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1.
PLoS One ; 19(5): e0302524, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753728

RESUMEN

Acute behavioural disturbance (ABD), sometimes called 'excited delirium', is a medical emergency. In the UK, some patients presenting with ABD are managed by advanced paramedics (APs), however little is known about how APs make restraint decisions. The aim of this research is to explore the decisions made by APs when managing restraint in the context of ABD, in the UK pre-hospital ambulance setting. Seven semi-structured interviews were undertaken with APs. All participants were experienced APs with post-registration, post-graduate advanced practice education and qualifications. The resulting data were analysed using reflexive thematic analysis, informed by critical realism. We identified four interconnected themes from the interview data. Firstly, managing complexity and ambiguity in relation to identifying ABD patients and determining appropriate treatment plans. Secondly, feeling vulnerable to professional consequences from patients deteriorating whilst in the care of APs. Thirdly, negotiating with other professionals who have different roles and priorities. Finally, establishing primacy of care in relation to incidents which involve police officers and other professionals. A key influence was the need to characterise incidents as medical, as an enabler to establishing clinical leadership and decision-making control. APs focused on de-escalation techniques and sought to reduce physical restraint, intervening with pharmacological interventions if necessary to achieve this. The social relationships and interactions with patients and other professionals at the scene were key to success. Decisions are a source of anxiety, with fears of professional detriment accompanying poor patient outcomes. Our results indicate that APs would benefit from education and development specifically in relation to making ABD decisions, acknowledging the context of inter-professional relationships and the potential for competing and conflicting priorities. A focus on joint, high-fidelity training with the police may be a helpful intervention.


Asunto(s)
Ambulancias , Toma de Decisiones , Servicios Médicos de Urgencia , Investigación Cualitativa , Restricción Física , Humanos , Reino Unido , Masculino , Técnicos Medios en Salud/psicología , Femenino , Auxiliares de Urgencia/psicología , Auxiliares de Urgencia/educación , Adulto , Paramédico
2.
Curr Opin Insect Sci ; 59: 101082, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37419251

RESUMEN

Extracting spatial information from temporal stimulus patterns is essential for sensory perception (e.g. visual motion direction detection or concurrent sound segregation), but this process remains understudied in olfaction. Animals rely on olfaction to locate resources and dangers. In open environments, where odors are dispersed by turbulent wind, detection of wind direction seems crucial for odor source localization. However, recent studies showed that insects can extract spatial information from the odor stimulus itself, independently from sensing wind direction. This remarkable ability is achieved by detecting the fine-scale temporal pattern of odor encounters, which contains information about the location and size of an odor source, and the distance between different odor sources.


Asunto(s)
Insectos , Odorantes , Animales , Olfato , Viento
3.
J Exp Anal Behav ; 120(1): 3-5, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37350325

RESUMEN

Over the last 3 decades, the use and popularity of canid models for basic and applied behavioral research has grown dramatically, and for good reasons. Dogs are uniquely among the human world, living and working in our homes and places of employment while an even greater population lives on the outskirts of human life, scavenging and navigating the city life. This provides a rich continuum of environmental contexts for the canine experience, leading to some unique and even human-like behaviors in animals. The articles in this special issue provide additional insight into factors that influence canine welfare, methods for evaluating dogs' preferences and the reinforcing effectiveness of stimuli, trick learning and retention, concept learning, and scent detection performance under sparse reinforcement conditions. Here we provide an overview of these articles and their contribution to our understanding of canine behavior.


Asunto(s)
Cognición , Aprendizaje , Animales , Perros , Humanos , Refuerzo en Psicología , Odorantes , Empleo
4.
Front Pediatr ; 11: 1103094, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37090919

RESUMEN

Noninvasive cardiopulmonary exercise testing (CPET) provides the valuable capacity to analyze pulmonary gas exchange and cardiovascular responses that can be used to differentiate normal cardiopulmonary responses from abnormal. This case report highlights a proposed role for CPET in identifying potential cardiac pathologies in at-risk adolescents. An abnormal CPET response in an asymptomatic adolescent revealed a family history of early-age CAD. The significance of the abnormal CPET response was further supported by the presence of an elevated concentration of circulating high sensitivity C-reactive protein (hs-CRP). These findings emphasize the importance of a thorough clinical evaluation in at-risk adolescents, as CPET can aid in the early detection and management of cardiac pathologies, especially when combined with other relevant biomarkers such as plasma hs-CRP concentration, which can further suggest underlying pathology. Management considerations using serial CPET evaluations are recommended. Thus, CPET abnormalities combined with elevated hs-CRP should be taken seriously and provide justification for further evaluation and monitoring in adolescents at risk for cardiovascular disease.

