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1.
Artículo en Inglés | MEDLINE | ID: mdl-38653937

RESUMEN

In many everyday decisions, individuals choose between trialling something novel or something they know well. Deciding when to try a new option or stick with an option that is already known to you, known as the "explore/exploit" dilemma, is an important feature of cognition that characterises a range of decision-making contexts encountered by humans. Recent evidence has suggested preferences in explore/exploit biases are associated with psychopathology, although this has typically been examined within individual disorders. The current review examined whether explore/exploit decision-making represents a promising transdiagnostic target for psychosis, depression, and anxiety. A systematic search of academic databases was conducted, yielding a total of 29 studies. Studies examining psychosis were mostly consistent in showing that individuals with psychosis explored more compared with individuals without psychosis. The literature on anxiety and depression was more heterogenous; some studies found that anxiety and depression were associated with more exploration, whereas other studies demonstrated reduced exploration in anxiety and depression. However, examining a subset of studies that employed case-control methods, there was some evidence that both anxiety and depression also were associated with increased exploration. Due to the heterogeneity across the literature, we suggest that there is insufficient evidence to conclude whether explore/exploit decision-making is a transdiagnostic target for psychosis, depression, and anxiety. However, alongside our advisory groups of lived experience advisors, we suggest that this context of decision-making is a promising candidate that merits further investigation using well-powered, longitudinal designs. Such work also should examine whether biases in explore/exploit choices are amenable to intervention.

2.
J Appl Physiol (1985) ; 136(6): 1364-1375, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38572540

RESUMEN

Cold exposure increases blood pressure (BP) and salivary flow rate (SFR). Increased cold-induced SFR would be hypothesized to enhance oral nitrate delivery for reduction to nitrite by oral anaerobes and to subsequently elevate plasma [nitrite] and nitric oxide bioavailability. We tested the hypothesis that dietary nitrate supplementation would increase plasma [nitrite] and lower BP to a greater extent in cool compared with normothermic conditions. Twelve males attended the laboratory on four occasions. Baseline measurements were completed at 28°C. Subsequently, participants ingested 140 mL of concentrated nitrate-rich (BR; ∼13 mmol nitrate) or nitrate-depleted (PL) beetroot juice. Measurements were repeated over 3 h at either 28°C (Norm) or 20°C (Cool). Mean skin temperature was lowered compared with baseline in PL-Cool and BR-Cool. SFR was greater in BR-Norm, PL-Cool, and BR-Cool than PL-Norm. Plasma [nitrite] at 3 h was higher in BR-Cool (592 ± 239 nM) versus BR-Norm (410 ± 195 nM). Systolic BP (SBP) at 3 h was not different between PL-Norm (117 ± 6 mmHg) and BR-Norm (113 ± 9 mmHg). SBP increased above baseline at 1, 2, and 3 h in PL-Cool but not BR-Cool. These results suggest that BR consumption is more effective at increasing plasma [nitrite] in cool compared with normothermic conditions and blunts the rise in BP following acute cool air exposure, which might have implications for attenuating the increased cardiovascular strain in the cold.NEW & NOTEWORTHY Compared with normothermic conditions, acute nitrate ingestion increased plasma [nitrite], a substrate for oxygen-independent nitric oxide generation, to a greater extent during cool air exposure. Systolic blood pressure was increased during cool air exposure in the placebo condition with this cool-induced blood pressure increase attenuated after acute nitrate ingestion. These findings improve our understanding of environmental factors that influence nitrate metabolism and the efficacy of nitrate supplementation to lower blood pressure.


Asunto(s)
Presión Sanguínea , Frío , Estudios Cruzados , Nitratos , Humanos , Masculino , Nitratos/administración & dosificación , Nitratos/sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Método Doble Ciego , Adulto , Adulto Joven , Nitritos/sangre , Óxido Nítrico/metabolismo , Suplementos Dietéticos , Beta vulgaris , Temperatura Cutánea/efectos de los fármacos , Temperatura Cutánea/fisiología , Jugos de Frutas y Vegetales
3.
Trials ; 25(1): 143, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395922

RESUMEN

BACKGROUND: Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the 'Building Resilience through Socioemotional Training' (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology. METHODS: A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12-14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention. DISCUSSION: This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people's emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence. TRIAL REGISTRATION: ISRCTN88585916. Trial registration date: 20/04/2023.


