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1.
Nature ; 616(7957): 448-451, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36858072

RESUMEN

The Double Asteroid Redirection Test (DART) spacecraft successfully performed the first test of a kinetic impactor for asteroid deflection by impacting Dimorphos, the secondary of near-Earth binary asteroid (65803) Didymos, and changing the orbital period of Dimorphos. A change in orbital period of approximately 7 min was expected if the incident momentum from the DART spacecraft was directly transferred to the asteroid target in a perfectly inelastic collision1, but studies of the probable impact conditions and asteroid properties indicated that a considerable momentum enhancement (ß) was possible2,3. In the years before impact, we used lightcurve observations to accurately determine the pre-impact orbit parameters of Dimorphos with respect to Didymos4-6. Here we report the change in the orbital period of Dimorphos as a result of the DART kinetic impact to be -33.0 ± 1.0 (3σ) min. Using new Earth-based lightcurve and radar observations, two independent approaches determined identical values for the change in the orbital period. This large orbit period change suggests that ejecta contributed a substantial amount of momentum to the asteroid beyond what the DART spacecraft carried.

2.
Nature ; 616(7957): 452-456, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36858074

RESUMEN

Some active asteroids have been proposed to be formed as a result of impact events1. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA2, in addition to having successfully changed the orbital period of Dimorphos3, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions. Here we report the observations of the DART impact ejecta with the Hubble Space Telescope from impact time T + 15 min to T + 18.5 days at spatial resolutions of around 2.1 km per pixel. Our observations reveal the complex evolution of the ejecta, which are first dominated by the gravitational interaction between the Didymos binary system and the ejected dust and subsequently by solar radiation pressure. The lowest-speed ejecta dispersed through a sustained tail that had a consistent morphology with previously observed asteroid tails thought to be produced by an impact4,5. The evolution of the ejecta after the controlled impact experiment of DART thus provides a framework for understanding the fundamental mechanisms that act on asteroids disrupted by a natural impact1,6.

3.
Nature ; 553(7687): 186-188, 2018 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-29323296

RESUMEN

Cometary outgassing can produce torques that change the spin state of the cometary nucleus, which in turn influences the evolution and lifetime of the comet. If these torques increase the rate of rotation to the extent that centripetal forces exceed the material strength of the nucleus, the comet can fragment. Torques that slow down the rotation can cause the spin state to become unstable, but if the torques persist the nucleus can eventually reorient itself and the rotation rate can increase again. Simulations predict that most comets go through a short phase of rapid changes in spin state, after which changes occur gradually over longer times. Here we report observations of comet 41P/Tuttle-Giacobini-Kresák during its close approach to Earth (0.142 astronomical units, approximately 21 million kilometres, on 1 April 2017) that reveal a rapid decrease in rotation rate. Between March and May 2017, the apparent rotation period of the nucleus increased from 20 hours to more than 46 hours-a rate of change of more than an order of magnitude larger than has hitherto been measured. This phenomenon must have been caused by the gas emission from the comet aligning in such a way that it produced an anomalously strong torque that slowed the spin rate of the nucleus. The behaviour of comet 41P/Tuttle-Giacobini-Kresák suggests that it is in a distinct evolutionary state and that its rotation may be approaching the point of instability.

4.
Age Ageing ; 53(1)2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38275097

RESUMEN

OBJECTIVE: To examine the feasibility of using allied health assistants to deliver patient falls prevention education within 48 h after hospital admission. DESIGN AND SETTING: Feasibility study with hospital patients randomly allocated to usual care or usual care plus additional patient falls prevention education delivered by supervised allied health assistants using an evidence-based scripted conversation and educational pamphlet. PARTICIPANTS: (i) allied health assistants and (ii) patients admitted to participating hospital wards over a 20-week period. OUTCOMES: (i) feasibility of allied health assistant delivery of patient education; (ii) hospital falls per 1,000 bed days; (iii) injurious falls; (iv) number of falls requiring transfer to an acute medical facility. RESULTS: 541 patients participated (median age 81 years); 270 control group and 271 experimental group. Allied health assistants (n = 12) delivered scripted education sessions to 254 patients in the experimental group, 97% within 24 h after admission. There were 32 falls in the control group and 22 in the experimental group. The falls rate was 8.07 falls per 1,000 bed days in the control group and 5.69 falls per 1,000 bed days for the experimental group (incidence rate ratio = 0.66 (95% CI 0.32, 1.36; P = 0.26)). There were 2.02 injurious falls per 1,000 bed days for the control group and 1.03 for the experimental group. Nine falls (7 control, 2 experimental) required transfer to an acute facility. No adverse events were attributable to the experimental group intervention. CONCLUSIONS: It is feasible and of benefit to supplement usual care with patient education delivered by allied health assistants.