5.
Cortex ; 161: 38-50, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36889039

RESUMEN

Corpus callosum dysgenesis is a congenital abnormality whereby the corpus callosum fails to develop normally, and has been associated with a range of neuropsychological outcomes. One specific finding in some individuals with corpus callosum dysgenesis is "congenital mirror movement disorder", which is the presence of involuntary movements on one side of the body that mimic voluntary movements of the other side. Mirror movements have also been associated with mutations in the deleted in colorectal carcinoma (DCC) gene. The current study aims to comprehensively document the neuropsychological outcomes and neuroanatomical mapping of a family (a mother, daughter and son) with known DCC mutations. All three family members experience mirror movements, and the son additionally has partial agenesis of the corpus callosum (pACC). All family members underwent extensive neuropsychological testing, spanning general intellectual functioning, memory, language, literacy, numeracy, psychomotor speed, visuospatial perception, praxis and motor functioning, executive functioning, attention, verbal/nonverbal fluency, and social cognition. The mother and daughter had impaired memory for faces, and reduced spontaneous speech, and the daughter demonstrated scattered impairments in attention and executive functioning, but their neuropsychological abilities were largely within normal limits. By contrast, the son showed areas of significant impairment across multiple domains including reduced psychomotor speed, fine motor dexterity and general intellectual functioning, and he was profoundly impaired across areas of executive functioning and attention. Reductions in his verbal/non-verbal fluency, with relatively intact core language, resembled dynamic frontal aphasia. His relative strengths included aspects of memory and he demonstrated largely sound theory of mind. Neuroimaging revealed an asymmetric sigmoid bundle in the son, connecting, via the callosal remnant, the left frontal cortex with contralateral parieto-occipital cortex. Overall, this study documents a range of neuropsychological and neuroanatomical outcomes within one family with DCC mutations and mirror movements, including one with more severe consequences and pACC.


Asunto(s)
Agenesia del Cuerpo Calloso , Trastornos del Movimiento , Femenino , Humanos , Masculino , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Agenesia del Cuerpo Calloso/genética , Agenesia del Cuerpo Calloso/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Receptor DCC/genética , Mutación/genética , Neuroimagen
6.
Br Paramed J ; 7(3): 8-14, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36531800

RESUMEN

Introduction: Pre-hospital clinicians can expect to encounter patients with agitation, including acute behavioural disturbance (ABD). These situations carry significant risk for patients and emergency medical services. Advanced paramedics within the London Ambulance Service (LAS) are frequently tasked to these incidents. At present, little evidence exists regarding clinical decision-making and management of this patient group. We sought to explore the demographics of patients presenting with potential ABD and quantify the degree of agitation, physical restraint, effectiveness of chemical sedation and any associated complications. Methods: A retrospective analysis of pre-hospital clinical records for patients coded with ABD and attended by LAS advanced paramedics between 1 October 2019 and 30 September 2020. Sedation assessment tool (SAT) scores were used as the primary outcome measure. Results: A total of 237 patient records were identified. Of the patients, 147 (62%) were physically restrained and 104 (44%) were chemically sedated. Sedation was more commonly administered where patients were exposed to physical restraint. High SAT scores were associated with the administration of sedative agents and at higher doses. Of patients undergoing sedation, 89 (85%) had a SAT score reduction of 2 points or a final score ≤ 0. The mean SAT score reduction was 2.72. Three cases of minor injury were reported following physical restraint. Conclusion: Advanced paramedics undertook sedation in less than half the cohort, suggesting that other strategies such as communication and positioning were utilised. Most patients were managed into a state between being restless and rousable, largely negating the need for ongoing physical restraint during hospital transfer. Appropriately trained advanced paramedics can utilise sedation safely and effectively in selected cases.

