Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 421
Filtrar
1.
Neural Regen Res ; 20(3): 811-812, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886950
2.
Disabil Rehabil ; : 1-6, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39282857

RESUMEN

PURPOSE: This position paper aims to: (1) summarise the current state of the Australian disability support sector and its need to advance training practices that enhance empathetic behaviours; (2) Highlight how virtual reality technology is currently being deployed in training in the sector; and (3) highlight challenges that may arise from a lack of user acceptance testing and user experience design considerations, and why future studies are needed to explore these factors. BACKGROUND: The disability support industry has responded to new market demands for DSWs to provide quality supports that take a client-centred approach. To achieve this, some disability service providers have turned to virtual reality. POSITION: Due to factors such as limited user acceptance testing, lack of user experience design practices, such undertakings may prove to be an expensive and ineffective exercise. Future studies should focus on ways to increase the sector's acceptance of virtual reality interventions. Design considerations need to ensure the product is intuitive, easy to learn, and able to be used as intended. CONCLUSION: Future design considerations include, (1) their level of technical literacy, (2) their attitude and perception of technology, and (3) how to communicate the onboarding message and incorporate a co-design approach.


Rethink research and co-design considerations aimed at disability support worker virtual reality training interventionsConsider the disability support sector's technical literacy level during design stagesAssess the disability support sector's attitude and perception of technologyExplore how to best communicate the onboarding message to win over disability support workers to use new technology through a co-design approach.

3.
Platelets ; 35(1): 2389967, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39169763

RESUMEN

The impact of the biophysical environment on the platelet storage lesion (PSL) has mainly focused on reduced temperature storage, overlooking the significance of storage-induced shear stress. Shear stress in platelet storage refers to the frictional force acting parallel to the bag surface and exists solely through the implementation of agitation. This study investigates whether minimizing exposure to agitation-induced shear stress can alleviate the unexplained loss of function in stored platelet concentrates for neonatal transfusion (neonatal PCs). Using particle tracking analysis, fluid motion was measured in neonatal and adult platelet storage bags under agitation frequencies ranging from 20-60 rpm. Platelets stored at 20-60 rpm agitation over 8 days were examined by biochemical analysis, aggregation, and expression of activation markers. Results indicate that neonatal PCs experience significantly higher storage-induced shear stress compared to adult doses, leading to reduced functionality and increased activation from day 2 of storage. Adjusting the neonatal PC agitation frequency to 20 rpm improved functionality in early storage, while 40 rpm maintains this improvement throughout storage with reduced activation, compared to 60 rpm storage. This study confirms that small volume PC storage for neonatal use contributes to the PSL through the induction of shear stress, suggesting further evaluation of the recommended agitation frequency for neonatal PCs or postponement of the production of neonatal PCs until requested for neonatal transfusion.


Context Approximately 1­5% of all neonates and up to 50% of critically ill newborns, present with low platelet counts, and will require platelet transfusion support.Platelet concentrates stored for neonatal transfusion have previously shown an accelerated reduction in quality during storage compared to platelet concentrates stored for adult transfusion and therefore may not provide as effective a therapeutic product.The current study hypothesized this loss of function over storage (known as the platelet storage lesion) to be a result of shear stress induced by agitation, exacerbated by the use of smaller bags in the neonatal preparation.Findings Our findings show that storage of platelet concentrates as smaller bags suitable for neonatal transfusion accelerates the platelet storage lesion, which experience a 4-fold greater shear stress than the adult preparation.The shear stress experienced by platelet concentrates stored for neonatal transfusion could be reduced by reducing the speed of agitation, thereby reducing the extent of the platelet storage lesion.Impact This study provides evidence that small volume storage promotes shear stress in platelet concentrates stored for neonatal transfusion, and optimizing storage conditions to reduce the shear stress induced by agitation can help to offset the platelet storage lesion.Further evaluation is required to establish a recommended agitation frequency for platelet concentrates stored for neonatal transfusion. An alternative strategy might include postponement of the production of platelet concentrates for neonatal transfusion until a neonatal transfusion is requested.


