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Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of neurotransmitters released to mediate cell-cell communication which are essential to brain functions in health and disease. We hypothesized that SZ may involve dysregulation of neurotransmitters secreted from neurons. To gain an understanding of human SZ, induced neurons (iNs) were derived from SZ patients and healthy control subjects to investigate peptide neurotransmitters, known as neuropeptides, which represent the major class of transmitters. The iNs were subjected to depolarization by high KCl in the culture medium and the secreted neuropeptides were identified and quantitated by nano-LC-MS/MS tandem mass spectrometry. Several neuropeptides were identified from schizophrenia patient-derived neurons, including chromogranin B (CHGB), neurotensin, and natriuretic peptide. Focusing on the main secreted CHGB neuropeptides, results revealed differences in SZ iNs compared to control iN neurons. Lower numbers of distinct CHGB peptides were found in the SZ secretion media compared to controls. Mapping of the peptides to the CHGB precursor revealed peptides unique to either SZ or control, and peptides common to both conditions. Also, the iNs secreted neuropeptides under both KCl and basal (no KCl) conditions. These findings are consistent with reports that chromogranin B levels are reduced in the cerebrospinal fluid and specific brain regions of SZ patients. These findings suggest that iNs derived from SZ patients can model the decreased CHGB neuropeptides observed in human SZ.
Assuntos
Cromogranina B , Neurônios , Neuropeptídeos , Neurotransmissores , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Neuropeptídeos/metabolismo , Neurônios/metabolismo , Cromogranina B/metabolismo , Masculino , Neurotransmissores/metabolismo , Feminino , Espectrometria de Massas em Tandem/métodos , Adulto , Pessoa de Meia-Idade , Neurotensina/metabolismo , Células Cultivadas , Encéfalo/metabolismoRESUMO
OBJECTIVES: Wax typodonts are widely used as pre-clinical teaching tools to test and research the complex force systems created by archwire activations, however, a limitation is the inability to quantify the resultant statically indeterminate tooth movements. The aim of this study was to develop an analogue-to-digital typodont system to quantify the effects of archwire activations on individual typodont teeth in three dimensions. METHODS: The typodont system was developed using CAD/CAM technology. Posterior expansion, squared, tapered, asymmetrical arch forms and reversed curve of Spee activations were tested with three repeats. The resulting three-dimensional movements of individual typodont teeth were assessed with six degrees of freedom (df). Cartesian coordinate systems were set for each tooth. Mesio-distal, bucco-lingual and intrusive-extrusive movements were assessed as changes in the location of the geometrically estimated centre of resistance in the x, y and z axes, respectively. Torque, tip and rotation movements were assessed as the rotations around the mesio-distal, bucco-lingual and intrusive-extrusive axes, respectively. RESULTS: Individual typodont tooth displacements from each activation could reliably be described with six df. The transversal-to-sagittal movement ratio ranged from 2:1 to 7:1, depending on the activation. Asymmetrical arch form activations caused a midline shift and affected the lateral overjet. Reversing the curve of Spee led to intrusion of incisors and second molars, extrusion of premolars and first molars and pronounced first and third order effects. CONCLUSION: The digital typodont system is a promising teaching tool. The tested activations have implications in three dimensions, which should be considered when planning tooth movements.