7.
Resusc Plus ; 12: 100333, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36425452

RESUMEN

Background: The aims of this study were to establish epidemiology, clinical management and outcomes in cases of adult out-of-hospital cardiac arrest complicated by hyperthermia attended by the London Ambulance Service NHS Trust between January 2018 and December 2019. Where evidence is available in relation to this sub-set of cardiac arrest patients it is generally limited to small case series and we therefore we sought to improve knowledge and target therapeutic interventions. Methods and results: Retrospective analysis of 253 cases was undertaken following abstraction from an established cardiac arrest database. Age ranged from 18-99 years with a median of 72 years (IQR 28) and 53.4% (n = 135) of patients were female. Overall thirty-day mortality was 94.5% (n = 239), with 48.2% (n = 122) of patients recognised life extinct in the out-of-hospital phase following termination of resuscitation. No significant differences in clinical characteristics stratified according to temperature group were identified. The presumed aetiology was infective in 62.8% (n = 159) of patients, and due to drug ingestion or heat illness in 7.5% (n = 19) and 2% (n = 5) respectively. In the remaining cases (27.7%, n = 70) it was not possible to determine the likely cause of the arrest. Conclusions: Previous research relating to cardiac arrest complicated by hyperthermia is limited to case reports and small case series, suggesting that the current study represents the most comprehensive analysis of this sub-group of out-of-hospital cardiac arrest patients currently available. Most cases were associated with evidence of infection compared with drug related aetiologies and heat illness. Where indicated, cooling was applied infrequently using inconsistent methods.

8.
J Breath Res ; 17(1)2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36260978

RESUMEN

Evaluations of dogs as lung cancer detectors using breath samples have produced a variety of results, some quite promising. Breath samples are typically collected onto a substrate and stored in a sealed container when not in use, but volatile compounds dissipate when the substrate is exposed during training and evaluation sessions. Collection of appropriate samples for training and testing dogs requires significant resources and strict control of recruitment and sample collection processes. Therefore, some researchers re-use samples while training dogs. No systematic evaluation of the effect of sample re-use on dogs' training performance has been conducted, so the influence of this potentially important training factor is not known. We trained seven dogs to indicate the presence of lung cancer positive breath samples using an automated apparatus. The samples were stored at -60 °C or -80 °C. Samples from 460 individuals who were classified as positive or negative for lung cancer were used for training samples. Individual samples were presented to dogs up to four times over a period of 2 years. As sample re-use increased, sensitivity declined (-6.65,p= < .001, 95% CI [-10.56, -2.76]), specificity increased (2.87,p= .036, 95% CI [.19, 5.55]), and the dogs' bias shifted in the direction of a negative indication bias (-.094,p= < .001, 95% CI [-.149, -.39]). However, there were no significant changes in the measure associated with the detectability of the target (-0.30,p= .285, 95% CI [-.087, .26]). All observed changes in performance across sample re-use were small. Therefore, these findings suggest that sample re-use may be appropriate for training, but additional research is required to determine which factors underly changes in performance as breath samples are re-used.


Asunto(s)
Pruebas Respiratorias , Neoplasias Pulmonares , Perros , Animales , Pruebas Respiratorias/métodos , Olfato , Perros de Trabajo , Neoplasias Pulmonares/diagnóstico , Manejo de Especímenes
9.
J Exp Anal Behav ; 118(2): 181-185, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36053848

RESUMEN

Though operant learning has been applied to socially significant animal behavior for many years, connections between these practical applications and the basic science that supports them have weakened over time. There is a need for replications and extensions of technologies derived from basic research to applied animal settings, and for practical questions to be taken back to the lab where they can be modeled and studied under controlled conditions before incorporating the results in applied behavior-change research and practice. This special issue highlights ways that behavior analysis can contribute to and support the development of evidence-based applications with animals. Articles in this issue provide context for the relationship between basic research and practice in animal behavior, apply basic principles to animal behavior practice, and investigate practical problems using basic research techniques. Each of these is important for a robust interchange between basic science and practice. Here we comment on the contributions of each article to the literature and identify directions for future research.


Asunto(s)
Conducta Animal , Aprendizaje , Animales , Proyectos de Investigación
10.
J Exp Anal Behav ; 118(3): 398-411, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36053851

RESUMEN

Equivalence classes are defined according to the substitutability, or functional similarity, of the stimuli within a stimulus class. Several studies have demonstrated that the degree of functional similarity between stimuli in a class is dependent, in part, upon the number of nodes (intervening stimuli) between the stimuli. Higher nodal number is related to lower functional similarity. This effect is referred to as "nodality." There are three key factors that have not been simultaneously controlled for in the relevant studies: priming effects, reinforcement during training, and multiple stimulus functions of stimuli (sample, comparison, or both). In the present experiment, controlling for these factors, two 6-member, 4-node equivalence classes were established, and a within-class preference assessment was used to evaluate nodality. Of 12 participants, five achieved criterion accuracy (90%) during testing. These participants demonstrated nodality, showing preference for stimuli that were nodally proximal to a sample in the preference test. When distal comparisons were chosen, participants took longer, on average, to make the selection compared to selections of proximal stimuli. These findings are consistent with earlier studies demonstrating nodality, which suggests that nodality is a robust phenomenon and not an artifact of the factors that were controlled for in the present study.


