F1000Research最新文献

{"title":"Impact of chlorine dioxide and chlorhexidine mouthwashes on friction and surface roughness of orthodontic stainless steel wires: an in-vitro comparative study.","authors":"Shivani Apte, Divya S, Arun S Urala","doi":"10.12688/f1000research.158974.2","DOIUrl":"https://doi.org/10.12688/f1000research.158974.2","url":null,"abstract":"<p><strong>Objectives: </strong>Good oral hygiene measures are important for successful orthodontic treatment. They involve various types of mouthwashes which have been reported to cause alteration of mechanical properties of archwires. This study aimed to evaluate the effects of a new kind of chlorine-dioxide-containing mouthwash on the mechanical properties and surface morphology of stainless steel orthodontic archwires against the already prevalent chlorhexidine mouthwash in the market.</p><p><strong>Method: </strong>Group A - Chlorhexidine mouthwash 0.2% (study), Group B - Chlorine Dioxide mouthwash (study), and Group C - Artificial Saliva (control). 42 specimens of 5 cm long 19x25 inch SS archwires were immersed in each group equally. Post immersion, the frictional force was analyzed in the universal testing machine for each group using custom-made acrylic jigs for 10 specimens. The remaining 4 specimens from each group were sent for surface morphology evaluation using an atomic force microscope.</p><p><strong>Results: </strong>Friction resistance evaluation for the archwires revealed a mean friction of 0.011 ± 0.0056 in Group A, 0.015 ± 0.0052 in Group B, and 0.010 ± 0.0067 in Group C. Results suggested that the static friction of Group C (control group) was found to be the least when compared with the experimental groups, although not producing statistically significant values. Surface roughness of archwires compared at a 10μm range revealed a mean roughness of 19.38 ± 0.82 in Group A, 25.39 ± 7.01 in Group B, and 16.65 ± 3.07 in Group C which shows there wasn't any statistically significant difference in the mean roughness midst the three sets.</p><p><strong>Conclusion: </strong>Chlorine dioxide and Chlorhexidine mouthwashes caused an increase in the frictional resistance of the archwires when compared to the control group. When measured at a range of 10μm the mean surface roughness did not differ across the control and the experimental groups.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"13 ","pages":"1442"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flexible modular dwelling for rural environments; specific case: Cebadas - Ecuador.","authors":"Karina Elizabeth Cajamarca Dacto, Jean Carlos Montero Riofrio, Erick Fabricio Nieto Páez, Dany Marcelo Tasan Cruz, Maikol Josueé González Espinosa","doi":"10.12688/f1000research.154417.2","DOIUrl":"https://doi.org/10.12688/f1000research.154417.2","url":null,"abstract":"<p><strong>Background: </strong>Sustainable modular dwelling design for rural areas should focus on creating healthy and economically accessible spaces, sensitive to local needs and integrating environmental, functional, sociological and technological aspects. Flexibility is essential to reduce the initial investment and allow future transformations, optimizing the recovery and reuse of materials. These houses must be adaptable, safe and have basic services, satisfying the needs and stages of families' development. In Ecuador, poverty and energy inefficiency worsen the quality of life in rural areas. This project in the Cebadas parish proposes modular dwelling that applies bioclimatic and sustainable criteria, using local materials to improve habitability and promote the social and economic development of the community.</p><p><strong>Method: </strong>The research approach is qualitative-quantitative. Qualitative, since it is necessary to identify the qualities of the sector, bibliographic exploration of guidelines and sustainable strategies. Quantitative, to evaluate the degree of affectation through a diagnosis of the study site and to provide efficient solutions that respond to the context and social reality.</p><p><strong>Results: </strong>The spaces presented in the proposal respond to the spatial need for growth and expansion of the users of the sector, through 6 basic guidelines that this type of dwelling should have: Environment, Visual, Form, Function, Bioclimatic and Materials.</p><p><strong>Conclusions: </strong>The flexible modular dwelling project for rural environments addresses complex housing needs, highlighting the flexibility and adaptability of an expandable module. It includes income generation with a duplex apartment, fosters communal and cultural life with public and commercial spaces, promotes tourism and rural development with landscape design and crops. In addition, it ensures sustainability through bioclimatic strategies and responsible use of resources.