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1.
Mol Biol Rep ; 51(1): 300, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349603

RESUMO

BACKGROUND: Doxorubicin (DOX) may cause various neurological side effects in the brain. Lercanidipine (LRD) has antioxidant, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the potential benefits of. METHODS AND RESULTS: Lercanidipine in reducing doxorubicin-induced neuroinflammation and maintaining the expressions of choline acetyltransferase. Thirty-two adult Wistar albino female rats were divided into four groups as Control, DOX (20 mg/kg intraperitoneally), DOX + LRD 0.5 (0.5 mg/kg orally), and DOX + LRD2(2 mg/kg orally). Twenty-four hours after the last drug administration (9th day), brain tissues were taken for histopathological, immunohistochemical (choline acetyltransferase [CHAT], interleukin-10 [IL-10], and caspase-3 [Cas-3] staining), biochemical (total antioxidant status [TAS], total oxidant status [TOS], and oxidative stress index [OSI]), and genetic analyzes (PI3K/AKT/HIF1-α and IL-6 gene expressions). Histopathological analyses revealed hyperemia, slight hemorrhage, degeneration, neuronal loss, gliosis in the cerebellum, and neuronal loss in the brain cortex and hippocampus in the DOX group. According to other analyzes, decreased CHAT, PI3K, AKT, HIF1-α and increased IL-6, IL-10, Cas-3 expression were observed in the DOX group. CONCLUSIONS: Both LRD doses reversed all these findings, but LRD2 was observed to be more effective. In conclusion, we determined that LRD has potential therapeutic effect by reducing DOX-induced neuroinflammation, oxidative stress and apoptosis in brain tissues.


Assuntos
Colina O-Acetiltransferase , Di-Hidropiridinas , Interleucina-10 , Animais , Ratos , Ratos Wistar , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Antioxidantes/farmacologia , Interleucina-6 , Doenças Neuroinflamatórias , Doxorrubicina/efeitos adversos
2.
J Comp Neurol ; 532(2): e25587, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38335048

RESUMO

We examined the presence/absence and parcellation of cholinergic neurons in the hypothalami of five birds: a Congo grey parrot (Psittacus erithacus), a Timneh grey parrot (P. timneh), a pied crow (Corvus albus), a common ostrich (Struthio camelus), and an emu (Dromaius novaehollandiae). Using immunohistochemistry to an antibody raised against the enzyme choline acetyltransferase, hypothalamic cholinergic neurons were observed in six distinct clusters in the medial, lateral, and ventral hypothalamus in the parrots and crow, similar to prior observations made in the pigeon. The expression of cholinergic nuclei was most prominent in the Congo grey parrot, both in the medial and lateral hypothalamus. In contrast, no evidence of cholinergic neurons in the hypothalami of either the ostrich or emu was found. It is known that the expression of sleep states in the ostrich is unusual and resembles that observed in the monotremes that also lack hypothalamic cholinergic neurons. It has been proposed that the cholinergic system acts globally to produce and maintain brain states, such as those of arousal and rapid-eye-movement sleep. The hiatus in the cholinergic system of the ostrich, due to the lack of hypothalamic cholinergic neurons, may explain, in part, the unusual expression of sleep states in this species. These comparative anatomical and sleep studies provide supportive evidence for global cholinergic actions and may provide an important framework for our understanding of one broad function of the cholinergic system and possible dysfunctions associated with global cholinergic neural activity.


Assuntos
Dromaiidae , Struthioniformes , Animais , Dromaiidae/metabolismo , Struthioniformes/metabolismo , Encéfalo/metabolismo , Hipotálamo/metabolismo , Neurônios Colinérgicos/metabolismo , Sono/fisiologia , Colinérgicos , Colina O-Acetiltransferase/metabolismo
3.
Nutrients ; 16(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38398794