Asunto(s)
Trastornos Mentales , Resiliencia Psicológica , Humanos , Adolescente , Emociones , Instituciones Académicas , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
BJPsych Open ; 9(5): e161, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37641851

RESUMEN

BACKGROUND: The ability to communicate is integral to all human relationships. Previous research has specifically highlighted communication within families as both a risk and protective factor for anxiety disorders and/or depression. Yet, there is limited understanding about whether communication is amenable to intervention in the context of adolescent psychopathology, and whether doing so improves outcomes. AIMS: The aim of this systematic review was to determine in which contexts and for whom does addressing communication in families appear to work, not work and why? METHOD: We pre-registered our systematic review with PROSPERO (identifier CRD42022298719), followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance and assessed study quality with the Risk of Bias 2 tool. RESULTS: Seven randomised controlled trials were identified from a systematic search of the literature. There was significant heterogeneity in the features of communication that were measured across these studies. There were mixed findings regarding whether family-focused interventions led to improvements in communication. Although there was limited evidence that family-focused interventions led to improvements in communication relative to interventions without a family-focused component, we discuss these findings in the context of the significant limitations in the studies reviewed. CONCLUSIONS: We conclude that further research is required to assess the efficacy of family-focused interventions for improving communication in the context of anxiety and depression in those aged 14-24 years.

5.
Trends Cogn Sci ; 27(11): 1085-1098, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37500422

RESUMEN

Patch foraging is a near-ubiquitous behaviour across the animal kingdom and characterises many decision-making domains encountered by humans. We review how a disposition to explore in adolescence may reflect the evolutionary conditions under which hunter-gatherers foraged for resources. We propose that neurocomputational mechanisms responsible for reward processing, learning, and cognitive control facilitate the transition from exploratory strategies in adolescence to exploitative strategies in adulthood - where individuals capitalise on known resources. This developmental transition may be disrupted by psychopathology, as there is emerging evidence of biases in explore/exploit choices in mental health problems. Explore/exploit choices may be an informative marker for mental health across development and future research should consider this feature of decision-making as a target for clinical intervention.

6.
PLoS One ; 18(5): e0283254, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37167208

RESUMEN

Although the COVID-19 pandemic has impacted the psychological wellbeing of some people, there is evidence that many have been much less affected. The Ecological Model of Resilience (EMR) may explain why some individuals are not resilient whilst others are. In this study we test the EMR in a comparison of UK survey data collected from the COVID-19 Psychological Research Consortium (C19PRC) longitudinal study of a representative sample of the United Kingdom (UK) adult population and data from an Italian arm of the study. We first compare data from the third wave of the UK arm of the study, collected in July/August 2020, with data from an equivalent sample and stage of the pandemic in Italy in July 2020. Next, using UK longitudinal data collected from C19PRC Waves 1, 3 and 5, collected between March 2020 and April 2021 we identify the proportion of people who were resilient. Finally, we examine which factors, drawn from the EMR, predict resilient and non-resilient outcomes. We find that the 72% of the UK sample was resilient, in line with the Italian study. In the cross-sectional logistic regression model, age and self-esteem were significantly associated with resilience whilst death anxiety thoughts, neuroticism, loneliness, and Post Traumatic Stress Disorder (PTSD) symptoms related to COVID-19 were significantly associated with Non-Resilient outcomes. In the longitudinal UK analysis, at Wave 5, 80% of the sample was Resilient. Service use, belonging to wider neighbourhood, self-rated health, self-esteem, openness, and externally generated death anxiety were associated with Resilient outcomes. In contrast, PTSD symptoms and loneliness were associated with Non-Resilient outcomes. The EMR effectively explained the results. There were some variables which are amenable to intervention which could increase resilience in the face of similar future challenges.