Asunto(s)
Aprendizaje Discriminativo , Refuerzo en Psicología , Humanos
11.
J Exp Anal Behav ; 118(3): 376-397, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36054301

RESUMEN

Differential reinforcement of alternative behavior (DRA) involves placing problem behavior under extinction and simultaneously reinforcing a desirable behavior. Recent research revealed that, as predicted by Behavioral Momentum Theory, DRA may also increase the persistence of the problem behavior. This research has also shown that a different approach to DRA, in which an alternative behavior is trained in a separate context from the target behavior, produces less persistence than the standard procedure. The research on this phenomenon, so far, assessed persistence using extinction as the disruptor. DRA, however, is often implemented under conditions in which extinction of the problem behavior is not feasible. This study evaluated persistence of problem behavior following same- and separate- context DRA training using an alternative disruptor, an additional source of reinforcement. Following a successful reproduction of a previous study of extinction as a disruptor but with domestic hens, this study produced similar findings using an additional source of reinforcement as the disruptor. These findings add to the evidence that alternative DRA arrangements may avoid the response-strengthening effects found with traditional DRA procedures. The findings also demonstrate that disruptors other than extinction can be used to investigate response persistence following DRA and other procedures.


Asunto(s)
Pollos , Extinción Psicológica , Animales , Femenino , Esquema de Refuerzo , Refuerzo en Psicología , Terapia Conductista/métodos
12.
Behav Processes ; 197: 104620, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35301067

RESUMEN

Resurgence refers to a behavioral process in which a recent response is extinguished (or reinforcement conditions worsen) and a previously extinguished response recurs. In previous research, resurgence has been reliably produced when the resurgence procedure is repeated. Changes in the degree of increase of the resurging response across iterations of the procedure have been inconsistent, however, with some studies showing increases and some showing no changes or decreases in resurgence magnitude. The present study examined the nature of resurgence across repeated iterations of the conventional resurgence procedure by exposing four pigeons to the resurgence procedure six times in succession. In the first condition of the resurgence procedure, pecks on one key (e.g., the left) were reinforced under a variable-interval (VI) 30-s schedule. In the second condition pecks on that key were extinguished, and pecks on another key (e.g., the right) were reinforced under the same schedule. In the final condition there were no programmed consequences for either response. Resurgence was observed in 21 of 24 opportunities (87.5%). Iteration-over-iteration increases in resurgence were observed in 15 of 20 opportunities (75.0%), and this increase was found to be statistically significant. These findings demonstrate that, under certain conditions, resurgence generally increases in magnitude with repeated exposure to the procedures that generate it.


Asunto(s)
Condicionamiento Operante , Extinción Psicológica , Animales , Columbidae , Condicionamiento Operante/fisiología , Extinción Psicológica/fisiología , Esquema de Refuerzo , Refuerzo en Psicología
13.
Perspect Behav Sci ; 44(2-3): 359-387, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34632282

RESUMEN

Perspective taking has been studied extensively using a wide variety of experimental tasks. The theoretical constructs that are used to develop these tasks and interpret the results obtained from them, most notably theory of mind (ToM), have conceptual shortcomings from a behavior-analytic perspective. The behavioral approach to conceptualizing and studying this class of behavior is parsimonious and pragmatic, but the body of relevant research is currently small. The prominent relational frame theory (RFT) approach to derived perspective taking asserts that "deictic framing" is a core component of this class of behavior, but this proposal also appears to be conceptually problematic. We suggest that in many cases perspective taking is problem solving; when successful, both classes of behavior involve the emission of context-appropriate precurrent behavior that facilitates the appropriate response (i.e., the "solution"). Conceptualizing perspective taking in this way appears to have many advantages, which we explore herein.

