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1.
Chem Rev ; 122(19): 15450-15500, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-35894820

RESUMEN

Phase transitions can occur in certain materials such as transition metal oxides (TMOs) and chalcogenides when there is a change in external conditions such as temperature and pressure. Along with phase transitions in these phase change materials (PCMs) come dramatic contrasts in various physical properties, which can be engineered to manipulate electrons, photons, polaritons, and phonons at the nanoscale, offering new opportunities for reconfigurable, active nanodevices. In this review, we particularly discuss phase-transition-enabled active nanotechnologies in nonvolatile electrical memory, tunable metamaterials, and metasurfaces for manipulation of both free-space photons and in-plane polaritons, and multifunctional emissivity control in the infrared (IR) spectrum. The fundamentals of PCMs are first introduced to explain the origins and principles of phase transitions. Thereafter, we discuss multiphysical nanodevices for electronic, photonic, and thermal management, attesting to the broad applications and exciting promises of PCMs. Emerging trends and valuable applications in all-optical neuromorphic devices, thermal data storage, and encryption are outlined in the end.

2.
Health Expect ; 25(5): 2431-2439, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35818850

RESUMEN

INTRODUCTION: Healthcare facilities adopted restrictive visitor policies as a result of the COVID-19 (COVID) pandemic. Though these measures were necessary to promote the safety of patients, families and healthcare providers, it led to isolation and loneliness amongst acute care inpatients that can undermine patient rehabilitation and recovery. The study objectives were to (1) explore how infection prevention and control (IP&C) measures impacted stakeholders' perceptions of care quality and interactions with others and (2) investigate how these experiences and perceptions varied across stakeholder groups and care settings. METHODS: A qualitative descriptive study was conducted. Patients and their families from an inpatient COVID rehabilitation hospital and healthcare providers from an acute or rehabilitation COVID hospital were interviewed between August 2020 and February 2021. RESULTS: A total of 10 patients, 5 family members and 12 healthcare providers were interviewed. Four major themes were identified: (1) IP&C measures challenged the psychosocial health of all stakeholders across care settings; (2): IP&C measures precipitated a need for greater relational care from HCPs; (3) infection prevention tenets perpetuated COVID-related stigma that stakeholders experienced across care settings; and (4) technology was used to facilitate human connection when IP&C limited physical presence. CONCLUSION: IP&C measures challenged psychosocial health and maintenance of vital human connections. Loneliness and isolation were felt by all stakeholders due to physical distancing and COVID-related stigma. Some isolation was mitigated by the relational care provided by HCPs and technological innovations used. The findings of the study underscore the need to balance safety with psychosocial well-being across care settings and beyond the patient-provider dyad. PATIENT AND PUBLIC CONTRIBUTION: This study was informed by the Patient-Oriented Research Agenda and developed through consultations with patients and family caregivers to identify priority areas for rehabilitation research. Priority areas identified that informed the current study were (1) the need to focus on the psychosocial aspects of recovery from illness and injury and (2) the importance of exploring patients' recovery experiences and needs across the continuum of care. The study protocol, ethics submission, analysis and manuscript preparation were all informed by healthcare providers with lived experience of working in COVID care settings.


Asunto(s)
COVID-19 , Cuidadores , Humanos , Cuidadores/psicología , COVID-19/prevención & control , COVID-19/rehabilitación , Familia , Personal de Salud/psicología , Investigación Cualitativa , Control de Infecciones , Seguridad del Paciente , Continuidad de la Atención al Paciente
3.
J Med Philos ; 47(1): 72-94, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35137173

RESUMEN

In debates over the regulation of communication related to dual-use research, the risks that such communication creates must be weighed against against the value of scientific autonomy. The censorship of such communication seems justifiable in certain cases, given the potentially catastrophic applications of some dual-use research. This conclusion however, gives rise to another kind of danger: that regulators will use overly simplistic cost-benefit analysis to rationalize excessive regulation of scientific research. In response to this, we show how institutional design principles and normative frameworks from free speech theory can be used to help extend the argument for regulating dangerous dual-use research beyond overly simplistic cost-benefit reasoning, but without reverting to an implausibly absolutist view of scientific autonomy.