Asunto(s)
Hospitalización , Hospitales , Anciano de 80 o más Años , Humanos , Estudios de Factibilidad , Recursos Humanos
5.
Immunol Rev ; 296(1): 191-204, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32666572

RESUMEN

Natural influenza virus infections and seasonal vaccinations often do not confer broadly neutralizing immunity across diverse influenza strains. In addition, the virus is capable of rapid antigenic drift in order to evade pre-existing immunity. The surface glycoproteins, hemagglutinin, and neuraminidase can easily mutate their immunodominant epitopes without impacting fitness. Skewing human antibody repertoires to target more conserved epitopes is thus an expanding area of research: Many groups are attempting to produce universal influenza vaccines that can protect across a wide variety of strains. Achieving this goal will require a detailed understanding of how infection history impacts humoral responses. It will also require the ability to manipulate or enhance B cell selection in order to expand clones that can recognize subdominant but protective epitopes. In this review, we will discuss what immune imprinting means to immunologists and describe efforts to overcome or silence imprinting in order to improve vaccination efficiency.


Asunto(s)
Interacciones Huésped-Patógeno/inmunología , Epítopos Inmunodominantes/inmunología , Gripe Humana/inmunología , Orthomyxoviridae/inmunología , Animales , Antígenos Virales/inmunología , Selección Clonal Mediada por Antígenos , Humanos , Inmunidad Celular , Inmunidad Humoral , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Vacunación
6.
Artículo en Inglés | MEDLINE | ID: mdl-37953414

RESUMEN

OBJECTIVES: This study aimed to synthesise the psychosocial stressors of siblings of people with experiences of psychosis (SOPEP). Understanding the specific needs of siblings across diverse cultures would help mental health services to provide culturally specific psychosocial family and sibling-centred support. This may result in improved relationships between families, better psychosocial well-being for siblings and better outcomes for patients. METHODS: Following PRISMA guidelines, a systematic review was conducted to explore the psychosocial stressors of SOPEP. Six databases were utilised to identify literature using qualitative methodology. RESULTS: Twenty-two studies were included that investigated the Psychosocial Stressors of SOPEP. SOPEP's experiences were influenced by various stages: individual factors, social factors, physical and macro-level environments. Six key components contributed to SOPEP's psychosocial stressors and facilitated or hindered their intentions, behaviours and experiences of caregiving. These were the SOPEP's beliefs about psychosis, caregiving beliefs, family and cultural values, personality traits, pragmatic challenges and access to resources. CONCLUSIONS: Globally, SOPEP and families may benefit from their involvement in family interventions and individual support that facilitates caregiving and acknowledges their responsibilities, resources, psychosocial needs and emotional experiences.