14.
ERJ Open Res ; 7(2)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34084784

RESUMEN

BACKGROUND: The difference in patient comfort with conscious sedation versus general anaesthesia for bronchoscopy has not been adequately assessed in a randomised trial. This study aimed to assess if patient comfort during bronchoscopy with conscious sedation is noninferior to general anaesthesia. METHODS: 96 subjects were randomised to receive conscious sedation or general anaesthesia for bronchoscopy. The primary outcome was subject comfort. Secondary outcomes included willingness to undergo a repeat procedure if necessary and level of sedation assessed clinically and by bispectral index (BIS) monitoring. RESULTS: There was no significant difference between subject comfort scores (difference -0.01, 95% CI -0.63-0.61 on a 10-point scale; p=0.97) or willingness to undergo a repeat procedure (97.7% versus 91.8%, 95% CI -4.8-15.5%; p=0.37). Deeper levels of sedation in the general anaesthesia cohort was confirmed with both clinical and BIS monitoring. There was no significant difference in diagnostic accuracy (conscious sedation 93.9%, 95% CI 80.4-98.3% versus general anaesthesia 86.5%, 95% CI 72.0-94.1%; p=0.43). There were more complications (29.6%, 95% CI 18.2-44.2% versus 6.1%, 95% CI 2.1-16.5%; p<0.01) in the general anaesthesia group. There was no relationship between high BIS scores and subject discomfort. BIS levels <40 during a procedure were associated with increased complications. CONCLUSION: Conscious sedation is not inferior to general anaesthesia in providing patient comfort during bronchoscopy, despite lighter sedation, and is associated with fewer complications and comparable diagnostic accuracy. BIS monitoring may have a role in preventing complications associated with deeper sedation.

15.
Elife ; 102021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33945466

RESUMEN

Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure. Remodelling of the interhemispheric fissure (IHF) provides a substrate for callosal axons to cross between hemispheres, and its failure is the main cause of complete CCD. However, it is unclear whether defects in this process could give rise to the heterogeneity of expressivity and phenotypes seen in human cases of CCD. We identify incomplete IHF remodelling as the key structural correlate for the range of callosal abnormalities in inbred and outcrossed BTBR mouse strains, as well as in humans with partial CCD. We identify an eight base-pair deletion in Draxin and misregulated astroglial and leptomeningeal proliferation as genetic and cellular factors for variable IHF remodelling and CCD in BTBR strains. These findings support a model where genetic events determine corpus callosum structure by influencing leptomeningeal-astroglial interactions at the IHF.


Asunto(s)
Agenesia del Cuerpo Calloso/genética , Cuerpo Calloso/fisiología , Regulación del Desarrollo de la Expresión Génica/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Adulto , Anciano , Agenesia del Cuerpo Calloso/patología , Animales , Estudios de Cohortes , Cuerpo Calloso/crecimiento & desarrollo , Cuerpo Calloso/patología , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Persona de Mediana Edad , Fenotipo , Adulto Joven
17.
Elife ; 102021 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-33871356

RESUMEN

The forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). Deleted in colorectal carcinoma (DCC) and netrin 1 (NTN1) are molecules that have an evolutionarily conserved function in commissural axon guidance. The CC and HC are absent in Dcc and Ntn1 knockout mice, while other commissures are only partially affected, suggesting an additional aetiology in forebrain commissure formation. Here, we find that these molecules play a critical role in regulating astroglial development and IHF remodelling during CC and HC formation. Human subjects with DCC mutations display disrupted IHF remodelling associated with CC and HC malformations. Thus, axon guidance molecules such as DCC and NTN1 first regulate the formation of a midline substrate for dorsal commissures prior to their role in regulating axonal growth and guidance across it.


Asunto(s)
Astrocitos/metabolismo , Cuerpo Calloso/metabolismo , Receptor DCC/metabolismo , Telencéfalo/metabolismo , Agenesia del Cuerpo Calloso/genética , Agenesia del Cuerpo Calloso/metabolismo , Agenesia del Cuerpo Calloso/patología , Animales , Células COS , Línea Celular Tumoral , Movimiento Celular , Forma de la Célula , Chlorocebus aethiops , Cuerpo Calloso/embriología , Receptor DCC/genética , Regulación del Desarrollo de la Expresión Génica , Genotipo , Edad Gestacional , Células HEK293 , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Morfogénesis , Mutación , Netrina-1/genética , Netrina-1/metabolismo , Fenotipo , Transducción de Señal , Telencéfalo/embriología
18.
Behav Processes ; 185: 104356, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33577832