RESUMO

The chatbot Chat Generative Pretrained Transformer (ChatGPT) is becoming increasingly popular among patients for searching health-related information. Prior studies have raised concerns regarding accuracy in offering nutritional advice. We investigated in November 2023 ChatGPT's potential as a tool for providing nutritional guidance in relation to different non-communicable diseases (NCDs). First, the dietary advice given by ChatGPT (version 3.5) for various NCDs was compared with guidelines; then, the chatbot's capacity to manage a complex case with several diseases was investigated. A panel of nutrition experts assessed ChatGPT's responses. Overall, ChatGPT offered clear advice, with appropriateness of responses ranging from 55.5% (sarcopenia) to 73.3% (NAFLD). Only two recommendations (one for obesity, one for non-alcoholic-fatty-liver disease) contradicted guidelines. A single suggestion for T2DM was found to be "unsupported", while many recommendations for various NCDs were deemed to be "not fully matched" to the guidelines despite not directly contradicting them. However, when the chatbot handled overlapping conditions, limitations emerged, resulting in some contradictory or inappropriate advice. In conclusion, although ChatGPT exhibited a reasonable accuracy in providing general dietary advice for NCDs, its efficacy decreased in complex situations necessitating customized strategies; therefore, the chatbot is currently unable to replace a healthcare professional's consultation.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Doenças não Transmissíveis , Humanos , Educação em Saúde , Colina O-Acetiltransferase , Instalações de Saúde , Doenças não Transmissíveis/prevenção & controle
4.
Hum Gene Ther ; 35(3-4): 123-131, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38299967

RESUMO

The enzyme choline acetyltransferase (ChAT) synthesizes acetylcholine from acetyl-CoA and choline at the neuromuscular junction and at the nerve terminals of cholinergic neurons. Mutations in the ChAT gene (CHAT) result in a presynaptic congenital myasthenic syndrome (CMS) that often associates with life-threatening episodes of apnea. Knockout mice for Chat (Chat-/-) die at birth. To circumvent the lethality of this model, we crossed mutant mice possessing loxP sites flanking Chat exons 4 and 5 with mice that expressed Cre-ERT2. Injection of tamoxifen (Tx) at postnatal (P) day 11 in these mice induced downregulation of Chat, autonomic failure, weakness, and death. However, a proportion of Chatflox/flox-Cre-ERT2 mice receiving at birth an intracerebroventricular injection of 2 × 1013 vg/kg adeno-associated virus type 9 (AAV9) carrying human CHAT (AAV9-CHAT) survived a subsequent Tx injection and lived to adulthood without showing signs of weakness. Likewise, injection of AA9-CHAT by intracisternal injection at P28 after the onset of weakness also resulted in survival to adulthood. The expression of Chat in spinal motor neurons of Chatflox/flox-Cre-ERT2 mice injected with Tx was markedly reduced, but AAV-injected mice showed a robust recovery of ChAT expression, which was mainly translated by the human CHAT RNA. The biodistribution of the viral genome was widespread but maximal in the spinal cord and brain of AAV-injected mice. No significant histopathological changes were observed in the brain, liver, and heart of AAV-injected mice after 1 year follow-up. Thus, AAV9-mediated gene therapy may provide an effective and safe treatment for patients severely affected with CHAT-CMS.


Assuntos
Colina O-Acetiltransferase , Dependovirus , Camundongos , Humanos , Animais , Colina O-Acetiltransferase/genética , Colina O-Acetiltransferase/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Distribuição Tecidual , Camundongos Knockout , Terapia Genética
5.
PLoS One ; 19(2): e0298427, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358993

RESUMO

BACKGROUND: Generative Artificial Intelligence (AI) technology, for instance Chat Generative Pre-trained Transformer (ChatGPT), is continuously evolving, and its userbase is growing. These technologies are now being experimented by the businesses to leverage their potential and minimise their risks in business operations. The continuous adoption of the emerging Generative AI technologies will help startups gain more and more experience with adoptions, helping them to leverage continuously evolving technological innovation landscape. However, there is a dearth of prior research on ChatGPT adoption in the startup context, especially from Entrepreneur perspective, highlights the urgent need for a thorough investigation to identify the variables influencing this technological adoption. The primary objective of this study is to ascertain the factors that impact the uptake of ChatGPT technology by startups, anticipate their influence on the triumph of companies, and offer pragmatic suggestions for various stakeholders, including entrepreneurs, and policymakers. METHOD AND ANALYSIS: This study attempts to explore the variables impacting startups' adoption of ChatGPT technology, with an emphasis on comprehending entrepreneurs' attitudes and perspectives. To identify and then empirically validate the Generative AI technology adoption framework, the study uses a two-stage methodology that includes experience-based research, and survey research. The research method design is descriptive and Correlational design. Stage one of the research study is descriptive and involves adding practical insights, and real-world context to the model by drawing from the professional consulting experiences of the researchers with the SMEs. The outcome of this stage is the adoption model (also called as research framework), building Upon Technology Adoption Model (TAM), that highlight the technology adoption factors (also called as latent variables) connected with subset of each other and finally to the technology adoption factor (or otherwise). Further, the latent variables and their relationships with other latent variables as graphically highlighted by the adoption model will be translated into the structured questionnaire. Stage two involves survey based research. In this stage, structured questionnaire is tested with small group of entrepreneurs (who has provided informed consent) and finally to be distributed among startup founders to further validate the relationships between these factors and the level of influence individual factors have on overall technology adoption. Partial Least Squares Structural Equation Modeling (PLS-SEM) will be used to analyze the gathered data. This multifaceted approach allows for a comprehensive analysis of the adoption process, with an emphasis on understanding, describing, and correlating the key elements at play. DISCUSSION: This is the first study to investigate the factors that impact the adoption of Generative AI, for instance ChatGPT technology by startups from the Entrepreneurs perspectives. The study's findings will give Entrepreneurs, Policymakers, technology providers, researchers, and Institutions offering support for entrepreneurs like Academia, Incubators and Accelerators, University libraries, public libraries, chambers of commerce, and foreign embassies important new information that will help them better understand the factors that encourage and hinder ChatGPT adoption. This will allow them to make well-informed strategic decisions about how to apply and use this technology in startup settings thereby improving their services for businesses.