Asunto(s)
Comunicación , Disentimientos y Disputas , Humanos , Autonomía Personal
4.
J Neurol Neurosurg Psychiatry ; 90(9): 1051-1058, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31196913

RESUMEN

OBJECTIVE: Impairment of mental well-being (anxiety, depression, stress) is common among people with multiple sclerosis (PwMS). Treatment options are limited, particularly for anxiety. The aim of this study was to update our previous systematic review (2014) and evaluate via meta-analysis the efficacy of mindfulness-based interventions (MBIs) for improving mental well-being in PwMS. METHODS: Systematic searches for eligible randomised controlled trials (RCTs) were carried out in seven major databases (November 2017, July 2018), using medical subject headings and key words. Studies were screened, data extracted, quality appraised and analysed by two independent reviewers, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Mental well-being was the primary outcome. Random effects model meta-analysis was performed, with effect size reported as standardised mean difference (SMD). RESULTS: Twelve RCTs including 744 PwMS were eligible for inclusion in the systematic review, eight had data extractable for meta-analysis; n=635. Ethnicity, socioeconomic status, comorbidity and disability were inconsistently reported. MBIs varied from manualised to tailored versions, lasting 6-9 weeks, delivered individually and via groups, both in person and online. Overall SMD for mental well-being (eight studies) was 0.40 (0.28-0.53), p<0.01, I2=28%; against active comparators only (three studies) SMD was 0.17 (0.01-0.32), p<0.05, I2 =0%. Only three adverse events were reported. CONCLUSIONS: MBIs are effective at improving mental well-being in PwMS. More research is needed regarding optimal delivery method, cost-effectiveness and comparative-effectiveness. PROSPERO REGISTRATION NUMBER: CRD42018093171.


Asunto(s)
Ajuste Emocional , Atención Plena , Esclerosis Múltiple/psicología , Humanos , Atención Plena/métodos , Esclerosis Múltiple/terapia
5.
J Strength Cond Res ; 33(6): 1601-1608, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28426516

RESUMEN

Thomas, C, Ismail, KT, Simpson, R, Comfort, P, Jones, PA, and Dos'Santos, T. Physical profiles of female academy netball players by position. J Strength Cond Res 33(6): 1602-1609, 2019-The purpose of this study was to evaluate the height, body mass, and physical characteristics of female academy netball players by position (centers, defenders, and shooters). Data were collected on 43 regional academy players during the preseason period and comprising height, body mass, and physical characteristics (single-leg hop [SLH], squat jump [SJ], countermovement jump [CMJ], 5- and 10-m sprint, 505 change of direction speed and cardiorespiratory fitness). Defenders and shooters demonstrated significantly (p ≤ 0.05; d ≥ 1.1) greater body mass compared with centers. Defenders demonstrated significantly (p ≤ 0.05; d = 1.6) greater height compared with centers; however, no significant differences were noted between centers and shooters (p = 0.19; d = 0.7) and defenders and shooters (p = 0.70; d = 0.5). Centers performed better during the SLH left leg (p = 0.01; d = 1.0), SJ (p = 0.03; d = 1.1), CMJ (p = 0.01; d = 1.4), 5-m (p = 0.04; d ≥ -0.9) and 10-m sprint (p = 0.01; d = -1.2), 505 left (p ≤ 0.03; d ≥ 1.0), 505 right (p ≤ 0.03; d = 1.3), and cardiorespiratory fitness (p = 0.01; d ≥ 1.2) compared with other positions. No other significant differences were observed. These findings demonstrate that height, body mass, and physical characteristics differ between positions in female netball players and provide normative data for English academy netball players. Strength and conditioning coaches should consider the specific demands on individual positions when training female netball players.


Asunto(s)
Capacidad Cardiovascular , Movimiento , Deportes/fisiología , Adolescente , Estatura , Peso Corporal , Prueba de Esfuerzo , Femenino , Humanos , Carrera
6.
J Infect Dis ; 218(2): 324-335, 2018 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-29236994

RESUMEN

Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Both antibody and T-cell responses against immunodominant GAS virulence factors, including M protein, cross-react with host tissue proteins, triggering an inflammatory response leading to permanent heart damage. However, in some ARF/RHD-endemic regions, throat carriage of GAS is low. Because Streptococcus dysgalactiae subspecies equisimilis organisms, also known as ß-hemolytic group C streptococci and group G streptococci (GGS), also express M protein, we postulated that streptococci other than GAS may have the potential to initiate or exacerbate ARF/RHD. Using a model initially developed to investigate the uniquely human disease of ARF/RHD, we have discovered that GGS causes interleukin 17A/interferon γ-induced myocarditis and valvulitis, hallmarks of ARF/RHD. Remarkably the histological, immunological, and functional changes in the hearts of rats exposed to GGS are identical to those exposed to GAS. Furthermore, antibody cross-reactivity to cardiac myosin was comparable in both GGS- and GAS-exposed animals, providing additional evidence that GGS can induce and/or exacerbate ARF/RHD.