Assuntos
Má Oclusão , Humanos , Dente Molar , Dente Pré-Molar , Incisivo , Técnicas de Movimentação Dentária/métodosRESUMO
BACKGROUND: An effective tooth brushing technique is essential in maintaining oral hygiene, especially for patients wearing fixed orthodontic appliances. Traditional tooth brushing techniques are mainly designed for the general population without orthodontic appliances, which may not account for the oral condition of orthodontic patients due to the increased biofilm formation. The aim of this study was to design an orthodontic tooth brushing technique and compare its effectiveness with the traditional modified Bass technique. METHODS: Sixty patients wearing fixed orthodontic appliances were included in this two-arm paralleling randomized controlled trial. Thirty patients were assigned to the modified Bass technique group and 30 patients were assigned to the orthodontic tooth brushing technique group. The orthodontic tooth brushing technique involved a biting motion on the head of toothbrush in order to place the toothbrush bristles behind the archwires and around the brackets. Plaque index (PI) and gingival index (GI) were used to assess oral hygiene. Outcome measurements were taken at baseline and 1 month after the intervention. RESULTS: The new orthodontic tooth brushing technique significantly reduced PI (average PI reduction = 0.42 ± 0.13), especially in the gingival (0.53 ± 0.15) and interproximal (0.52 ± 0.18) areas (p < 0.05 for all). No significant reduction was found for the GI (p > 0.05 for all). CONCLUSION: The new orthodontic tooth brushing technique showed a promising result in reducing PI in patients wearing fixed orthodontic appliances.
Assuntos
Placa Dentária , Higiene Bucal , Humanos , Escovação Dentária , Placa Dentária/prevenção & controle , Índice de Placa Dentária , Aparelhos Ortodônticos Fixos , Aparelhos OrtodônticosRESUMO
The strategic redesign of microbial biosynthetic pathways is a compelling route to access molecules of diverse structure and function in a potentially environmentally sustainable fashion. The promise of this approach hinges on an improved understanding of acyl carrier proteins (ACPs), which serve as central hubs in biosynthetic pathways. These small, flexible proteins mediate the transport of molecular building blocks and intermediates to enzymatic partners that extend and tailor the growing natural products. Past combinatorial biosynthesis efforts have failed due to incompatible ACP-enzyme pairings. Herein, we report the design of chimeric ACPs with features of the actinorhodin polyketide synthase ACP (ACT) and of the Escherichia coli fatty acid synthase (FAS) ACP (AcpP). We evaluate the ability of the chimeric ACPs to interact with the E. coli FAS ketosynthase FabF, which represents an interaction essential to building the carbon backbone of the synthase molecular output. Given that AcpP interacts with FabF but ACT does not, we sought to exchange modular features of ACT with AcpP to confer functionality with FabF. The interactions of chimeric ACPs with FabF were interrogated using sedimentation velocity experiments, surface plasmon resonance analyses, mechanism-based cross-linking assays, and molecular dynamics simulations. Results suggest that the residues guiding AcpP-FabF compatibility and ACT-FabF incompatibility may reside in the loop I, α-helix II region. These findings can inform the development of strategic secondary element swaps that expand the enzyme compatibility of ACPs across systems and therefore represent a critical step toward the strategic engineering of "un-natural" natural products.
Assuntos
Proteína de Transporte de Acila/metabolismo , Proteínas de Escherichia coli/metabolismo , Ácido Graxo Sintases/metabolismo , Policetídeo Sintases/metabolismo , Proteína de Transporte de Acila/química , Sequência de Aminoácidos , Quimera/metabolismo , Escherichia coli/enzimologia , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Ácido Graxo Sintase Tipo II/metabolismo , Ácido Graxo Sintases/química , Ácidos Graxos/metabolismo , Simulação de Dinâmica Molecular , Policetídeo Sintases/química , Policetídeos/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismoRESUMO
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer's disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid ß and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor-dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter-dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Astrócitos , Glucose , Glicólise , Hipocampo , Indolamina-Pirrol 2,3,-Dioxigenase , Cinurenina , Neurônios , Animais , Humanos , Masculino , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Astrócitos/metabolismo , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Hipocampo/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/metabolismo , Ácido Láctico/metabolismo , Potenciação de Longa Duração , Memória/efeitos dos fármacos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neurônios/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Proteínas tau/metabolismo , Triptofano/metabolismoRESUMO