Assuntos
Inteligência Artificial , Tecnologia , Humanos , Transporte Biológico , Colina O-Acetiltransferase , Comércio
6.
Sci Rep ; 14(1): 243, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167988

RESUMO

Hypothyroidism is characterized by thyroid hormone deficiency and has adverse effects on both pregnancy and fetal health. Chat Generative Pre-trained Transformer (ChatGPT) is a large language model trained with a very large database from many sources. Our study was aimed to evaluate the reliability and readability of ChatGPT-4 answers about hypothyroidism in pregnancy. A total of 19 questions were created in line with the recommendations in the latest guideline of the American Thyroid Association (ATA) on hypothyroidism in pregnancy and were asked to ChatGPT-4. The reliability and quality of the responses were scored by two independent researchers using the global quality scale (GQS) and modified DISCERN tools. The readability of ChatGPT was assessed used Flesch Reading Ease (FRE) Score, Flesch-Kincaid grade level (FKGL), Gunning Fog Index (GFI), Coleman-Liau Index (CLI), and Simple Measure of Gobbledygook (SMOG) tools. No misleading information was found in any of the answers. The mean mDISCERN score of the responses was 30.26 ± 3.14; the median GQS score was 4 (2-4). In terms of reliability, most of the answers showed moderate (78.9%) followed by good (21.1%) reliability. In the readability analysis, the median FRE was 32.20 (13.00-37.10). The years of education required to read the answers were mostly found at the university level [9 (47.3%)]. Although ChatGPT-4 has significant potential, it can be used as an auxiliary information source for counseling by creating a bridge between patients and clinicians about hypothyroidism in pregnancy. Efforts should be made to improve the reliability and readability of ChatGPT.


Assuntos
Letramento em Saúde , Hipotireoidismo , Humanos , Estados Unidos , Gravidez , Feminino , Compreensão , Reprodutibilidade dos Testes , Leitura , Colina O-Acetiltransferase , Internet
7.
JMIR Med Educ ; 10: e51247, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180787

RESUMO

BACKGROUND: The use of artificial intelligence (AI) in medicine not only directly impacts the medical profession but is also increasingly associated with various potential ethical aspects. In addition, the expanding use of AI and AI-based applications such as ChatGPT demands a corresponding shift in medical education to adequately prepare future practitioners for the effective use of these tools and address the associated ethical challenges they present. OBJECTIVE: This study aims to explore how medical students from Germany, Austria, and Switzerland perceive the use of AI in medicine and the teaching of AI and AI ethics in medical education in accordance with their use of AI-based chat applications, such as ChatGPT. METHODS: This cross-sectional study, conducted from June 15 to July 15, 2023, surveyed medical students across Germany, Austria, and Switzerland using a web-based survey. This study aimed to assess students' perceptions of AI in medicine and the integration of AI and AI ethics into medical education. The survey, which included 53 items across 6 sections, was developed and pretested. Data analysis used descriptive statistics (median, mode, IQR, total number, and percentages) and either the chi-square or Mann-Whitney U tests, as appropriate. RESULTS: Surveying 487 medical students across Germany, Austria, and Switzerland revealed limited formal education on AI or AI ethics within medical curricula, although 38.8% (189/487) had prior experience with AI-based chat applications, such as ChatGPT. Despite varied prior exposures, 71.7% (349/487) anticipated a positive impact of AI on medicine. There was widespread consensus (385/487, 74.9%) on the need for AI and AI ethics instruction in medical education, although the current offerings were deemed inadequate. Regarding the AI ethics education content, all proposed topics were rated as highly relevant. CONCLUSIONS: This study revealed a pronounced discrepancy between the use of AI-based (chat) applications, such as ChatGPT, among medical students in Germany, Austria, and Switzerland and the teaching of AI in medical education. To adequately prepare future medical professionals, there is an urgent need to integrate the teaching of AI and AI ethics into the medical curricula.