Asunto(s)
Plaquetas , Conservación de la Sangre , Humanos , Plaquetas/metabolismo , Recién Nacido , Conservación de la Sangre/métodos , Transfusión de Plaquetas/métodos , Adulto
4.
J Speech Lang Hear Res ; 67(9): 2977-2986, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39173051

RESUMEN

PURPOSE: The purpose of this study was to investigate the relationship between perceptual ratings of hypernasality made during connected speech and velopharyngeal (VP) gap size measured in millimeters in the sagittal plane during sustained vowel production using magnetic resonance imaging (MRI). METHOD: A retrospective cross-sectional analysis was completed. A subgroup of 110 participants from another study with an Mage of 10.1 years presenting for management of VP insufficiency was included. Perceptual ratings of hypernasality during connected speech and measurement of gap size during sustained /i/ production on MRI were performed by raters blinded to the participants' medical and surgical history. RESULTS: There was a moderate-to-strong, positive correlation (r = .61; p < .001) between hypernasality ratings and VP gap size measured on MRI using sustained /i/. The odds of a higher hypernasality rating increased as the gap size increased (odds ratio = 1.34; 95% CI [1.20, 1.49]; p < .001). The predicted probability for hypernasality ratings of none/minimal/mild steadily decreased as the gap size increased indicating that lower ratings of hypernasality were associated with smaller gap sizes. For the rating of "moderate" hypernasality, the predicted probability of the rating steadily increased up to 8 mm and then decreased as the gap size continued to increase. The predicted probability for a hypernasality rating of "severe" consistently increased as the gap size increased. CONCLUSIONS: Hypernasality ratings made at the connected speech level were significantly associated with VP gap size as measured during sustained vowel production. These findings suggest sustained vowel production elicited on MRI may adequately characterize VP gap size in the evaluation of VP insufficiency.


Asunto(s)
Imagen por Resonancia Magnética , Insuficiencia Velofaríngea , Humanos , Femenino , Masculino , Estudios Retrospectivos , Estudios Transversales , Insuficiencia Velofaríngea/fisiopatología , Niño , Habla/fisiología , Adolescente , Medición de la Producción del Habla , Trastornos de la Voz/fisiopatología , Percepción del Habla/fisiología , Fonética , Adulto Joven
5.
BMJ Open ; 14(8): e087918, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39181556

RESUMEN

INTRODUCTION: Inequities in COVID-19 infection and vaccine uptake among historically marginalised racial and ethnic groups in the USA persist. Individuals with rheumatic conditions, especially those who are immunocompromised, are especially vulnerable to severe infection, with significant racialised inequities in infection outcomes and in vaccine uptake. Structural racism, historical injustices and misinformation engender racial and ethnic inequities in vaccine uptake. The Popular Opinion Lleader (POL) model, a community-based intervention that trains trusted community leaders to disseminate health information to their social network members (eg, friends, family and neighbours), has been shown to reduce stigma and improve care-seeking behaviours. METHODS AND ANALYSIS: This is a community-based cluster randomised controlled trial led by a team of community and academic partners to compare the efficacy of training POLs with rheumatic or musculoskeletal conditions using a curriculum embedded with a racial justice vs a biomedical framework to increase COVID-19 vaccine uptake and reduce vaccine hesitancy. This trial began recruitment in February 2024 in Boston, Massachusetts and Chicago, Illinois, USA. Eligible POLs are English-speaking adults who identify as Black and/or of African descent, have a diagnosis of a rheumatic or musculoskeletal condition and have received >=1 COVID-19 vaccine after 31 August 2022. POLs will be randomised to a 6-module virtual educational training; the COVID-19 and vaccine-related content will be the same for both groups however the framing for arm 1 will be with a racial justice lens and for arm 2, a biomedical preventative care-focused lens. Following the training, POLs will disseminate the information they learned to 12-16 social network members who have not received the most recent COVID-19 vaccine, over 4 weeks. The trial's primary outcome is social network member COVID-19 vaccine uptake, which will be compared between intervention arms. ETHICS AND DISSEMINATION: This trial has ethical approval in the USA. This has been approved by the Mass General Brigham Institutional Review Board (IRB, 2023P000686), the Northwestern University IRB (STU00219053), the Boston University/Boston Medical Center IRB (H-43857) and the Boston Children's Hospital IRB (P00045404). Results will be published in a publicly accessible peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05822219.