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer Disease (AD), and recent proteomic studies highlight a disruption of glial carbohydrate metabolism with disease progression. Here, we report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN) in the first step of the kynurenine pathway, rescues hippocampal memory function and plasticity in preclinical models of amyloid and tau pathology by restoring astrocytic metabolic support of neurons. Activation of IDO1 in astrocytes by amyloid-beta 42 and tau oligomers, two major pathological effectors in AD, increases KYN and suppresses glycolysis in an AhR-dependent manner. Conversely, pharmacological IDO1 inhibition restores glycolysis and lactate production. In amyloid-producing APP Swe -PS1 ΔE9 and 5XFAD mice and in tau-producing P301S mice, IDO1 inhibition restores spatial memory and improves hippocampal glucose metabolism by metabolomic and MALDI-MS analyses. IDO1 blockade also rescues hippocampal long-term potentiation (LTP) in a monocarboxylate transporter (MCT)-dependent manner, suggesting that IDO1 activity disrupts astrocytic metabolic support of neurons. Indeed, in vitro mass-labeling of human astrocytes demonstrates that IDO1 regulates astrocyte generation of lactate that is then taken up by human neurons. In co-cultures of astrocytes and neurons derived from AD subjects, deficient astrocyte lactate transfer to neurons was corrected by IDO1 inhibition, resulting in improved neuronal glucose metabolism. Thus, IDO1 activity disrupts astrocytic metabolic support of neurons across both amyloid and tau pathologies and in a model of AD iPSC-derived neurons. These findings also suggest that IDO1 inhibitors developed for adjunctive therapy in cancer could be repurposed for treatment of amyloid- and tau-mediated neurodegenerative diseases.
RESUMO
OBJECTIVES: This study aimed to obtain a consensus agreement from an expert panel on the metaverse for exercise rehabilitation in stroke patients using the Delphi technique. METHODS: This study recruited twenty-two experts and conducted three rounds of online surveys between January and February 2023. The Delphi consensus technique was performed online to review and evaluate the framework module. A panel of experts, including scholars, physicians, physical therapists, and physical education specialists in the Republic of Korea, was invited to participate in this study. For each round, the expert consensus was defined as more than 90% of the expert panel agreeing or strongly agreeing with the proposed items. RESULTS: A total of twenty experts completed the three Delphi rounds. First, virtual reality-assisted (VR) treadmill walking could improve cognitive function, concentration, muscular endurance, stroke prevention, proper weight maintenance, and cardiorespiratory function. Second, related technology, safety, price, place, and securing experts would be obstacles or challenges in VR-assisted treadmill walking for stroke patients. Third, the role of exercise instructors in exercise planning, performance, and assessment for VR-assisted treadmill walking is equally important, and reeducation for them is required. Fourth, VR-assisted treadmill walking for stroke patients requires an exercise intensity of at least five times a week, about one hour each time. CONCLUSIONS: This study showed that the metaverse for exercise rehabilitation for stroke patients could be successfully developed and would be feasible to be implemented in the future. However, it would have limitations in terms of technology, safety, price, place, and expert factors to be overcome in the future.
Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Técnica Delphi , Terapia por Exercício/métodos , Previsões , CaminhadaRESUMO
Introduction: Healthcare for the aging population has become a crucial issue in South Korea to maintain the elderly's quality of life, and physical activity is of primary importance for older adults. This study evaluated the exercise characteristics and satisfaction of the elderly who participated in physical activity programs provided by senior welfare centers in South Korea. Methods: We surveyed 266 participants to learn the characteristics of the elderly's exercise participation and their satisfaction with instructors, exercise programs, and facilities provided by senior welfare centers. A total of 263 copies were analyzed using the SPSS 23.0 statistical software. Results and discussion: The top three physical activity programs that the elderly participated in senior welfare centers were dancing (25.3%), gymnastics (24.8%), and table tennis/badminton (13.2%). There were significant differences in respondents' satisfaction according to sex, education level, spouse, family type, and monthly income per household (p < 0.05). The elderly were satisfied with programs (4.183 ± 0.483), facilities (3.881 ± 0.483), and instructors (3.604 ± 0.483) in order. Also, this study shows that user satisfaction differs depending on the demographic characteristics (gender, education, marital status, family type, economic status) and the characteristics of the exercise participation of the elderly (exercise duration, participation period). Conclusions: In conclusion, we presented the elderly's satisfaction with physical activity programs in senior welfare centers, suggesting that the elderly need physical activity programs according to their demographic and exercise characteristics.