Assuntos
Medicina , Estudantes de Medicina , Humanos , Estudos Transversais , Inteligência Artificial , Escolaridade , Colina O-Acetiltransferase
8.
Cell Tissue Res ; 395(1): 39-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37982872

RESUMO

The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the enteric nervous system (ENS), the major regulator of gastrointestinal functions. This study focused on the quantification and neurochemical characterization of substance P (SP) neurons in the pig ascending (AC) and descending colon (DC) in wholemount preparations of the inner submucosal plexus (ISP), outer submucosal plexus (OSP), and myenteric plexus (MP). We used antibodies for the pan-neuronal marker HuCD, and choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS), markers for excitatory and inhibitory transmitters, for multiple labeling immunofluorescence and high-resolution confocal microscopy. The highest density of SP immunoreactive (IR) neurons was in the ISP (222/mm2 in the AC, 166/mm2 in the DC), where they make up about a third of HuCD-IR neurons, compared to the OSP and MP (19-22% and 13-17%, respectively, P < 0.001-0.0001). HuCD/SP/ChAT-IR neurons (up to 23%) were overall more abundant than HuCD/SP/nNOS-IR neurons (< 10%). Most SP-IR neurons contained ChAT-IR (62-85%), whereas 18-38% contained nNOS-IR with the highest peak in the OSP. A subpopulation of SP-IR neurons contains both ChAT- and nNOS-IR with the highest peak in the OSP and ISP of DC (33-36%) and the lowest in the ISP of AC (< 10%, P < 0.001). SP-IR varicose fibers were abundant in the ganglia. This study shows that SP-IR neurons are functionally distinct with variable proportions in different plexuses in the AC and DC reflecting diverse functions of specific colonic regions.


Assuntos
Plexo Mientérico , Plexo Submucoso , Humanos , Suínos , Animais , Substância P , Neurônios , Colo , Colina O-Acetiltransferase
9.
J Intern Med ; 295(3): 346-356, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38011942

RESUMO

BACKGROUND: Choline acetyltransferase (ChAT) is required for the biosynthesis of acetylcholine, the molecular mediator that inhibits cytokine production in the cholinergic anti-inflammatory pathway of the vagus nerve inflammatory reflex. Abundant work has established the biology of cytoplasmic ChAT in neurons, but much less is known about the potential presence and function of ChAT in the extracellular milieu. OBJECTIVES: We evaluated the hypothesis that extracellular ChAT activity responds to inflammation and serves to inhibit cytokine release and attenuate inflammation. METHODS: After developing novel methods for quantification of ChAT activity in plasma, we determined whether ChAT activity changes in response to inflammatory challenges. RESULTS: Active ChAT circulates within the plasma compartment of mice and responds to immunological perturbations. Following the administration of bacterial endotoxin, plasma ChAT activity increases for 12-48 h, a time period that coincides with declining tumor necrosis factor (TNF) levels. Further, a direct activation of the cholinergic anti-inflammatory pathway by vagus nerve stimulation significantly increases plasma ChAT activity, whereas the administration of bioactive recombinant ChAT (r-ChAT) inhibits endotoxin-stimulated TNF production and anti-ChAT antibodies exacerbate endotoxin-induced TNF levels, results of which suggest that ChAT activity regulates endogenous TNF production. Administration of r-ChAT significantly attenuates pro-inflammatory cytokine production and disease activity in the dextran sodium sulfate preclinical model of inflammatory bowel disease. Finally, plasma ChAT levels are also elevated in humans with sepsis, with the highest levels observed in a patient who succumbed to infection. CONCLUSION: As a group, these results support further investigation of ChAT as a counter-regulator of inflammation and potential therapeutic agent.