Asunto(s)
Enfermedades Autoinmunes/etiología , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Cardiopatía Reumática/etiología , Infecciones Estreptocócicas/patología , Streptococcus/inmunología , Animales , Antígenos Bacterianos/inmunología , Enfermedades Autoinmunes/microbiología , Enfermedades Autoinmunes/fisiopatología , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/inmunología , Modelos Animales de Enfermedad , Femenino , Enfermedades de las Válvulas Cardíacas/etiología , Enfermedades de las Válvulas Cardíacas/microbiología , Enfermedades de las Válvulas Cardíacas/fisiopatología , Miocarditis/etiología , Miocarditis/microbiología , Miocarditis/fisiopatología , Ratas Endogámicas Lew , Cardiopatía Reumática/microbiología , Cardiopatía Reumática/fisiopatología , Streptococcus/patogenicidad
7.
BMC Genomics ; 19(1): 257, 2018 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-29661190

RESUMEN

BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.


Asunto(s)
Actinidia/genética , Genoma de Planta , Genes de Plantas , Genotipo , Anotación de Secuencia Molecular , Proteínas de Plantas/genética
8.
Postgrad Med J ; 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38061076
9.
Rev Physiol Biochem Pharmacol ; 168: 59-118, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26345415

RESUMEN

Microvilli are conventionally regarded as an extension of the small intestinal absorptive surface, but they are also, as latterly discovered, a launching pad for brush border digestive enzymes. Recent work has demonstrated that motor elements of the microvillus cytoskeleton operate to displace the apical membrane toward the apex of the microvillus, where it vesiculates and is shed into the periapical space. Catalytically active brush border digestive enzymes remain incorporated within the membranes of these vesicles, which shifts the site of BB digestion from the surface of the enterocyte to the periapical space. This process enables nutrient hydrolysis to occur adjacent to the membrane in a pre-absorptive step. The characterization of BB digestive enzymes is influenced by the way in which these enzymes are anchored to the apical membranes of microvilli, their subsequent shedding in membrane vesicles, and their differing susceptibilities to cleavage from the component membranes. In addition, the presence of active intracellular components of these enzymes complicates their quantitative assay and the elucidation of their dynamics. This review summarizes the ontogeny and regulation of BB digestive enzymes and what is known of their kinetics and their action in the peripheral and axial regions of the small intestinal lumen.


Asunto(s)
Enzimas/metabolismo , Intestino Delgado/enzimología , Microvellosidades/enzimología , Animales , Enzimas/biosíntesis , Cinética
10.
BMC Neurol ; 17(1): 94, 2017 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-28511703

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a stressful condition. Mental health comorbidity is common. Stress can increase the risk of depression, reduce quality of life (QOL), and possibly exacerbate disease activity in MS. Mindfulness-Based Stress Reduction (MBSR) may help, but has been little studied in MS, particularly among more disabled individuals. METHODS: The objective of this study was to test the feasibility and likely effectiveness of a standard MBSR course for people with MS. Participant eligibility included: age > 18, any type of MS, an Expanded Disability Status Scale (EDSS)

Asunto(s)
Depresión/terapia , Atención Plena , Esclerosis Múltiple/psicología , Estrés Psicológico/terapia , Ansiedad/etiología , Ansiedad/terapia , Trastornos de Ansiedad , Depresión/etiología , Personas con Discapacidad , Humanos , Salud Mental , Esclerosis Múltiple/complicaciones , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Proyectos de Investigación , Estrés Psicológico/etiología , Listas de Espera
11.
BMC Neurol ; 17(1): 52, 2017 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-28320349

RESUMEN

BACKGROUND: Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. METHODS: Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. CONCLUSION: This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined.