Asunto(s)
Negro o Afroamericano , Vacunas contra la COVID-19 , COVID-19 , Difusión de la Información , Enfermedades Reumáticas , Adulto , Femenino , Humanos , Masculino , Boston , Chicago , COVID-19/prevención & control , Difusión de la Información/métodos , Aceptación de la Atención de Salud/etnología , Enfermedades Reumáticas/complicaciones , Vacilación a la Vacunación
7.
Cleft Palate Craniofac J ; : 10556656241271666, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136069

RESUMEN

INTRODUCTION: The levator veli palatini (LVP) muscle has two segments with distinct roles in velopharyngeal function. Previous research suggests longer extravelar segments with shorter intravelar segments may lead to a more advantageous mechanism for velopharyngeal closure. The purpose of this study was to examine whether the distribution of the LVP intravelar and extravelar segments differs between children with cleft palate with and without VPI and controls. METHODS: The study included 97 children: 37 with cleft palate +/- lip with VPI, 37 controls, and 19 with cleft palate with normal resonance. Measures included mean LVP length, mean extravelar LVP length, and intravelar LVP length. RESULTS: Overall mean LVP length was similar (P = .267) between controls and children with cleft palate (with and without VPI). However, there was a significant difference (P < .001) between group for both intravelar and extravelar LVP lengths: the intravelar segment was significantly longer in those with VPI compared to controls and children with cleft palate and normal resonance; and the extravelar segment was significantly shorter in those with VPI compared to controls and children with cleft palate and normal resonance. CONCLUSIONS: Results from this study demonstrate a significant difference between the distribution of the functional segments of the LVP among children with VPI, with a more disadvantageous distribution of the muscle segments among those with VPI.

8.
J Evid Based Soc Work (2019) ; : 1-15, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39215471

RESUMEN

PURPOSE: The guiding documents of the social work profession establish social justice as central to the discipline and practice of social work, yet there is little consensus on the meaning of the term. Therefore, the goal of this study was to examine how faculty and staff in one school of social work defined social justice. METHODS: Data for this study were drawn from a school climate survey distributed within one school of social work with an explicitly stated commitment to social justice. Ninety-three staves and faculty responded to the open-ended question: How do you define social justice? FINDINGS: Three themes were identified in how participants defined social justice as a form of evidence-based meaning making: (1) equality, (2) equity, and (3) advocacy and action. DISCUSSION: We conclude this article by discussing implications for how social workers can incorporate a critical approach to defining social justice that extends beyond equality and equity. Specifically, we recommend that the profession work toward a common, evidenced-based understanding of social justice to effectively educate current and future social workers to dismantle systems of oppression at all levels of social work.

9.
Int J Mol Sci ; 25(14)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39062765

RESUMEN

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that is characterized by the infiltration of peripheral immune cells into the central nervous system (CNS), secretion of inflammatory factors, demyelination, and axonal degeneration. Inflammatory mediators such as cytokines alter cellular function and activate resident CNS cells, including astrocytes. Notably, interferon (IFN)γ is a prominent pleiotropic cytokine involved in MS that contributes to disease pathogenesis. Astrocytes are dynamic cells that respond to changes in the cellular microenvironment and are highly responsive to many cytokines, including IFNγ. Throughout the course of MS, intrinsic cell stress is initiated in response to inflammation, which can impact the pathology. It is known that cell stress is pronounced during MS; however, the specific mechanisms relating IFNγ signaling to cell stress responses in astrocytes are still under investigation. This review will highlight the current literature regarding the impact of IFNγ signaling alone and in combination with other immune mediators on astrocyte synthesis of free oxygen radicals and cell death, and cover what is understood regarding astrocytic mitochondrial dysfunction and endoplasmic reticulum stress.


Asunto(s)
Astrocitos , Estrés del Retículo Endoplásmico , Interferón gamma , Esclerosis Múltiple , Transducción de Señal , Humanos , Astrocitos/metabolismo , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Interferón gamma/metabolismo , Animales , Mitocondrias/metabolismo , Estrés Oxidativo
10.
bioRxiv ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39071355