Assuntos
Acetilcolina , Colina O-Acetiltransferase , Humanos , Colina O-Acetiltransferase/metabolismo , Inflamação , Fator de Necrose Tumoral alfa/metabolismo , Citocinas , Endotoxinas
10.
J Comp Neurol ; 532(2): e25570, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38108576

RESUMO

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented. The number and density of the labeled neurons were obtained by stringent stereological methods, whereas their topographical distribution was reported upon corresponding magnetic resonance imaging (MRI) planes. In both human and nonhuman primates, the PPN and LDTg are populated by three neurochemically distinct types of neurons (ChAT-/Nadph-δ+, ChAT+/Nadph-δ-, and ChAT+/Nadph-δ+), which are distributed according to a complex spatial interplay. Three-dimensional reconstructions reveal that ChAT+ neurons in the PPN and LDTg form a continuum with some overlaps with pigmented neurons of the locus coeruleus, dorsally, and of the substantia nigra (SN) complex, ventrally. The ChAT+ neurons in the PPN and LDTg are -two to three times more numerous in humans than in monkeys but their density is -three to five times higher in monkeys than in humans. Neurons expressing both ChAT and Nadph-δ have a larger cell body and a longer primary dendritic arbor than singly labeled neurons. Stereological quantification reveals that 25.6% of ChAT+ neurons in the monkey PPN are devoid of Nadph-δ staining, a finding that questions the reliability of Nadph-δ as a marker for cholinergic neurons in primate brainstem.


Assuntos
Tronco Encefálico , Tegmento Mesencefálico , Animais , Humanos , Reprodutibilidade dos Testes , Tronco Encefálico/metabolismo , Neurônios Colinérgicos/metabolismo , Colinérgicos , Colina O-Acetiltransferase/metabolismo
11.
Cells ; 12(23)2023 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-38067139

RESUMO

Major features of aging might be progressive decreases in cognitive function and physical activity, in addition to withered appearance. Previously, we reported that the intracerebroventricular injection of human neural stem cells (NSCs named F3) encoded the choline acetyltransferase gene (F3.ChAT). The cells secreted acetylcholine and growth factors (GFs) and neurotrophic factors (NFs), thereby improving learning and memory function as well as the physical activity of aged animals. In this study, F344 rats (10 months old) were intravenously transplanted with F3 or F3.ChAT NSCs (1 × 106 cells) once a month to the 21st month of age. Their physical activity and cognitive function were investigated, and brain acetylcholine (ACh) and cholinergic and dopaminergic system markers were analyzed. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both cognitive and physical functions, in parallel with the elevation in ACh levels in cerebrospinal fluid and muscles, in which F3.ChAT cells were more effective than F3 parental cells. Stem cell transplantation downregulated CCL11 and recovered GFs and NFs in the brain, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, along with neovascularization. Stem cells also restored muscular GFs and NFs, resulting in increased angiogenesis and muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage to the brain and muscles. The results indicate that NSCs encoding ChAT improve cognitive function and physical activity of aging animals by protecting and recovering functions of multiple organs, including cholinergic and dopaminergic systems, as well as muscles from oxidative injuries through secretion of ACh and GFs/NFs, increased antioxidant elements, and enhanced blood flow.


Assuntos
Acetilcolina , Células-Tronco Neurais , Ratos , Animais , Humanos , Masculino , Idoso , Lactente , Ratos Endogâmicos F344 , Acetilcolina/metabolismo , Colina O-Acetiltransferase/genética , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/farmacologia , Aprendizagem em Labirinto/fisiologia , Envelhecimento/fisiologia , Células-Tronco Neurais/metabolismo , Administração Intravenosa , Colinérgicos
12.
Neurobiol Dis ; 188: 106332, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37890559

