parameters of a single borehole were calculated by programming based on the above basic data. The average thickness of GHSZ of 85 boreholes in Muri coalfield amounted to approximately 1000 m, indicating very broad space for gas hydrate occurrence. The isogram of GHSZ bottom depth drawn from single borehole data in Muri coalfield demonstrated the regional distribution characteristics of GHSZ, and identified three favourable areas of gas hydrate occurrence where the bottom of GHSZ had a burial depth >1500 m – namely, the southern part of Juhugeng Mining Area, the middle part of Duosuogongma Mining Area and the eastern part of Xuehuoli Mining Area.
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.
Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).
Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.
The provenance and tectonic setting of the Lower–Middle Triassic clastic sediments from the Napo basin, South China, have been examined here using detrital modes, whole-rock geochemistry and detrital zircon U–Pb ages. Field investigations indicate that these sediments consist of fan delta, slope and turbidity fan facies with dominantly southward palaeocurrent directions. Detrital modes and geochemical characteristics of the clastic rocks indicate that they were derived from mixed magmatic arc and Palaeozoic successions in a continental island arc setting, with no significant sediment recycling. The U–Pb age spectra of sandstone detrital zircons from different stratigraphic positions are similar, with one major group (300–230 Ma), two subordinate groups (400–320 Ma and 480–420 Ma, respectively) and two scattered groups (1200–800 Ma and 2000–1700 Ma, respectively). Thus, we consider that the north late Permian – Middle Triassic volcanic rocks and the uplifted Palaeozoic sedimentary/volcanic sequences constituted the predominant sources. The detritus derived from the late Permian Emeishan mafic rocks is subordinate and limited. The pre-Devonian zircons are likely sedimentary-recycled or magmatic-captured instead of directly derived from the early Palaeozoic orogen (e.g. Yunkai massif) and Neoproterozoic Jiangnan orogen because of the topographic barrier of a magmatic arc and carbonate platform. Considering the spatial and temporal distribution characteristics of the volcanic arc and ophiolite, we suggest that the Triassic Napo basin was a fore-arc basin within a continental island arc setting, which developed in response to the northward subduction of the Babu–Cao Bang branch ocean beneath the South China Block.
A kind of tapered segmented cladding fiber (T-SCF) with large mode area (LMA) is proposed, and the mode and amplification characteristics of T-SCFs with concave, linear, and convex tapered structures are investigated based on finite-element method (FEM) and few-mode steady-state rate equation. Simulation results indicate that the concave tapered structure can introduce high loss for high-order modes (HOMs) that is advantageous to achieve single-mode operation, whereas the convex tapered structure provides large effective mode area that can help to mitigate nonlinear effects. Meanwhile, the small-to-large amplification scheme shows further advantages on stripping off HOMs, and the large-to-small amplification scheme decreases the heat load density induced by the high-power pump. Moreover, single-mode propagation performance, effective mode area, and heat load density of the T-SCF are superior to those of tapered step index fiber (T-SIF). These theoretical model and numerical results can provide instructive suggestions for designing high-power fiber lasers and amplifiers.
A 1178 J near diffraction limited 527 nm laser is realized in a complete closed-loop adaptive optics (AO) controlled off-axis multi-pass amplification laser system. Generated from a fiber laser and amplified by the pre-amplifier and the main amplifier, a 1053 nm laser beam with the energy of 1900 J is obtained and converted into a 527 nm laser beam by a KDP crystal with 62% conversion efficiency, 1178 J and beam quality of 7.93 times the diffraction limit (DL). By using a complete closed-loop AO configuration, the static and dynamic wavefront distortions of the laser system are measured and compensated. After correction, the diameter of the circle enclosing 80% energy is improved remarkably from 7.93DL to 1.29DL. The focal spot is highly concentrated and the 1178 J, 527 nm near diffraction limited laser is achieved.