Asunto(s)
COVID-19 , Adulto , Humanos , COVID-19/epidemiología , Estudios Transversales , Estudios Longitudinales , Pandemias , Reino Unido/epidemiología
7.
Nitric Oxide ; 134-135: 10-16, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36889537

RESUMEN

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.


Asunto(s)
Beta vulgaris , Nitratos , Adulto Joven , Humanos , Líquido Extracelular , Dióxido de Nitrógeno , Presión Sanguínea , Nitritos , Suplementos Dietéticos , Soluciones para Diálisis/farmacología , Estudios Cruzados , Método Doble Ciego
9.
Ergonomics ; 66(10): 1449-1464, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36445933

RESUMEN

The clothing fabric and skin interact continuously across the many regions of users' bodies during wear, which can lead to both physical skin damage and discomfort. Therefore, this investigation aimed to explore the regional differences in skin friction, tactile perception, and sensitivity in both females and males during the skin-textile interaction. The static and dynamic friction coefficient and textile perception (texture, stickiness, pleasantness, and discomfort) were measured across the 36 selected testing body areas by using a friction measurement device. The results revealed there was a significant difference in skin friction, tactile perceptions, and sensitivity across the various body regions. The anterior neck had the highest skin friction in both females and males, and participants generally rated higher texture perception in their anterior aspects compared to posterior and lateral regions. There was no significant difference in skin friction, tactile perception ratings, and sensitivity between females and males. Practitioner summary: This study sought to examine regional variations in skin friction, tactile perception, and sensitivity during the skin-textile interaction. There was a significant difference in skin friction, tactile perceptions, and sensitivity across the various body regions and no significant sex effect on skin friction, tactile perception ratings, and sensitivity.


Asunto(s)
Piel , Percepción del Tacto , Masculino , Femenino , Humanos , Fricción , Tacto , Textiles
10.
Am J Physiol Regul Integr Comp Physiol ; 324(1): R102-R108, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36440900

RESUMEN

This investigation assessed the physiological effects of voluntary suppression of shivering thermogenesis in response to whole body cooling. Eleven healthy volunteers underwent passive air cooling (10°C), across three visits: NO_SUP, where participants allowed their body to freely regulate against the cold; FULL_SUP, where participants constantly suppressed shivering; INT_SUP, where participants intermittently suppressed shivering (5 min phases), interspersed with 5 min free regulation. Shivering was assessed via electromyography (EMG), mechanomyography (MMG), and whole body oxygen uptake (V̇o2), whereas body temperature and heat exchange were assessed via skin temperature, rectal temperature, and heat flux sensors. A 29% increase was observed in shivering onset time in the FULL_SUP trial compared with NO_SUP (P = 0.032). Assessing shivering intensity, EMG activity decreased by 29% (P = 0.034), MMG activity decreased by 35% (P = 0.031), whereas no difference was observed in V̇o2 (P = 0.091) in the FULL_SUP trial compared with NO_SUP. Partitioning the no-suppression and suppression phases of the INT_SUP trial, acute voluntary suppression significantly decreased V̇o2 (P = 0.001), EMG (P < 0.001), and MMG (P = 0.012) activity compared with the no-suppression phases. Shivering activity was restored in the no-suppression phases, equivalent to that in the NO_SUP trial (P > 0.3). No difference was observed in thermal metrics between conditions up to 60 min (P > 0.4). Humans can both constantly and periodically suppress shivering activity, leading to a delay in shivering onset and a reduction in shivering intensity. Following suppression, regular shivering is resumed.