RESUMEN

Astrocytic interferon (IFN)γ signaling is associated with a reduction in neuroinflammation. We have previously shown that the benefits of astrocytic IFNγ arise from a variety of mechanisms; however, downstream effectors responsible for regulating this protection are unknown. We address this by identifying a specific transcription factor that may play a key role in modulating the consequences of IFNγ signaling. RNA-sequencing of primary human astrocytes treated with IFNγ revealed basic leucine zipper ATF-like transcription factor ( BATF )2 as a highly expressed interferon-specific gene. Primarily studied in the periphery, BATF2 has been shown to exert both inflammatory and protective functions; however, its function in the central nervous system (CNS) is unknown. Here, we demonstrate that human spinal cord astrocytes upregulate BATF2 transcript and protein in an IFNγ-specific manner. Additionally, we found that BATF2 prevents overexpression of interferon regulatory factor (IRF)1 and IRF1 targets such as Caspase-1, which are known downstream pro-inflammatory mediators. We also show that Batf2 -/- mice exhibit exacerbated clinical disease severity in a murine model of CNS autoimmunity, characterized by an increase in both CNS immune cell infiltration and demyelination. Batf2 -/- mice also exhibit increased astrocyte-specific expression of IRF1 and Caspase-1, suggesting an amplified interferon response in vivo . Further, we demonstrate that BATF2 is expressed primarily in astrocytes in MS lesions and that this expression is co-localized with IRF1. Collectively, our results further support a protective role for IFNγ and implicate BATF2 as a key suppressor of overactive immune signaling in astrocytes during neuroinflammation.

11.
J Occup Environ Med ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955810

RESUMEN

OBJECTIVE: The cross-sectional study evaluates if the pre-pandemic work environments in nursing homes predict COVID-19 cases among residents and staff, accounting for other factors. METHOD: Leveraging data from a survey of California and Ohio nursing homes (n = 340), we examined if Workplace Integrated Safety and Health domains - Leadership, Participation, and Comprehensive and Collaborative strategies predicted cumulative COVID-19 cases among nursing home residents and staff. RESULTS: In Ohio, a 1-unit increase in Leadership score was associated with 2 fewer staff cases and 4 fewer resident cases. A 1-unit increase in Comprehensive and Collaborative Strategies score in California showed an average marginal effect of approximately 1 less staff case and 2 fewer resident cases. CONCLUSION: These findings suggest that leadership commitment and inter-department collaboration to prioritize worker safety, may have protected against COVID-19 cases in nursing homes.

12.
J Cutan Pathol ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38986680

RESUMEN

Posttransplantation primary cutaneous T-cell lymphomas (PT-CTCL) are a rare complication of sustained immunosuppression in the posttransplant setting. When present, PT-CTCLs are typically EBV- and exhibit features of mycosis fungoides/Sézary syndrome or CD30+ lymphoproliferative disorders. We present a case of a 75-year-old individual who developed skin lesions 30 years after liver transplantation. Pathologic evaluation of the skin biopsy revealed involvement by a clonal, EBV+ T-cell population of gamma/delta lineage with no evidence of systemic disease. Comprehensive genomic profiling was performed, confirming focal one-copy loss of 6q23.3, altogether consistent with the extremely rare and unusual diagnosis of primary cutaneous EBV+ extranodal NK/T-cell lymphoma of gamma/delta T-cell lineage in the posttransplantation setting.

13.
J Prim Care Community Health ; 15: 21501319241263223, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39077980

RESUMEN

BACKGROUND: Early detection of autism spectrum disorder (ASD) has the potential to significantly reduce the impact of the condition, however previous reviews have found little evidence to support screening programs for ASD in young children. METHODS: We conducted a review with the aim of updating evidence on 3 aspects: (a) diagnostic stability of ASD in young children; (b) accuracy of ASD screening tools in young children; and (c) the benefits of early interventions in screen-detected young children with ASD. RESULTS: A total of 33 studies were included in our review. Five studies looking at diagnostic stability reported estimates ranging from 71.9% to 100%, however the majority only included a follow-up of 24 months and all studies raised concerns regarding the risk of bias due particularly to lack of blinding, sample size, and patient flow. A total of 25 studies, reported in 26 articles, were identified that reported accuracy data on 11 screening tools. Most of the reports were concerned with versions of M-CHAT, reporting sensitivity estimates from 0.67 to 1.0; however, many of these were deemed to be of high risk of bias due to lack of blinding and follow-up. Four studies reported on early interventions in screen-detected children; however, the majority did not find significant improvements on the relevant outcomes. CONCLUSIONS: Overall, the evidence on screening for ASD in young children captured by this review is not conclusive regarding the 3 aspects of screening in this population. Future studies should attempt to ensure blinded diagnostic assessments, include longer follow-up periods and limit attrition.