RESUMO

Down syndrome (DS) is a genetic disorder caused by triplication of human chromosome 21. In addition to intellectual disability, DS is defined by a premature aging phenotype and Alzheimer's disease (AD) neuropathology, including septohippocampal circuit vulnerability and degeneration of basal forebrain cholinergic neurons (BFCNs). The Ts65Dn mouse model recapitulates key aspects of DS/AD pathology, namely age-associated atrophy of BFCNs and cognitive decline in septohippocampal-dependent behavioral tasks. We investigated whether maternal choline supplementation (MCS), a well-tolerated treatment modality, protects vulnerable BFCNs from age- and genotype-associated degeneration in trisomic offspring. We also examined the effect of trisomy, and MCS, on GABAergic basal forebrain parvalbumin neurons (BFPNs), an unexplored neuronal population in this DS model. Unbiased stereological analyses of choline acetyltransferase (ChAT)-immunoreactive BFCNs and parvalbumin-immunoreactive BFPNs were conducted using confocal z-stacks of the medial septal nucleus and the vertical limb of the diagonal band (MSN/VDB) in Ts65Dn mice and disomic (2N) littermates at 3-4 and 10-12 months of age. MCS trisomic offspring displayed significant increases in ChAT-immunoreactive neuron number and density compared to unsupplemented counterparts, as well as increases in the area of the MSN/VDB occupied by ChAT-immunoreactive neuropil. MCS also rescued BFPN number and density in Ts65Dn offspring, a novel rescue of a non-cholinergic cell population. Furthermore, MCS prevented age-associated loss of BFCNs and MSN/VDB regional area in 2N offspring, indicating genotype-independent neuroprotective benefits. These findings demonstrate MCS provides neuroprotection of vulnerable BFCNs and non-cholinergic septohippocampal BFPNs, indicating this modality has translational value as an early life therapy for DS, as well as extending benefits to the aging population at large.


Assuntos
Doença de Alzheimer , Prosencéfalo Basal , Síndrome de Down , Humanos , Animais , Camundongos , Idoso , Parvalbuminas , Neurônios GABAérgicos , Colina O-Acetiltransferase , Modelos Animais de Doenças , Degeneração Neural , Suplementos Nutricionais , Colina
13.
Artigo em Inglês | MEDLINE | ID: mdl-37844967

RESUMO

OBJECTIVE: To compare evaluations of depressive episodes and suggested treatment protocols generated by Chat Generative Pretrained Transformer (ChatGPT)-3 and ChatGPT-4 with the recommendations of primary care physicians. METHODS: Vignettes were input to the ChatGPT interface. These vignettes focused primarily on hypothetical patients with symptoms of depression during initial consultations. The creators of these vignettes meticulously designed eight distinct versions in which they systematically varied patient attributes (sex, socioeconomic status (blue collar worker or white collar worker) and depression severity (mild or severe)). Each variant was subsequently introduced into ChatGPT-3.5 and ChatGPT-4. Each vignette was repeated 10 times to ensure consistency and reliability of the ChatGPT responses. RESULTS: For mild depression, ChatGPT-3.5 and ChatGPT-4 recommended psychotherapy in 95.0% and 97.5% of cases, respectively. Primary care physicians, however, recommended psychotherapy in only 4.3% of cases. For severe cases, ChatGPT favoured an approach that combined psychotherapy, while primary care physicians recommended a combined approach. The pharmacological recommendations of ChatGPT-3.5 and ChatGPT-4 showed a preference for exclusive use of antidepressants (74% and 68%, respectively), in contrast with primary care physicians, who typically recommended a mix of antidepressants and anxiolytics/hypnotics (67.4%). Unlike primary care physicians, ChatGPT showed no gender or socioeconomic biases in its recommendations. CONCLUSION: ChatGPT-3.5 and ChatGPT-4 aligned well with accepted guidelines for managing mild and severe depression, without showing the gender or socioeconomic biases observed among primary care physicians. Despite the suggested potential benefit of using atificial intelligence (AI) chatbots like ChatGPT to enhance clinical decision making, further research is needed to refine AI recommendations for severe cases and to consider potential risks and ethical issues.


Assuntos
Ansiolíticos , Médicos de Atenção Primária , Humanos , Depressão/tratamento farmacológico , Reprodutibilidade dos Testes , Colina O-Acetiltransferase , Antidepressivos/uso terapêutico
14.
Neurobiol Dis ; 188: 106319, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37813167

RESUMO

Amongst other molecules, the cholinergic system consists of choline-acetyltransferase (ChAT, - synthesis enzyme), acetylcholinesterase (AChE - primary hydrolysis enzyme), and butyrylcholinesterase (BuChE - secondary hydrolysis enzyme). In the brainstem, the Dorsal Motor Nucleus of The Vagus (DMNV) has high cholinergic expression and is a region of interest in the neuropathology of sudden infant death syndrome (SIDS). SIDS is the unexpected death of a seemingly healthy infant, but postmortem brainstem abnormalities suggesting altered cholinergic regulation have been found. This study aimed to determine the percentage of positive ChAT and AChE neurons within the infant DMNV through immunohistochemistry at the three levels of the brainstem medulla (caudal, intermediate, and rostral), to investigate whether the proportion of neurons positive for these enzymes differs amongst the diagnostic subgroups of SIDS compared to those with an explained cause of Sudden unexpected death in infancy (eSUDI), and whether there were any associations with SIDS risk factors (male gender, cigarette smoke exposure, co-sleeping/bed sharing, and prone sleeping). Results showed that ChAT-positive neurons were lower in the rostral DMNV in the SIDS II cohort, and within the caudal and intermediate DMNV of infants who were exposed to cigarette smoke. These findings suggest altered cholinergic regulation in the brainstem of SIDS infants, with potential contribution of cigarette smoke exposure, presumably via the nicotinic acetylcholinergic receptor system.