Asunto(s)
Frío , Tiritona , Humanos , Tiritona/fisiología , Termogénesis/fisiología , Temperatura Corporal/fisiología , Temperatura Cutánea , Regulación de la Temperatura Corporal/fisiología
11.
J Appl Physiol (1985) ; 133(2): 247-261, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35652831

RESUMEN

The present research describes the development and validation of a cardiovascular model (CVR Model) for use in conjunction with advanced thermophysiological models, where usually only a total cardiac output is estimated. The CVR Model detailed herein estimates cardio-dynamic parameters (changes in cardiac output, stroke volume, and heart rate), regional blood flow, and muscle oxygen extraction, in response to rest and physical workloads, across a range of ages and aerobic fitness levels, as well as during exposure to heat, dehydration, and altitude. The model development strategy was to first establish basic resting and exercise predictions for cardio-dynamic parameters in an "ideal" environment (cool, sea level, and hydrated person). This basic model was then advanced for increasing levels of altitude, heat strain, and dehydration, using meta-analysis and reaggregation of published data. Using the estimated altitude- and heat-induced changes in maximum oxygen extraction and maximum cardiac output, the decline in maximum oxygen consumption at high altitude and in the heat was also modeled. A validation of predicted cardiovascular strain using heart rate was conducted using a dataset of 101 heterogeneous individuals (1,371 data points) during rest and exercise in the heat and at altitude, demonstrating that the CVR Model performs well (R2 = 0.82-0.84) in predicting cardiovascular strain, particularly at a group mean level (R2 = 0.97). The development of the CVR Model is aimed at providing the Fiala thermal Physiology & Comfort (FPC) Model and other complex thermophysiological models with improved estimations of cardiac strain and exercise tolerance, across a range of individuals during acute exposure to environmental stressors.NEW & NOTEWORTHY The present research promotes the adaption of thermophysiological modeling to the estimation of cardiovascular strain in individuals exercising under acute environmental stress. Integration with advanced models of human thermoregulation opens doors for detailed numerical analysis of athletes' performance and physiology during exercise, occupational safety, and individual work tolerability. The research provides a simple-to-validate metric of cardiovascular function (heart rate), as well as a method to evaluate key principles influencing exercise- and thermoregulation in humans.


Asunto(s)
Deshidratación , Ejercicio Físico , Gasto Cardíaco/fisiología , Ejercicio Físico/fisiología , Humanos , Modelos Teóricos , Oxígeno
12.
Int J Methods Psychiatr Res ; 31(4): e1928, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35759532

RESUMEN

OBJECTIVES: The COVID-19 Psychological Research Consortium (C19PRC) Study was established in March 2020 to monitor the psychological and socio-economic impact of the pandemic in the UK and other countries. This paper describes the protocol for Wave 5 (March-April 2021). METHODS: The survey assessed: COVID-19 related experiences; experiences of common mental health disorders; psychological characteristics; and social and political attitudes. Adults who participated in any previous wave (N = 4949) were re-invited to participate. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was nationally representative in terms of gender, age, and household income, amongst other factors. RESULTS: Overall, 2520 adults participated. A total of 2377 adults who participated in the previous survey wave (November-December 2020) were re-interviewed at Wave 5 (61.5% retention rate). Attrition between these two waves was predicted by younger age, lower household income, children living in the household, and treatment for mental health difficulties. Of the adults recruited into the C19PRC study at baseline, 57.4% (N = 1162) participated in Wave 5. The raking procedure re-balanced the longitudinal panel to within 1.5% of population estimates for selected socio-demographic characteristics. CONCLUSION: This paper outlines the growing strength of the publicly available C19PRC Study data for COVID-19-related interdisciplinary research.