RESUMEN

Researchers have employed a variety of laboratory analogues of cryptic prey detection and applied signal detection to study factors influencing learning and performance in these ethological and applied scenarios. However, these procedural analogues do not appear to map closely onto their "real-world" counterparts, particularly with respect to the role of the "yes" (i.e., "attack") response and the payoff for this response (or its absence) on signal-present and signal-absent trials. Using domestic hens, we developed a procedural analogue in which a "yes" response requires some time to emit; such responses were reinforced only in the presence of a signal. In Experiment 1, we evaluated the influence of the "yes" response requirement by manipulating the number of responses required to qualify as a "yes" response. As the "yes" response requirement was increased, bias toward responding "no" increased, revealing that this is a critical factor controlling accuracy in this procedure. In Experiment 2, we evaluated the influence of signal probability and reinforcement rate on signal detection accuracy and found that neither of these factors significantly influenced accuracy or bias. These findings suggest that this procedural analogue may represent a valuable alternative for studying behaviour in relevant signal detection scenarios.


Asunto(s)
Pollos , Columbidae , Animales , Femenino , Aprendizaje , Esquema de Refuerzo , Refuerzo en Psicología
19.
Nat Commun ; 12(1): 1159, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33608529

RESUMEN

Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. Here we report that neural fold elevation during mouse spinal neurulation is vulnerable to deletion of the VANGL planar cell polarity protein 2 (Vangl2) gene in as few as 16% of neuroepithelial cells. Vangl2-deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2-replete neighbours. This inhibition of apical constriction involves diminished myosin-II localisation on neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2-deleted neuroepithelial cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap localisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects.


Asunto(s)
Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Defectos del Tubo Neural/genética , Neurulación/genética , Neurulación/fisiología , Citoesqueleto de Actina/metabolismo , Animales , Polaridad Celular/fisiología , Modelos Animales de Enfermedad , Eliminación de Gen , Ratones , Morfogénesis/genética , Morfogénesis/fisiología , Mutación , Miosina Tipo II/metabolismo , Cresta Neural/metabolismo , Células Neuroepiteliales/metabolismo , Células Neuroepiteliales/patología , Transcriptoma
20.
Ann Am Thorac Soc ; 18(7): 1167-1174, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33465334

RESUMEN

Rationale: Obesity presents a mechanical load to the thorax, which could perturb the generation of minute ventilation (V̇e) during exercise. Because the respiratory effects of obesity are not homogenous among all individuals with obesity and obesity-related effects could vary depending on the magnitude of obesity, we hypothesized that the exercise ventilatory response (slope of the V̇e and carbon dioxide elimination [V̇co2] relationship) would manifest itself differently as the magnitude of obesity increases.Objectives: To investigate the V̇e/V̇co2 slope in an obese population that spanned across a wide body mass index (BMI) range.Methods: A total of 533 patients who presented to a surgical weight loss center for pre-bariatric surgery testing performed an incremental maximal cycling test and were studied retrospectively. The V̇e/V̇co2 slope was calculated up to the ventilatory threshold. Patients were examined in groups based on BMI (category 1: 30-39.9 kg/m2, category 2: 40-49.9 kg/m2, and category 3: ≥50 kg/m2). Because the respiratory effects of obesity could be sex and/or age specific, we further examined patients in groups by sex and age (younger: <50 yr and older: ≥50 yr). Differences in the V̇e/V̇co2 slope were then compared between BMI category, age, and sex using a three-way ANOVA.Results: No significant BMI category by sex by age interactions was detected (P = 0.75). The V̇e/V̇co2 slope decreased with increases in BMI (category 1, 29.1 ± 4.0; category 2, 28.4 ± 4.1; and category 3, 27.1 ± 3.3) and was elevated in women (28.9 ± 4.1) compared with men (26.7 ± 3.2) (BMI category by sex interaction, P < 0.05). No age-related differences were observed (BMI category by age interaction, P = 0.55). The partial pressure for end-tidal CO2 was elevated at the ventilatory threshold in BMI category 3 compared with BMI categories 1 and 2 (both P < 0.01).Conclusions: These findings suggest that obesity presents a unique challenge to augmenting ventilatory output relative to CO2 elimination, such that the increase in the exercise ventilatory response becomes blunted as the magnitude of obesity increases. Further studies are required to investigate the clinical consequences and the mechanisms that may explain the attenuation of exercise ventilatory response with increasing BMI in men and women with obesity.


Asunto(s)
Insuficiencia Cardíaca , Consumo de Oxígeno , Dióxido de Carbono , Ejercicio Físico , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Obesidad , Estudios Retrospectivos
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