7.
Lancet ; 396(10243): 39-49, 2020 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-32622394

RESUMEN

BACKGROUND: Primary spontaneous pneumothorax occurs in otherwise healthy young patients. Optimal management is not defined and often results in prolonged hospitalisation. Data on efficacy of ambulatory options are poor. We aimed to describe the duration of hospitalisation and safety of ambulatory management compared with standard care. METHODS: In this open-label, randomised controlled trial, adults (aged 16-55 years) with symptomatic primary spontaneous pneumothorax were recruited from 24 UK hospitals during a period of 3 years. Patients were randomly assigned (1:1) to treatment with either an ambulatory device or standard guideline-based management (aspiration, standard chest tube insertion, or both). The primary outcome was total length of hospital stay including re-admission up to 30 days after randomisation. Patients with available data were included in the primary analysis and all assigned patients were included in the safety analysis. The trial was prospectively registered with the International Standard Randomised Clinical Trials Number, ISRCTN79151659. FINDINGS: Of 776 patients screened between July, 2015, and March, 2019, 236 (30%) were randomly assigned to ambulatory care (n=117) and standard care (n=119). At day 30, the median hospitalisation was significantly shorter in the 114 patients with available data who received ambulatory treatment (0 days [IQR 0-3]) than in the 113 with available data who received standard care (4 days [IQR 0-8]; p<0·0001; median difference 2 days [95% CI 1-3]). 110 (47%) of 236 patients had adverse events, including 64 (55%) of 117 patients in the ambulatory care arm and 46 (39%) of 119 in the standard care arm. All 14 serious adverse events occurred in patients who received ambulatory care, eight (57%) of which were related to the intervention, including an enlarging pneumothorax, asymptomatic pulmonary oedema, and the device malfunctioning, leaking, or dislodging. INTERPRETATION: Ambulatory management of primary spontaneous pneumothorax significantly reduced the duration of hospitalisation including re-admissions in the first 30 days, but at the expense of increased adverse events. This data suggests that primary spontaneous pneumothorax can be managed for outpatients, using ambulatory devices in those who require intervention. FUNDING: UK National Institute for Health Research.


Asunto(s)
Atención Ambulatoria/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Neumotórax/terapia , Nivel de Atención , Adulto , Femenino , Hospitalización , Humanos , Masculino , Reino Unido
8.
Thorax ; 76(7): 696-703, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33692174

RESUMEN

INTRODUCTION: Risk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking. METHODS: Multivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290). RESULTS: 983 patients (median age 70, IQR 53-83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0-1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%). CONCLUSION: The SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.


Asunto(s)
COVID-19/mortalidad , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Monitoreo Ambulatorio/estadística & datos numéricos , Neumonía Viral/mortalidad , Anciano , Anciano de 80 o más Años , Toma de Decisiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad
9.
Eur Respir J ; 57(6)2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33334938

RESUMEN

Secondary spontaneous pneumothorax (SSP) is traditionally managed with an intercostal chest tube attached to an underwater seal. We investigated whether use of a one-way flutter valve shortened patients' length of stay (LoS).This open-label randomised controlled trial enrolled patients presenting with SSP and randomised to either a chest tube and underwater seal (standard care: SC) or ambulatory care (AC) with a flutter valve. The type of flutter valve used depended on whether at randomisation the patient already had a chest tube in place: in those without a chest tube a pleural vent (PV) was used; in those with a chest tube in situ, an Atrium Pneumostat (AP) valve was attached. The primary end-point was LoS.Between March 2017 and March 2020, 41 patients underwent randomisation: 20 to SC and 21 to AC (13=PV, 8=AP). There was no difference in LoS in the first 30 days following treatment intervention: AC (median=6 days, IQR 14.5) and SC (median=6 days, IQR 13.3). In patients treated with PV there was a high rate of early treatment failure (6/13; 46%), compared to patients receiving SC (3/20; 15%) (p=0.11) Patients treated with AP had no (0/8 0%) early treatment failures and a median LoS of 1.5 days (IQR 23.8).There was no difference in LoS between ambulatory and standard care. Pleural Vents had high rates of treatment failure and should not be used in SSP. Atrium Pneumostats are a safer alternative, with a trend towards lower LoS.