Asunto(s)
COVID-19 , Adulto , Niño , Humanos , COVID-19/epidemiología , Pandemias , Salud Mental , Factores Socioeconómicos , Reino Unido/epidemiología
13.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-35046026

RESUMEN

Adverse childhood experiences (ACEs) are extreme stressors that lead to negative psychosocial outcomes in adulthood. Nonhuman animals explore less after exposure to early stress. Therefore, in this preregistered study, we hypothesized that reduced exploration following ACEs would also be evident in human adults. Further, we predicted that adults with ACEs, in a foraging task, would adopt a decision-making policy that relies on the most-recent reward feedback, a rational strategy for unstable environments. We analyzed data from 145 adult participants, 47 with four or more ACEs and 98 with fewer than four ACEs. In the foraging task, participants evaluated the trade-off between exploiting a known patch with diminishing rewards and exploring a novel one with a fresh distribution of rewards. Using computational modeling, we quantified the degree to which participants' decisions weighted recent feedback. As predicted, participants with ACEs explored less. However, contrary to our hypothesis, they underweighted recent feedback. These unexpected findings indicate that early adversity may dampen reward sensitivity. Our results may help to identify cognitive mechanisms that link childhood trauma to the onset of psychopathology.


Asunto(s)
Experiencias Adversas de la Infancia/psicología , Conducta Exploratoria , Retroalimentación , Recompensa , Algoritmos , Análisis de Varianza , Humanos , Modelos Psicológicos
14.
Int J Methods Psychiatr Res ; 31(1): e1899, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34739156

RESUMEN

OBJECTIVES: This paper outlines fieldwork procedures for Wave 4 of the COVID-19 Psychological Research Consortium (C19PRC) Study in the UK during November-December 2020. METHODS: Respondents provided data on socio-political attitudes, beliefs, and behaviours, and mental health disorders (anxiety, depression, and posttraumatic stress). In Phase 1, adults (N = 2878) were reinvited to participate. At Phase 2, new recruitment: (i) replenished the longitudinal strand to account for attrition; and (ii) oversampled from the devolved UK nations to facilitate robust between-country analyses for core study outcomes. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was representative of the baseline sample characteristics. RESULTS: In Phase 1, 1796 adults were successfully recontacted and provided full interviews at Wave 4 (62.4% retention rate). In Phase 2, 292 new respondents were recruited to replenish the panel, as well as 1779 adults from Wales, Scotland, and Northern Ireland, who were representative of the socio-political composition of the adult populations in these nations. The raking procedure successfully re-balanced the longitudinal panel to within 1% of population estimates for selected socio-demographic characteristics. CONCLUSION: The C19PRC Study offers a unique opportunity to facilitate and stimulate interdisciplinary research addressing important public health questions relating to the COVID-19 pandemic.


Asunto(s)
COVID-19 , Adulto , Ansiedad , Humanos , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios
15.
Temperature (Austin) ; 8(4): 306-319, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34901315

RESUMEN

The assessment of human internal/core temperature (T core) is relevant in many scientific disciplines, but also for public health authorities when attempting to identify individuals with fever. Direct assessment of T core is often invasive, impractical on a large scale, and typically requires close contact between the observer and the target subject. Non-contact infrared thermometry (NCIT) represents a practical solution in which T core can potentially be assessed from a safe distance and in mass screening scenarios, by measuring skin temperature at specific anatomical locations. However, the COVID-19 pandemic has clearly demonstrated that these devices are not being used correctly, despite expert guided specifications available in International Standard Organization (ISO) documents. In this review, we provide an overview of the most pertinent factors that should be considered by users of NCIT. This includes the most pertinent methodological and physiological factors, as well as an overview on the ability of NCIT to track human T core. For practical use, we provide a checklist based on relevant ISO standards which are simple to follow and should be consulted prior to using NCIT for assessment of human T core. Our intention is for users of NCIT to adopt this checklist, which may improve the performance of NCIT for its ability to track T core.