Asunto(s)
Trastorno del Espectro Autista , Tamizaje Masivo , Humanos , Trastorno del Espectro Autista/diagnóstico , Preescolar , Tamizaje Masivo/métodos , Diagnóstico Precoz , Lactante , Niño
14.
Sci Rep ; 14(1): 16993, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043848

RESUMEN

The BCG vaccine is given to millions of children globally but efficacy wanes over time and differences in the immune systems between infants and adults can influence vaccine efficacy. To this end, 34 rhesus macaques were vaccinated with BCG within seven days of birth and blood samples were collected over 88 weeks for quantification of blood cell populations. Overall, the composition of cell populations did not change significantly between BCG vaccinated and unvaccinated groups, and that BCG vaccination did not perturb normal development. In comparison to adult macaques, higher numbers of CD4+ T-cells, Tregs and NK cells were measured in the infant age group, suggesting a potential bias towards immunosuppressive and innate immune populations. Antigen-specific IFNγ secreting cell frequencies in infant BCG vaccinated animals were detectable in peripheral blood samples for 36 weeks after vaccination but declined following this. To evaluate the long-term impact of infant BCG vaccination on subsequent revaccination with BCG, a pilot study of three adult macaques received an aerosol BCG revaccination approximately 3 years after their initial BCG vaccination as infants. This induced an increase in PPD-specific IFNγ secreting cells, and increased secretion of the cytokines IFNγ and IL-1ß, following stimulation with other microorganisms, which are signals associated with trained innate immunity.


Asunto(s)
Animales Recién Nacidos , Vacuna BCG , Inmunización Secundaria , Macaca mulatta , Macaca mulatta/inmunología , Vacuna BCG/inmunología , Animales Recién Nacidos/inmunología , Linfocitos/inmunología , Citocinas/sangre , Citocinas/inmunología , Animales , Masculino , Femenino
15.
Cleft Palate Craniofac J ; : 10556656241266365, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39056299

RESUMEN

OBJECTIVE: Compare the effectiveness of palatoplasty and pharyngoplasty procedures at resolving hypernasality in patients with 22q11.2 deletion syndrome (22q). DESIGN: Retrospective cohort study. SETTING: Metropolitan children's hospital. PATIENTS: Fourteen patients with 22q presenting for management of velopharyngeal insufficiency. INTERVENTIONS: Palatoplasty or pharyngoplasty procedure. MAIN OUTCOME MEASURE: Resolution of hypernasality 12 months postoperatively. RESULTS: Both procedure groups had a mean preoperative velopharyngeal gap of 6.2 mm during phonation. No patient who underwent palatoplasty achieved resolution of hypernasality; 1/7 patients had worse hypernasality, 4/7 had no change, and 2/7 had improved hypernasality. In contrast, hypernasality was resolved in 6/7 patients in the pharyngoplasty group, which was significantly (P = .03) higher than the palatoplasty group. CONCLUSIONS: In patients with 22q, palatoplasty procedures may be less effective than pharyngoplasty procedures at resolving hypernasality. This may be due to underlying anatomic or physiologic differences, such as increased pharyngeal depth and hypodynamic muscles.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39046401

RESUMEN

This case report describes a full-term infant with a cleft palate who experienced malnutrition because of the delayed introduction of a cleft-adapted bottle and identifies potential areas for improvement in clinical practice. The infant's weight for age z-score at birth was 0.05 and dropped to -1.45 by 2 months of age, indicating mild malnutrition. The infant established care with a cleft team and a cleft-adapted bottle was recommended as the primary feeding method. Feeding time subsequently decreased from 60 minutes per feeding to 20 minutes. The infant presented for palate repair at 9 months of age, and his z-score was -0.01, indicating he was no longer malnourished. Cleft-adapted bottles aid in feeding efficiency in infants with cleft palate, which may subsequently impact weight gain. Appropriate weight gain is essential to receive timely cleft palate repair and support healing.

17.
Cell Rep ; 43(7): 114373, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38900638

RESUMEN

Biomolecular condensates have emerged as major drivers of cellular organization. It remains largely unexplored, however, whether these condensates can impart mechanical function(s) to the cell. The heterochromatin protein HP1α (Swi6 in Schizosaccharomyces pombe) crosslinks histone H3K9 methylated nucleosomes and has been proposed to undergo condensation to drive the liquid-like clustering of heterochromatin domains. Here, we leverage the genetically tractable S. pombe model and a separation-of-function allele to elucidate a mechanical function imparted by Swi6 condensation. Using single-molecule imaging, force spectroscopy, and high-resolution live-cell imaging, we show that Swi6 is critical for nuclear resistance to external force. Strikingly, it is the condensed yet dynamic pool of Swi6, rather than the chromatin-bound molecules, that is essential to imparting mechanical stiffness. Our findings suggest that Swi6 condensates embedded in the chromatin meshwork establish the emergent mechanical behavior of the nucleus as a whole, revealing that biomolecular condensation can influence organelle and cell mechanics.