Asunto(s)
Neumotórax , Atención Ambulatoria , Tubos Torácicos , Drenaje , Humanos , Tiempo de Internación , Insuficiencia del Tratamiento , Resultado del Tratamiento
10.
Genet Sel Evol ; 53(1): 8, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33461502

RESUMEN

BACKGROUND: Variants that regulate transcription, such as expression quantitative trait loci (eQTL), have shown enrichment in genome-wide association studies (GWAS) for mammalian complex traits. However, no study has reported eQTL in sheep, although it is an important agricultural species for which many GWAS of complex meat traits have been conducted. Using RNA sequence data produced from liver and muscle from 149 sheep and imputed whole-genome single nucleotide polymorphisms (SNPs), our aim was to dissect the genetic architecture of the transcriptome by associating sheep genotypes with three major molecular phenotypes including gene expression (geQTL), exon expression (eeQTL) and RNA splicing (sQTL). We also examined these three types of eQTL for their enrichment in GWAS of multi-meat traits and fatty acid profiles. RESULTS: Whereas a relatively small number of molecular phenotypes were significantly heritable (h2 > 0, P < 0.05), their mean heritability ranged from 0.67 to 0.73 for liver and from 0.71 to 0.77 for muscle. Association analysis between molecular phenotypes and SNPs within ± 1 Mb identified many significant cis-eQTL (false discovery rate, FDR < 0.01). The median distance between the eQTL and transcription start sites (TSS) ranged from 68 to 153 kb across the three eQTL types. The number of common variants between geQTL, eeQTL and sQTL within each tissue, and the number of common variants between liver and muscle within each eQTL type were all significantly (P < 0.05) larger than expected by chance. The identified eQTL were significantly (P < 0.05) enriched in GWAS hits associated with 56 carcass traits and fatty acid profiles. For example, several geQTL in muscle mapped to the FAM184B gene, hundreds of sQTL in liver and muscle mapped to the CAST gene, and hundreds of sQTL in liver mapped to the C6 gene. These three genes are associated with body composition or fatty acid profiles. CONCLUSIONS: We detected a large number of significant eQTL and found that the overlap of variants between eQTL types and tissues was prevalent. Many eQTL were also QTL for meat traits. Our study fills a gap in the knowledge on the regulatory variants and their role in complex traits for the sheep model.


Asunto(s)
Hígado/metabolismo , Músculo Esquelético/metabolismo , Polimorfismo Genético , Sitios de Carácter Cuantitativo , Carne Roja/normas , Ovinos/genética , Animales , Ácidos Grasos/metabolismo , Femenino , Masculino , Carácter Cuantitativo Heredable , Transcriptoma
11.
PLoS Pathog ; 14(1): e1006874, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29370315

RESUMEN

Lipid droplet (LD) formation occurs during infection of macrophages with numerous intracellular pathogens, including Mycobacterium tuberculosis. It is believed that M. tuberculosis and other bacteria specifically provoke LD formation as a pathogenic strategy in order to create a depot of host lipids for use as a carbon source to fuel intracellular growth. Here we show that LD formation is not a bacterially driven process during M. tuberculosis infection, but rather occurs as a result of immune activation of macrophages as part of a host defense mechanism. We show that an IFN-γ driven, HIF-1α dependent signaling pathway, previously implicated in host defense, redistributes macrophage lipids into LDs. Furthermore, we show that M. tuberculosis is able to acquire host lipids in the absence of LDs, but not in the presence of IFN-γ induced LDs. This result uncouples macrophage LD formation from bacterial acquisition of host lipids. In addition, we show that IFN-γ driven LD formation supports the production of host protective eicosanoids including PGE2 and LXB4. Finally, we demonstrate that HIF-1α and its target gene Hig2 are required for the majority of LD formation in the lungs of mice infected with M. tuberculosis, thus demonstrating that immune activation provides the primary stimulus for LD formation in vivo. Taken together our data demonstrate that macrophage LD formation is a host-driven component of the adaptive immune response to M. tuberculosis, and suggest that macrophage LDs are not an important source of nutrients for M. tuberculosis.