16.
Front Psychol ; 12: 787496, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34956012

RESUMEN

Humans exposed to hypoxia are susceptible to physiological and psychological impairment. Music has ergogenic effects through enhancing psychological factors such as mood, emotion, and cognition. This study aimed to investigate music as a tool for mitigating the performance decrements observed in hypoxia. Thirteen males (mean ± SD; 24 ± 4 years) completed one familiarization session and four experimental trials; (1) normoxia (sea level, 0.209 FiO2) and no music; (2) normoxia (0.209 FiO2) with music; (3) normobaric hypoxia (∼3800 m, 0.13 FiO2) and no music; and (4) normobaric hypoxia (0.13 FiO2) with music. Experimental trials were completed at 21°C with 50% relative humidity. Music was self-selected prior to the familiarization session. Each experimental trial included a 15-min time trial on an arm bike, followed by a 60-s isometric maximal voluntary contraction (MVC) of the biceps brachii. Supramaximal nerve stimulation quantified central and peripheral fatigue with voluntary activation (VA%) calculated using the doublet interpolation method. Average power output (W) was reduced with a main effect of hypoxia (p = 0.02) and significantly increased with a main effect of music (p = 0.001). When combined the interaction was additive (p = 0.87). Average MVC force (N) was reduced in hypoxia (p = 0.03) but VA% of the biceps brachii was increased with music (p = 0.02). Music reduced subjective scores of mental effort, breathing discomfort, and arm discomfort in hypoxia (p < 0.001). Music increased maximal physical exertion through enhancing neural drive and diminishing detrimental mental processes, enhancing performance in normoxia (6.3%) and hypoxia (6.4%).

17.
Cell Rep Med ; 2(10): 100422, 2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34755134

RESUMEN

Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRß), with subnanomolar affinity for the vitamin folic acid (FA), is upregulated during immune activation in hematopoietic cells of the myeloid lineage. This phenomenon has inspired a strong interest in exploring FRß-directed diagnostics/therapeutics. Previously, we have reported that FA-targeted aminopterin (AMT) therapy can modulate macrophage function and effectively treat animal models of inflammation. Our current investigation of a lead compound (EC2319) leads to discovery of a highly FR-specific mechanism of action independent of the root causes against inflammatory monocytes. We further show that EC2319 suppresses interleukin-6/interleukin-1ß release by FRß+ monocytes in a triple co-culture leukemic model of cytokine release syndrome with anti-CD19 chimeric antigen receptor T cells. Because of its chemical stability and metabolically activated linker, EC2319 demonstrates favorable pharmacokinetic characteristics and cross-species translatability to support future pre-clinical and clinical development.


Asunto(s)
Aminopterina/farmacología , Síndrome de Liberación de Citoquinas/prevención & control , Receptor 2 de Folato/genética , Antagonistas del Ácido Fólico/farmacología , Ácido Fólico/metabolismo , Macrófagos/efectos de los fármacos , Animales , Antígenos CD19/genética , Antígenos CD19/inmunología , Células CHO , Cricetulus , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/patología , Femenino , Receptor 1 de Folato/antagonistas & inhibidores , Receptor 1 de Folato/genética , Receptor 1 de Folato/inmunología , Receptor 2 de Folato/antagonistas & inhibidores , Receptor 2 de Folato/inmunología , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Ratones , Modelos Biológicos , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/patología , Células RAW 264.7 , Ratas , Ratas Endogámicas Lew , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/patología
18.
Sci Rep ; 11(1): 19237, 2021 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-34584175

RESUMEN

The COVID-19 pandemic has brought about unprecedented global changes in individual and collective behaviour. To reduce the spread of the virus, public health bodies have promoted social distancing measures while attempting to mitigate their mental health consequences. The current study aimed to identify cognitive predictors of social distancing adherence and mental health symptoms, using computational models derived from delay discounting (the preference for smaller, immediate rewards over larger, delayed rewards) and patch foraging (the ability to trade-off between exploiting a known resource and exploring an unknown one). In a representative sample of the UK population (N = 442), we find that steeper delay discounting predicted poorer adherence to social distancing measures and greater sensitivity to reward magnitude during delay discounting predicted higher levels of anxiety symptoms. Furthermore, under-valuing recently sampled information during foraging independently predicted greater violation of lockdown guidance. Our results suggest that those who show greater discounting of delayed rewards struggle to maintain social distancing. Further, those who adapt faster to new information are better equipped to change their behaviour in response to public health measures. These findings can inform interventions that seek to increase compliance with social distancing measures whilst minimising negative repercussions for mental health.