Assuntos
Acetilcolinesterase , Morte Súbita do Lactente , Humanos , Lactente , Masculino , Butirilcolinesterase , Colina , Colina O-Acetiltransferase , Colinérgicos
15.
Inn Med (Heidelb) ; 64(11): 1058-1064, 2023 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-37843579

RESUMO

Artificial intelligence (AI)-based language models, such as ChatGPT offer an enormous potential for research and medical care but also for clinical workflow optimization by making medical documentation easier and more efficient in taking over standardized routine tasks. With their ability to guess a text's content using word statistics and thus outputting contextually relevant results in chat dialogues, large language models (LLM) can provide appropriate summaries of medical documentation for different target groups. For instance, text generation in easy to understand language could potentially contribute to an increase in patients' health literacy and, consequently, to increased adherence to treatment. Subsequent, the function of AI-based chatbot models to improve user experiences and enhance competence in the use of AI-based language models will be adressed. Current limitations and chances in creating epicrises are presented as an experience report. In the future, the implementation of local LLMs in medical management systems (hospital information systems, HIS and practice administration systems, PAS) and in conjunction with the electronic patient records (ePA) can fundamentally change clinical and outpatient care.


Assuntos
Inteligência Artificial , Registros Eletrônicos de Saúde , Humanos , Assistência Ambulatorial , Colina O-Acetiltransferase , Idioma
16.
Nutrients ; 15(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37686777

RESUMO

BACKGROUND: Sedentary behavior may affect the types of food consumed in children and adolescents' daily diets. Previous published studies are limited to local surveys. This study aimed to explore the relationship between sedentary behavior and food intake among children and adolescents. METHODS: A stratified sampling technique was employed in the present cross-sectional study. Demographic characteristics, sedentary behavior, transportation modes, and food intake were investigated. RESULTS: We found that children and adolescents who watched movies or TV programs online or on their smartphones on weekends and who chatted online on weekends, including on QQ (an instant messaging software service) and WeChat (an instant messaging software service), increased their intake of instant noodles and fried pasta (Spearman's rho = 0.468, 0.575, 0.465, and 0.323; p < 0.05). Children and adolescents who chatted online on weekends, including on QQ and WeChat, increased their intake of tofu skin (Spearman's rho = 0.461; p < 0.05), and those who browsed online on weekdays increased their intake of whole-fat liquid milk (Spearman's rho = 0.455; p < 0.05). Children and adolescents who browsed and chatted online on weekends, including on QQ and WeChat, and who played computer or smartphone games, increased their intake of fried potato chips (French fries or other fried snacks) (Spearman's rho = 0.568, 0.270, and 0.412; p < 0.05). With respect to modes of transportation used to travel to and from school, children and adolescents who took buses and subways increased their intake of rice, instant noodles, sweet potatoes, soybean milk, tofu skin, processed meat products (sausage, ham sausage, or lunch meat), fish, shrimp, vegetables, nuts, and sweet cookies (buns, cakes, Dim sum, and moon cakes) (Spearman's rho = 0.394, 0.536, 0.630, 0.408, 0.485, 0.441,0.410, 0.424, 0.444, 0.541, and 0.366; p < 0.05). CONCLUSIONS: Sedentary behavior affects the types of food consumed in children and adolescents' daily diets. Children and adolescents who browsed online on weekdays increased their intake of whole-fat liquid milk, but also increased their intake of foods with high fat, high salt, and low nutrient density. Children and adolescents taking buses and subways increased their intake of low-nutrition quality products. Public awareness efforts should focus on reducing the consumption of low-nutrition quality products and nutritional education.