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"13 ","pages":"845"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotoxic effects in island populations of Cartagena de Indias, Colombia due to environmental exposure to mercury and cadmium.","authors":"Eder Cano-Pérez, Doris Gómez-Camargo, Dacia Malambo-García","doi":"10.12688/f1000research.154617.3","DOIUrl":"10.12688/f1000research.154617.3","url":null,"abstract":"<p><strong>Background: </strong>Contamination of Cartagena Bay, Colombia with heavy metals such as mercury (Hg) and cadmium (Cd) presents a major environmental and public health concern, particularly for human communities residing on nearby islands and coastal areas. These populations face enhanced exposure risks owing to their traditional fishing practices and continuous interactions with polluted marine environments. This study aimed to evaluate the genotoxic effects of environmental exposure to Hg and Cd in populations from the island zone of the Cartagena district, Bolívar.</p><p><strong>Methods: </strong>Ninety-four individuals from the four island communities (study group) and 30 individuals from the urban area of Cartagena (control group) participated in this study. The blood samples were collected to measure total mercury (T-Hg) and Cd concentrations, and a Buccal Micronucleus Cytome (BMCyt) assay was used to evaluate exposure effects.</p><p><strong>Results: </strong>Cadmiun levels in the blood of the study group were within the normal range and comparable to those of the control group (p > 0.05). However, the study group exhibited significantly higher T-Hg levels (7.34 μg/L) compared to the control group (2.01 μg/L), surpassing the accepted limit. Moreover, the study group showed a higher incidence of DNA damage and cell death biomarkers (p < 0.05). Additionally, significant correlations were observed between total blood Hg levels and the frequencies of micronuclei, karyorrhexis, and karyolysis.</p><p><strong>Conclusion: </strong>These results suggest that island populations of Cartagena are exposed to high levels of Hg and exhibit genotoxic damage, indicating a problem that must be addressed.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"13 ","pages":"946"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP2C19 polymorphism and coronary in-stent restenosis: A systematic review and meta-analysis.","authors":"Yusra Pintaningrum, Vitriyaturrida, Ivana Purnama Dewi, Hendy Bhaskara Perdana Putra, Idar Mappangara, Muzakkir Amir, Irawan Yusuf, Agussalim Bukhari","doi":"10.12688/f1000research.109321.2","DOIUrl":"10.12688/f1000research.109321.2","url":null,"abstract":"<p><strong>Background: </strong>In-stent restenosis (ISR) remains a major drawback in coronary stenting. The association between the CYP2C19 loss of function (LOF) gene and the prevalence of ISR after coronary stenting remains controversial. Previous studies have produced conflicting results and have been limited by their small population sizes. We conducted this systematic review and meta-analysis to determine the association between the presence of the CYP2C19 LOF gene and the prevalence of ISR.</p><p><strong>Methods: </strong>A systematic online database search was performed until April 2021. The primary outcome was ISR and assessed using OR with 95% CI. Quality of the study was assessed using the Newcastle Ottawa Scale. <i>I ²</i> was applied to examine heterogeneities among the studies.</p><p><strong>Results: </strong>A total of 284 patients (four non-randomized controlled trial studies) were included in this study. Two hundred and six patients had wild-type genotypes, while 78 patients had the LOF genotype. Among the 78 patients with the LOF gene, 38 patients had an ISR. Meanwhile, of the 206 patients with a wild-type gene, 69 patients had an ISR. LOF gene was associated with a higher risk of ISR (OR 95% CI = 2.71 [1.42-5.16], P = 0.003). However, study-specific variability should be considered when applying these findings clinically.</p><p><strong>Conclusions: </strong>Patients with LOF genes, regardless of the allele variation, treated with clopidogrel, had a higher likelihood of ISR after coronary stenting.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"11 ","pages":"346"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential gene expression during recall of behaviorally conditioned immune enhancement in rats: a pilot study.","authors":"Markus Rueckels, Marcus Picard-Mareau","doi":"10.12688/f1000research.123975.1","DOIUrl":"10.12688/f1000research.123975.1","url":null,"abstract":"<p><strong>Background: </strong>Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system <i>via</i> the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that.</p><p><strong>Methods: </strong>Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis.</p><p><strong>Results: </strong>In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma.</p><p><strong>Conclusions: </strong>Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":" ","pages":"1405"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45824835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of MR Finger printing derived T1 and T2 values in Adult brain: A Systematic review.","authors":"Riyan Mohamed Sajer, Saikiran Pendem, Rajagopal Kadavigere, Priyanka -, Shailesh Nayak S, Kaushik Nayak, Tancia Pires, Obhuli Chandran M, Abhijith S, Varsha Raghu","doi":"10.12688/f1000research.160088.1","DOIUrl":"10.12688/f1000research.160088.1","url":null,"abstract":"<p><strong>Introduction: </strong>Magnetic resonance imaging (MRI) is essential for brain imaging, but conventional methods rely on qualitative contrast, are time-intensive, and prone to variability. Magnetic resonance finger printing (MRF) addresses these limitations by enabling fast, simultaneous mapping of multiple tissue properties like T1, T2. Using dynamic acquisition parameters and a precomputed signal dictionary, MRF provides robust, qualitative maps, improving diagnostic precision and expanding clinical and research applications in brain imaging.