Asunto(s)
COVID-19/psicología , Adhesión a Directriz , Distanciamiento Físico , Ansiedad/epidemiología , Control de Enfermedades Transmisibles , Descuento por Demora , Femenino , Humanos , Masculino , Salud Mental , Motivación , Pandemias , Salud Pública , Reino Unido
19.
Physiol Meas ; 42(8)2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34320480

RESUMEN

Objective. To investigate the use of infrared thermography (IRT) for skin temperature measurement of moving athletes during competition and its sensitivity to factors that are traditionally standardised.Approach. Thermograms were collected for 18 female athletes during the 20 km racewalk at the 2019 World Athletics Championships, with a medium-wave, cooled indium antimonide medium wave infrared band (MWIR) and a long-wave, uncooled microbolometer longwave infrared band (LWIR) infrared camera.Main results. The MWIR provided greater clarity images of motion due to a shorter exposure and response time and produced a higher percentage of acceptable images. Analysing acceptable images only, the LWIR and WMIR produced good levels of agreement, with a bias of -0.1 ± 0.6 °C in mean skin temperature for the LWIR. As the surface area of an ROI was reduced, the measured temperature became less representative of the whole ROI. Compared to measuring the whole area ROI, a single central pixel produced a bias of 0.3 ± 0.3 °C (MWIR) and 0.1 ± 0.4 °C (LWIR) whilst using the maximum and minimum temperature pixels resulted in deviations of 1.3 ± 0.4 °C and -1.1 ± 0.3 °C (MWIR) and 1.2 ± 0.3 °C and -1.3 ± 0.4 °C (LWIR). The sensitivity to air and reflected temperatures was lower for the LWIR camera, due to the higher emissivity of skin in its wavelength.Significance. IRT provides an appropriate tool for the measurement of skin temperature during real-world competition and critically during athlete motion. The cheaper LWIR camera provides a feasible alternative to the MWIR in low rate of motion scenarios, with comparable precision and sensitivity to analysis. However, the LWIR is limited when higher speeds prevent the accurate measurement and ability to capture motion.


Asunto(s)
Temperatura Cutánea , Termografía , Atletas , Temperatura Corporal , Frío , Femenino , Humanos , Rayos Infrarrojos
20.
Eur J Appl Physiol ; 121(7): 1943-1954, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33765169

RESUMEN

PURPOSE: To assess five theoretical foundations underlying thermosensory testing using local thermal stimuli. METHODS: Thermal sensation, discomfort and the confidence of thermal sensation scores were measured in 9 female and 8 male volunteers in response to 17 physical contact temperature stimuli, ranging between 18-42 °C. These were applied to their dorsal forearm and lateral torso, across two sessions. RESULTS: Thermal sensation to physical temperature relationships followed a positive linear and sigmoidal fit at both forearm (r2 = 0.91/r2 = 0.91, respectively) and lateral torso (r2 = 0.90/ r2 = 0.91, respectively). Thermal discomfort to physical temperature relationships followed second and third-order fits at both forearm (r2 = 0.33/r2 = 0.34, respectively) and lateral torso (r2 = 0.38/r2 = 0.39, respectively) test sites. There were no sex-related or regional site differences in thermal sensation and discomfort across a wide range of physical contact temperatures. The median confidence of an individual's thermal sensation rating was measured at 86%. CONCLUSION: The relation between thermal sensation and physical contact temperature was well described by both linear and sigmoidal models, i.e., the distance between the thermal sensation anchors is close to equal in terms of physical temperatures changes for the range studied. Participants rated similar thermal discomfort level in both cold and hot thermal stimuli for a given increase or decrease in physical contact temperature or thermal sensation. The confidence of thermal sensation rating did not depend on physical contact temperature.


Asunto(s)
Temperatura Cutánea/fisiología , Sensación Térmica/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Adulto Joven
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