Assuntos
Alimentos Marinhos , Verduras , Animais , Estudos Transversais , China , Colina O-Acetiltransferase , Ingestão de Alimentos
17.
Sci Rep ; 13(1): 12299, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516800

RESUMO

Pharyngeal muscle activity and responsiveness are key pathophysiological traits in human obstructive sleep apnea (OSA) and strong contributors to improvements with pharmacotherapy. The thyrotropin-releasing hormone (TRH) analog taltirelin is of high pre-clinical interest given its neuronal-stimulant properties, minimal endocrine activity, tongue muscle activation following microperfusion into the hypoglossal motor nucleus (HMN) or systemic delivery, and high TRH receptor expression at the HMN compared to rest of the brain. Here we test the hypothesis that taltirelin increases HMN activity and/or responsivity to excitatory stimuli applied across sleep-wake states in-vivo. To target hypoglossal motoneurons with simultaneous pharmacological and optical stimuli we used customized "opto-dialysis" probes and chronically implanted them in mice expressing a light sensitive cation channel exclusively on cholinergic neurons (ChAT-ChR2, n = 12) and wild-type mice lacking the opsin (n = 10). Both optical stimuli applied across a range of powers (P < 0.001) and microperfusion of taltirelin into the HMN (P < 0.020) increased tongue motor activity in sleeping ChAT-ChR2 mice. Notably, taltirelin increased tonic background tongue motor activity (P < 0.001) but not responsivity to excitatory optical stimuli across sleep-wake states (P > 0.098). This differential effect on tonic motor activity versus responsivity informs human studies of the potential beneficial effects of taltirelin on pharyngeal motor control and OSA pharmacotherapy.


Assuntos
Diálise Renal , Apneia Obstrutiva do Sono , Humanos , Animais , Camundongos , Neurônios Motores , Sono , Cafeína , Colina O-Acetiltransferase , Niacinamida , Atividade Motora
18.
Sci Rep ; 13(1): 9463, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301897

RESUMO

The memory-type control charts, such as cumulative sum (CUSUM) and exponentially weighted moving average control chart, are more desirable for detecting a small or moderate shift in the production process of a location parameter. In this article, a novel Bayesian adaptive EWMA (AEWMA) control chat utilizing ranked set sampling (RSS) designs is proposed under two different loss functions, i.e., square error loss function (SELF) and linex loss function (LLF), and with informative prior distribution to monitor the mean shift of the normally distributed process. The extensive Monte Carlo simulation method is used to check the performance of the suggested Bayesian-AEWMA control chart using RSS schemes. The effectiveness of the proposed AEWMA control chart is evaluated through the average run length (ARL) and standard deviation of run length (SDRL). The results indicate that the proposed Bayesian control chart applying RSS schemes is more sensitive in detecting mean shifts than the existing Bayesian AEWAM control chart based on simple random sampling (SRS). Finally, to demonstrate the effectiveness of the proposed Bayesian-AEWMA control chart under different RSS schemes, we present a numerical example involving the hard-bake process in semiconductor fabrication. Our results show that the Bayesian-AEWMA control chart using RSS schemes outperforms the EWMA and AEWMA control charts utilizing the Bayesian approach under simple random sampling in detecting out-of-control signals.


Assuntos
Colina O-Acetiltransferase , Projetos de Pesquisa , Teorema de Bayes , Simulação por Computador , Método de Monte Carlo
19.
Int J Mol Sci ; 24(10)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37240261

RESUMO

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer's disease and Lewy body dementia.


Assuntos
Fator de Crescimento Neural , Neuropeptídeos , Camundongos , Animais , Fator de Crescimento Neural/metabolismo , Neuropeptídeos/metabolismo , Hipocampo/metabolismo , Colinérgicos/metabolismo , Colina O-Acetiltransferase/genética , Colina O-Acetiltransferase/metabolismo
20.
Sci Rep ; 13(1): 4569, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024502

RESUMO

ChatGPT is not only fun to chat with, but it also searches information, answers questions, and gives advice. With consistent moral advice, it can improve the moral judgment and decisions of users. Unfortunately, ChatGPT's advice is not consistent. Nonetheless, it does influence users' moral judgment, we find in an experiment, even if they know they are advised by a chatting bot, and they underestimate how much they are influenced. Thus, ChatGPT corrupts rather than improves its users' moral judgment. While these findings call for better design of ChatGPT and similar bots, we also propose training to improve users' digital literacy as a remedy. Transparency, however, is not sufficient to enable the responsible use of AI.


Assuntos
Julgamento , Princípios Morais , Software , Alfabetização , Colina O-Acetiltransferase
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