Asunto(s)
Núcleo Celular , Proteínas Cromosómicas no Histona , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Proteínas Cromosómicas no Histona/metabolismo , Núcleo Celular/metabolismo , Homólogo de la Proteína Chromobox 5 , Heterocromatina/metabolismo , Cromatina/metabolismo
18.
J Deaf Stud Deaf Educ ; 29(3): 436-437, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913496

Asunto(s)
Lectura , Humanos
19.
Eur J Med Chem ; 275: 116604, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38917665

RESUMEN

The endogenous opioid system regulates pain through local release of neuropeptides and modulation of their action on opioid receptors. However, the effect of opioid peptides, the enkephalins, is short-lived due to their rapid hydrolysis by enkephalin-degrading enzymes. In turn, an innovative approach to the management of pain would be to increase the local concentration and prolong the stability of enkephalins by preventing their inactivation by neural enkephalinases such as puromycin-sensitive aminopeptidase (PSA). Our previous structure-activity relationship studies offered the S-diphenylmethyl cysteinyl derivative of puromycin (20) as a nanomolar inhibitor of PSA. This chemical class, however, suffered from undesirable metabolism to nephrotoxic puromycin aminonucleoside (PAN). To prevent such toxicity, we designed and synthesized 5'-chloro substituted derivatives. The compounds retained the PSA inhibitory potency of the corresponding 5'-hydroxy analogs and had improved selectivity toward PSA. In vivo treatment with the lead compound 19 caused significantly reduced pain response in antinociception assays, alone and in combination with Met-enkephalin. The analgesic effect was reversed by the opioid antagonist naloxone, suggesting the involvement of opioid receptors. Further, PSA inhibition by compound 19 in brain slices caused local increase in endogenous enkephalin levels, corroborating our rationale. Pharmacokinetic assessment of compound 19 showed desirable plasma stability and identified the cysteinyl sulfur as the principal site of metabolic liability. We gained additional insight into inhibitor-PSA interactions by molecular modeling, which underscored the importance of bulky aromatic amino acid in puromycin scaffold. The results of this study strongly support our rationale for the development of PSA inhibitors for effective pain management.


Asunto(s)
Transducción de Señal , Animales , Relación Estructura-Actividad , Transducción de Señal/efectos de los fármacos , Masculino , Ratones , Estructura Molecular , Relación Dosis-Respuesta a Droga , Humanos , Antígenos CD13/antagonistas & inhibidores , Antígenos CD13/metabolismo , Encefalinas/química , Encefalinas/metabolismo , Encefalinas/farmacología , Puromicina/farmacología , Puromicina/metabolismo , Puromicina/química , Analgésicos/farmacología , Analgésicos/química , Aminopeptidasas/antagonistas & inhibidores , Aminopeptidasas/metabolismo , Ratas
20.
Sci Rep ; 14(1): 12635, 2024 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-38825652

RESUMEN

We describe an approach aimed at helping artificial intelligence develop theory of mind of their human teammates to support team interactions. We show how this can be supported through the provision of quantifiable, machine-readable, a priori information about the human team members to an agent. We first show how our profiling approach can capture individual team member characteristic profiles that can be constructed from sparse data and provided to agents to support the development of artificial theory of mind. We then show how it captures features of team composition that may influence team performance. We document this through an experiment examining factors influencing the performance of ad-hoc teams executing a complex team coordination task when paired with an artificial social intelligence (ASI) teammate. We report the relationship between the individual and team characteristics and measures related to task performance and self-reported perceptions of the ASI. The results show that individual and emergent team profiles were able to characterize features of the team that predicted behavior and explain differences in perceptions of ASI. Further, the features of these profiles may interact differently when teams work with human versus ASI advisors. Most strikingly, our analyses showed that ASI advisors had a strong positive impact on low potential teams such that they improved the performance of those teams across mission outcome measures. We discuss these findings in the context of developing intelligent technologies capable of social cognition and engage in collaborative behaviors that improve team effectiveness.


Asunto(s)
Inteligencia Artificial , Teoría de la Mente , Humanos , Masculino , Femenino , Conducta Cooperativa , Adulto , Análisis y Desempeño de Tareas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...