Assuntos
Satisfação Pessoal , Qualidade de Vida , Humanos , Idoso , Envelhecimento , Exercício Físico , Fatores SocioeconômicosRESUMO
BACKGROUND: COVID-19 has become a significant healthcare issue, particularly challenging for patients with ankylosing spondylitis (AS), because immune-related diseases and their treatments could adversely affect the susceptibility to or severity of a viral infection. OBJECTIVE: This study is conducted to present an exercise rehabilitation program that patients older than 60 years with AS can do at home during the COVID-19 pandemic. METHODS: Three Delphi surveys were conducted to reach a consensus on home-based rehabilitation programs. This study recruited ten experts and performed three Delphi rounds for a month. RESULTS: The expert panel suggested that home-based rehabilitation for the patients should be carried out with a clear rehabilitation goal. Their final recommendations are to institute a program aimed to ease symptoms, such as pain and stiffness; encourage patients to consult with experts regularly to ensure that they perform exercise rehabilitation properly at home; add fast walking and stretching to the rehabilitation program; and see if indoor cycling, Pilates, or yoga could be appropriate. CONCLUSIONS: This study suggests that patients with AS over 60 should repeat low-intensity exercises, such as stretching, for an hour a day, four to six times a week during the COVID-19 pandemic.
Assuntos
COVID-19 , Espondilite Anquilosante , Exercício Físico , Terapia por Exercício , Humanos , Pandemias , Espondilite Anquilosante/diagnóstico , Resultado do TratamentoRESUMO
Forces and moments delivered by a straight wire connecting two orthodontic brackets are statically indeterminate and cannot be estimated using the classical equations of static equilibrium. To identify the mechanics of such two-bracket systems, Burstone and Koenig used the principles of linear beam theory to estimate the resulting force systems. In the original publication, however, it remains unclear how the force systems were calculated because no reference or computational details on the underlying principles have been provided. Using the moment carry-over principle and the relative angulation of the brackets, a formula was derived to calculate the relative moments of the two brackets. Because of the moment equilibrium, the vertical forces that exist as a forcecouple on the two brackets can also be calculated. The accuracy of the proposed approach can be validated using previously published empirical data.
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OBJECTIVE: To assess the immediate response of lips in three dimensions (3D) resulting from simulated maxillary incisor advancement. MATERIALS AND METHODS: Incremental maxillary incisor advancement was simulated by placing wax of increasing thickness (+2 mm, +4 mm, +6 mm) on the incisors of 20 participants, and the induced lip changes were recorded using 3D stereophotogrammetry. The induced displacement of lip landmarks was quantified using 3D image analysis software. Data were analyzed using a repeated-measures analysis of variance (ANOVA) after adjusting for age and sex of the study participants. RESULTS: A large interindividual variation in lip response to simulated incisor advancement was observed. A significant overall effect on 3D lip changes was found for increasing values of simulated incisor advancement (F = 13.2; P < .001) as well as significant differences between anatomical landmarks of the lip (F = 7.4; P < .01). Most points moved outward and anterosuperiorly, except the midpoint and corners of the lip. Greatest movement was observed in the sagittal plane, followed by the vertical and transverse planes. CONCLUSIONS: Maxillary incisor advancement significantly affects upper lip change in three planes of space: particularly the anteroposterior plane, in which the response to simulated advancement appears to be nonlinear.