Asunto(s)
Inmunidad Innata/fisiología , Gotas Lipídicas/metabolismo , Activación de Macrófagos , Macrófagos/metabolismo , Macrófagos/microbiología , Mycobacterium tuberculosis , Animales , Células Cultivadas , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Interferón gamma/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mycobacterium tuberculosis/patogenicidad , Transducción de Señal , Tuberculosis/inmunología , Tuberculosis/microbiología , Tuberculosis/patología
12.
Compr Psychiatry ; 97: 152147, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31838296

RESUMEN

BACKGROUND: Patients with Major Depressive Disorder experience significantly reduced subjective Quality of Life (QOL), including impaired social and emotional functioning and greater fatigue and physical pain. Mounting evidence suggests that cognitive dysfunction (e.g., deficits in memory, executive function) contributes independently to the onset of reduced QOL, however the domain-specific nature of this relationship has not been investigated. The present study examined the relationship between specific cognitive domains (e.g., attention, spatial cognition) and specific deficits in mental and physical QOL in subjects with lifetime MDD, as well as acutely depressed, remitted and healthy participants. METHODS: Data were obtained (N = 387) from the Cognitive Function and Mood Study (COFAMS), a cross-sectional study of emotional, functional and cognitive status in individuals with mood disorders. Participants' (acutely depressed n = 93, remitted n = 170, and healthy control n = 124) QOL was assessed with the 36-Item Short Form Health Survey (SF-36) and cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Colorado Assessment Tests (CATs) and the Psychology Experiment Building Language (PEBL). RESULTS: Analyses revealed that poor immediate and delayed memory were associated with reduced mental QOL in individuals with lifetime MDD, acutely depressed, and healthy controls. In contrast, cognitive functioning was not associated with mental QOL in remitted patients. No cognitive domains were significantly related to physical QOL in any participant group. CONCLUSIONS: The result suggests that deficits in immediate and delayed memory may contribute to reduced mental QOL in acute MDD, whereas cognition does not appear to play a role in physical QOL. Memory should be considered important cognitive treatment targets for MDD patients suffering specifically from reduced mental QOL.


Asunto(s)
Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Disfunción Cognitiva/complicaciones , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Memoria/fisiología , Calidad de Vida/psicología , Actividades Cotidianas/psicología , Adulto , Afecto , Atención/fisiología , Estudios de Casos y Controles , Cognición , Disfunción Cognitiva/psicología , Estudios Transversales , Trastorno Depresivo Mayor/complicaciones , Emociones , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/complicaciones , Pruebas Neuropsicológicas , Dolor/complicaciones , Adulto Joven
13.
Depress Anxiety ; 36(1): 54-62, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30211966

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is associated with social cognitive deficits (e.g., poor affect recognition and impaired theory of mind). However, the contribution of social cognitive issues to psychosocial dysfunction in MDD (e.g., occupational functioning and interpersonal relationships) has not been investigated. The current study evaluated the relationship between specific social cognitive domains (e.g., prosody interpretation) and psychosocial dysfunction in subjects with lifetime MDD, as well as currently depressed, remitted, and healthy controls (HCs) subjects. METHOD: Data were obtained from 213 participants in the Cognitive Function and mood study (CoFaMS), a cross-sectional study of mood, social cognition, cold cognition, and psychosocial functioning in mood disorders. Participants' (current MDD n = 42, remitted MDD n = 69, and HCs n = 102) social cognitive abilities were assessed using the Social Perception subtest of the Wechsler Adult Intelligence Scale, and psychosocial dysfunction was clinically evaluated with the Functioning Assessment Short Test (FAST). RESULTS: The results indicated that prosody interpretation, but not facial affect or meaning interpretation, was associated with psychosocial dysfunction in subjects with lifetime MDD, as well as remitted MDD subjects relative to HCs. In contrast, social cognition was not associated with functioning in participants with current MDD or in HCs. CONCLUSIONS: These results suggest that the relationship between social cognition and psychosocial functioning differs between the acute and remitted stage of illness in MDD, and that prosody interpretation should be considered a treatment target in patients with residual psychosocial issues.