</p><p><strong>Methods: </strong>Database searches were performed through PubMed, Embase, Scopus, Web of science to identify relevant articles focusing on the application of MR finger printing in the adult brain. We utilized the preferred reporting items for systematic reviews and meta-analysis guidelines to extract data from the selected studies.</p><p><strong>Results: </strong>Nine articles were included in the final review, with a total sample size of 332 participants. In healthy brains, notable regional, sex, age, and hemispheric variations were identified, particularly in the corpus callosum and thalamus. MRF effectively differentiated meningioma subtypes, glioma grades, and IDH mutation status, with T2 values providing particularly predictive for glioma classification. In brain metastases, significant relaxometry differences were noted between normal and lesional tissues. For multiple sclerosis, MRF values correlated with clinical and disability measures, distinguishing relapsing-remitting secondary progressive forms. In traumatic brain injury, longitudinal T1 changes strongly correlated with clinical recovery, surpassing T2 values.</p><p><strong>Conclusions: </strong>The systematic review highlighted MRD as a groundbreaking technique that enhances neurological diagnosis by simultaneously quantifying T1 and T2 relaxation times. With reduced acquisition times, MRF outperforms conventional MRI in detecting subtle pathologies, distinguishing properties, and providing reliable biomarkers.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"14 ","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of MAP2, GFAP, and calcium in the CA3 Region Following Kainic Acid Exposure to  organotypic hippocampal slice culture.","authors":"Machlusil Husna, Kusworini Handono, Hidayat Sujuti, Aulanni'am Aulanni'am, Ettie Rukmigarsari","doi":"10.12688/f1000research.126732.3","DOIUrl":"https://doi.org/10.12688/f1000research.126732.3","url":null,"abstract":"<p><strong>Background: </strong>Neurodegeneration due to neurotoxicity is one of the phenomena in temporal lobe epilepsy. Experimentally, hippocampal excitotoxicity process can occur due to kainic acid exposure, especially in the CA3 area. Neuronal death, astrocyte reactivity and increased calcium also occur in hippocampal excitotoxicity, but few studies have investigated immediate effect after kainic acid exposure. The organotypic hippocampal slice culture (OHSC) is a useful model for studying the neurodegeneration process, but there are still many protocol differences. In this study, minor modifications were made in the OHSC protocol.</p><p><strong>Methods: </strong>OHSC was obtained from three healthy wild type Wistar rats aged P10. Healthy culture slices were obtained and lasted up to 10 days <i>in vitro</i> (DIV 10). Bath application of kainic acid for 48 hours in DIV 10 followed by observation of its initial effects on neurons, astrocytes, and calcium via the expression of MAP2, GFAP, and intracellular calcium imaging, subsequently.</p><p><strong>Results: </strong>After 48 h of kainic acid administration, there was a significant increase in intracellular calcium intensity (p = 0.006 < α), accompanied by a significant decrease in MAP2 (p = 0.003 < α) and GFAP (p = 0.010 < α) expression.</p><p><strong>Conclusion: </strong>These findings suggest early neuronal and astrocyte damage at the initial onset of hippocampal injury. This implies that astrocyte damage occurs early before an increase in GFAP that characterizes reactive astrogliosis found in other studies. Damage to neurons and astrocytes may be associated with increased intracellular calcium. It is necessary to develop further research regarding regulation of calcium, MAP2, and GFAP at a spatial time after exposure to kainic acid and strategies to reduce damage caused by excitotoxicity.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"12 ","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Through restful waters and deep commotion: A study on burnout and health impairment of Italian seafarers from the JD-R model perspective.","authors":"Francesco Buscema, Lorenzo Cena, Clarissa Cricenti, Margherita Zito, Lara Bertola, Lara Colombo","doi":"10.12688/f1000research.159198.1","DOIUrl":"10.12688/f1000research.159198.1","url":null,"abstract":"<p><strong>Background: </strong>The work experience of seafarers differs significantly from other land-based occupations due to several factors, particularly remoteness and the restricted work environment. This study seeks to examine the impact of burnout and health impairment in the maritime industry, using the Job Demand-Resources theory as a framework.</p><p><strong>Methods: </strong>To investigate these phenomena, an online questionnaire was sent to 239 Italian seafarers (94.6% men, Mage = 39.44, SD = 12.8). We tested a mediated Structural Equation Model (SEM) aimed at predicting negative health outcomes.