Asunto(s)
Cognición , Trastorno Depresivo Mayor/psicología , Habilidades Sociales , Adulto , Afecto , Trastornos del Conocimiento/psicología , Estudios Transversales , Depresión , Femenino , Humanos , Relaciones Interpersonales , Masculino , Trastornos del Humor , Pruebas Neuropsicológicas , Conducta Social , Percepción Social
15.
J Clin Psychol ; 71(12): 1201-17, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26389845

RESUMEN

OBJECTIVE: To increase understanding of the internal processes of recovery in psychosis, with particular consideration given to self-compassion and self-criticism. METHOD: Qualitative data were collected by semistructured interviews, from 10 participants with psychosis, and analyzed using interpretative phenomenological analysis. RESULTS: Five superordinate themes emerged: (a) "my mind can't take the load": the "curse" of psychosis; (b) the "trap" of self-criticism; (c) "coming to terms" with psychosis in my life to "move on"; (d) "on my own two feet"; and (e) "an opportunity" for growth. The themes included a reciprocal relationship between psychosis and self-criticism, processes of acceptance, empowerment, and posttraumatic growth. CONCLUSIONS: The internal process of self-to-self relating contributed to 2 maintenance cycles: self-criticism maintained distressing experiences of psychosis and compassionate self-acceptance resulted in empowered action and promoted recovery and growth. The dual process of acceptance and change in relationship to self was central to recovery.


Asunto(s)
Empatía/fisiología , Trastornos Psicóticos/psicología , Autoimagen , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Recuperación de la Función
16.
Cell Physiol Biochem ; 33(6): 1758-77, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24923432

RESUMEN

BACKGROUND/AIMS: Allergen absorption by epithelia may play an important role in downstream immune responses. Transport mechanisms that can bypass Peyer's patches include transcellular and paracellular transport. The capacity of an allergen to cross via these means can modulate downstream processing of the allergen by the immune system. The aim of this study was to investigate allergen-epithelial interactions of peanut allergens with the human intestinal epithelium. METHODS: We achieved this using the human Caco-2 cell culture model, exposed to crude peanut extract. Western and immunofluorescence analysis were used to identify the cellular and molecular changes of peanut extract on the intestinal epithelium. RESULTS: Following exposure of Caco-2 cells to peanut extract, binding of the peanut allergens Ara h 1 and Ara h 2 to the apical cellular membrane and transcytosis across the monolayers were observed. Additionally, the co-localisation of the transmembrane tight junction proteins occludin, JAM-A and claudin-1, with the intracellular adhesion protein ZO-1 was modified. CONCLUSION: Disruption of Caco-2 barrier integrity through tight junction disruption may enable movement of peanut proteins across the intestinal epithelium. This accounts for peanut's increased allergenicity, compared to other food allergens, and provides an explanation for the potency of peanut allergens in immune response elicitation.


Asunto(s)
Arachis/química , Mucosa Intestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Uniones Estrechas/efectos de los fármacos , Albuminas 2S de Plantas/metabolismo , Alérgenos/metabolismo , Antígenos de Plantas/metabolismo , Transporte Biológico , Western Blotting , Células CACO-2 , Moléculas de Adhesión Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Claudina-1/metabolismo , Glicoproteínas/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Proteínas de la Membrana , Microscopía Confocal , Modelos Biológicos , Ocludina/metabolismo , Permeabilidad/efectos de los fármacos , Extractos Vegetales/metabolismo , Proteínas de Plantas/metabolismo , Unión Proteica , Receptores de Superficie Celular/metabolismo , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo
17.
J Dairy Sci ; 97(12): 7325-33, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25282415

RESUMEN

Ribonuclease 5, also known as angiogenin, is a stable and abundant ribonuclease in milk whey protein, which is able to regulate several cellular functions, including capillary formation, neuron survival, and epithelial cell growth. Ribonuclease 5 is important for protein synthesis directly stimulating rRNA synthesis in the nucleolus. Here, we show that biologically active RNase5 can be purified from bovine milk. Furthermore, we show that milk-derived RNase5 directly stimulates muscle cell differentiation in vitro, inducing C2C12 cell differentiation and myogenesis. When supplemented into the diet of healthy adult mice, milk-derived RNase5 preparations promoted muscle weight gain and grip strength. Collectively, these data indicate that milk-derived RNase5 preparations exhibit a novel role in skeletal muscle cell function.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Leche/enzimología , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/crecimiento & desarrollo , Ribonucleasa Pancreática/farmacología , Alimentación Animal , Animales , Bovinos , Línea Celular , Suplementos Dietéticos , Ratones , Leche/química , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/efectos de los fármacos
18.
Clin Child Psychol Psychiatry ; 29(2): 661-673, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37773596

RESUMEN

BACKGROUND: Existing literature implies there may be gaps in post-treatment support for young people with cancer. This service evaluation explored the needs and experiences of young people when ending cancer treatment in a UK children's hospital to inform service provisions. METHODS: Semi-structured interviews were conducted with nine young people, aged 13-18 years, who had finished active cancer treatment and were receiving follow-up care. The data was analysed using thematic analysis. RESULTS: Four main themes were developed: being in the dark (i.e. limited awareness of what happens when treatment ends); separation from the hospital (i.e. the loss of valued support from staff); consequences of cancer (i.e. managing ongoing psychological and physical effects); and getting back to normal life (i.e. shifting from hospital to everyday life). CONCLUSIONS: Recommendations for improving clinical practice were made. Greater preparedness for ending treatment could be achieved by clearly setting out ongoing care arrangements, providing resource packs, having opportunities to mark the end of treatment, and offering peer support. To identify specific post-treatment needs, there should be an end of treatment multidisciplinary review and space for young people to share how they are feeling in follow-up medical appointments.


Asunto(s)
Neoplasias , Aceptación de la Atención de Salud , Niño , Humanos , Adolescente , Investigación Cualitativa , Neoplasias/terapia , Neoplasias/psicología
19.
Early Interv Psychiatry ; 18(5): 293-311, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38356356

RESUMEN

AIM: Access to timely treatment is key to early intervention in psychosis. Despite this, barriers to treatment exist. In this review, we aimed to understand the structural barriers that patients and caregivers face in help-seeking for first-episode psychosis, and the recommendations provided to address these. METHODS: We conducted a systematic review (PROSPERO: CRD42021274609) of qualitative studies reporting structural barriers to help-seeking from the patient or caregiver perspective. Searches were performed in September 2023, restricted to studies published from 2001. Study quality was appraised using Critical Appraisal Skills Programme. Data were analysed using thematic synthesis. RESULTS: Nineteen papers from 11 countries were included. Across all papers, participants reported experiencing structural barriers to receiving healthcare. For many patients and caregivers, the process of accessing healthcare is complex. Access requires knowledge and resources from parents, caregivers and healthcare providers, yet too often there is a misalignment between patients' needs and service resources. Expertise amongst healthcare providers vary and some patients and caregivers experience negative encounters in healthcare. Patients highlighted earlier caregiver involvement and greater peer support as potential routes for improvement. CONCLUSION: Patients and caregivers face multiple structural barriers, with legislative practices that discourage family involvement, and healthcare and transport costs found to be particularly problematic. Understanding these barriers can facilitate the co-design of both new and existing services to provide easier access for patients and caregivers. Further research is needed focusing not only on the perspectives of patients and caregivers who have accessed professional help but also crucially on those who have not.


Asunto(s)
Accesibilidad a los Servicios de Salud , Aceptación de la Atención de Salud , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/terapia , Aceptación de la Atención de Salud/psicología , Cuidadores/psicología , Conducta de Búsqueda de Ayuda , Servicios de Salud Mental
20.
Int J Epidemiol ; 53(3)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38840559

RESUMEN

BACKGROUND: In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. METHODS: Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420 319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. RESULTS: Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. CONCLUSIONS: Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.


Asunto(s)
Teorema de Bayes , Donantes de Sangre , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/sangre , Donantes de Sangre/estadística & datos numéricos , Masculino , Femenino , Adulto , SARS-CoV-2/inmunología , Persona de Mediana Edad , Canadá/epidemiología , Estudios Seroepidemiológicos , Anticuerpos Antivirales/sangre , Adulto Joven , Adolescente , Disparidades en el Estado de Salud , Factores Socioeconómicos , Características de la Residencia , Anciano
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