</p><p><strong>Results: </strong>The results show that burnout plays a mediating role between job demands (such as workload and cognitive strain) and resources (such as social support and transformational leadership), influencing variables related to health impairment (such as sleep quality and physical well-being). Furthermore, the findings highlight the direct influence of occupational resources on seafarers' health.</p><p><strong>Conclusions: </strong>The discussion highlights the urgent need for more research in the field of organisational psychology in the maritime industry and the discrepancies between these findings, which are consistent with the existing maritime literature, and other studies that do not include seafarers in their sample groups.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"14 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences of Students with Disabilities Enrolling in Higher Education: A Qualitative Study in the United Arab Emirates.","authors":"Muhammad Arsyad Subu, Richard Mottershead, Ahmed Mahmoud Sallam, Jacqueline Maria Dias, Janisha Kavumpurath, Fatma Refaat Ahmed, Heba Hesham Hijazi, Mini Sara Abraham, Alounoud Mohamed Al Marzouqi, Vidya Seshan, Shahd Mohammed Elabed, Ahmad Rajeh Saifan, Syed Azizur Rahman, Nabeel Al Yateem","doi":"10.12688/f1000research.158481.1","DOIUrl":"https://doi.org/10.12688/f1000research.158481.1","url":null,"abstract":"<p><strong>Background: </strong>Higher education is experiencing an increase in students with disabilities, necessitating considering their interests and well-being when preparing educational services. Students with disabilities make up one of the most significant minority groups among students in terms of diversity.</p><p><strong>Aims: </strong>This study explored the experiences of students with disabilities at a university in the United Arab Emirates. It also aimed to understand students with disabilities' social and academic experiences and the factors affecting their university persistence.</p><p><strong>Methods: </strong>We used a descriptive qualitative research approach to understand how students with disabilities experience the phenomenon under study. Twenty-five students participated, chosen via purposeful sampling. The data was collected using semi-structured interviews, which were analyzed using content analysis.</p><p><strong>Results: </strong>We found four themes that emerged from this study: (1) perceptions about the university, (2) socialization and integration, (3) barriers to the university journey, and (4) support for the journey.</p><p><strong>Conclusion: </strong>We found that students with disabilities indicated positive and negative perspectives and experiences. We recommend modifying the physical, social, and educational environments to support the education of students with disabilities. Future studies should employ a more varied sample and include academics and students to collect different perspectives while stressing the students' experiences.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"14 ","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis.","authors":"Spyridon Siafis, Nobuyuki Nomura, Johannes Schneider-Thoma, Irene Bighelli, Alexandra Bannach-Brown, Fiona J Ramage, Francesca Tinsdeall, Ioannis Mantas, Sameer Jauhar, Sridhar Natesan, Anthony C Vernon, Andrea de Bartolomeis, Sabine M Hölter, Natascha I Drude, Ulf Tölch, Wulf-Peter Hansen, Virginia Chiocchia, Oliver D Howes, Josef Priller, Malcolm R Macleod, Georgia Salanti, Stefan Leucht","doi":"10.12688/f1000research.155356.2","DOIUrl":"10.12688/f1000research.155356.2","url":null,"abstract":"<p><strong>Background: </strong>Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.</p><p><strong>Methods: </strong>We plan a systematic review and meta-analysis of <i>in vivo</i> animal studies comparing muscarinic receptor agonists or positive allosteric modulators with control conditions and existing D2R-blocking antipsychotics in animals subjected to any method that induces behavioural changes of relevance for psychosis. We will identify eligible studies by searching multiple electronic databases. At least two independent reviewers will conduct the study selection and data extraction using prespecified forms and assess the risk of bias with the SYRCLE's tool. Our primary outcomes include locomotor activity and prepulse inhibition measured with standardized mean differences. We will examine other behavioural readouts of relevance for psychosis as secondary outcomes, such as social interaction and cognitive function. We will synthesize the data using multi-level meta-analysis with a predefined random-effects structure, considering the non-independence of the data. In meta-regressions we will explore potential sources of heterogeneity from a predefined list of characteristics of the animal population, model, and intervention. We will assess the confidence in the evidence considering a self-developed instrument thatconsiders the internal and external validity of the evidence.</p><p><strong>Protocol registration: </strong>PROSPERO-ID: CRD42024520914.</p>","PeriodicalId":12260,"journal":{"name":"F1000Research","volume":"13 ","pages":"1017"},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}