Asunto(s)
Ansiedad/terapia , Depresión/terapia , Epilepsia/psicología , Atención Plena/métodos , Calidad de Vida/psicología , Ansiedad/etiología , Depresión/etiología , Epilepsia/complicaciones , Humanos
12.
J Therm Biol ; 63: 124-130, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28010810

RESUMEN

Despite technological advances in thermal sensory equipment, few core temperature (TCORE) measurement techniques have met the established validity criteria in exercise science. Additionally, there is debate as to what method serves as the most practically viable, yet upholds the proposed measurement accuracy. This study assessed the accuracy of current and novel TCORE measurement techniques in comparison to rectal temperature (TREC) as a reference standard. Fifteen well-trained subjects (11 male, 4 female) completed 60min of exercise at an intensity equating to the lactate threshold; measured via a discontinuous exercise test. TREC was significantly elevated from resting values (37.2±0.3°C) at the end of moderate intensity exercise (39.6±0.04°C; P=0.001). Intestinal telemetric pill (TPILL) temperature and temporal artery temperature (TTEM) did not differ significantly from TREC at rest or during exercise (P>0.05). However, aural canal temperature (TAUR) and thermal imaging temperature (TIMA) were both significantly lower than TREC (P<0.05). Bland Altman analysis revealed only TPILL was within acceptable limits of agreement (mean bias; 0.04°C), while TTEM, TAUR and TIMA demonstrated mean bias values outside of the acceptable range (>0.27°C). Against TREC, these results support the use of TPILL over all other techniques as a valid measure of TCORE at rest and during exercise induced hyperthermia. Novel findings illustrate that TIMA (when measured at the inner eye canthus) shows poor agreement to TREC during rest and exercise, which is similar to other 'surface' measures.


Asunto(s)
Temperatura Corporal , Ejercicio Físico , Calor , Hipertermia Inducida , Termometría/métodos , Adulto , Oído/fisiología , Femenino , Humanos , Aparato Lagrimal/fisiología , Masculino , Persona de Mediana Edad , Recto/fisiología , Descanso , Telemetría/métodos , Telemetría/normas , Arterias Temporales/fisiología , Termometría/normas
13.
Nat Mater ; 14(10): 991-5, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26213898

RESUMEN

The extreme electro-optical contrast between crystalline and amorphous states in phase-change materials is routinely exploited in optical data storage and future applications include universal memories, flexible displays, reconfigurable optical circuits, and logic devices. Optical contrast is believed to arise owing to a change in crystallinity. Here we show that the connection between optical properties and structure can be broken. Using a combination of single-shot femtosecond electron diffraction and optical spectroscopy, we simultaneously follow the lattice dynamics and dielectric function in the phase-change material Ge2Sb2Te5 during an irreversible state transformation. The dielectric function changes by 30% within 100 fs owing to a rapid depletion of electrons from resonantly bonded states. This occurs without perturbing the crystallinity of the lattice, which heats with a 2-ps time constant. The optical changes are an order of magnitude larger than those achievable with silicon and present new routes to manipulate light on an ultrafast timescale without structural changes.

14.
J Med Ethics ; 42(11): 742-747, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27558776

RESUMEN

The human faculty of moral judgement is not well suited to address problems, like climate change, that are global in scope and remote in time. Advocates of 'moral bioenhancement' have proposed that we should investigate the use of medical technologies to make human beings more trusting and altruistic and hence more willing to cooperate in efforts to mitigate the impacts of climate change. We survey recent accounts of the proximate and ultimate causes of human cooperation in order to assess the prospects for bioenhancement. We identify a number of issues that are likely to be significant obstacles to effective bioenhancement, as well as areas for future research.

15.
NMR Biomed ; 28(7): 792-800, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25943246

RESUMEN

MRS thermometry has been utilized to measure temperature changes in the brain, which may aid in the diagnosis of brain trauma and tumours. However, the temperature calibration of the technique has been shown to be sensitive to non-temperature-based factors, which may provide unique information on the tissue microenvironment if the mechanisms can be further understood. The focus of this study was to investigate the effects of varied protein content on the calibration of MRS thermometry at 3 T, which has not been thoroughly explored in the literature. The effects of ionic concentration and magnetic field strength were also considered. Temperature reference materials were controlled by water circulation and freezing organic fixed-point compounds (diphenyl ether and ethylene carbonate) stable to within 0.2 °C. The temperature was measured throughout the scan time with a fluoro-optic probe, with an uncertainty of 0.16 °C. The probe was calibrated at the National Physical Laboratory (NPL) with traceability to the International Temperature Scale 1990 (ITS-90). MRS thermometry measures were based on single-voxel spectroscopy chemical shift differences between water and N-acetylaspartate (NAA), Δ(H20-NAA), using a Philips Achieva 3 T scanner. Six different phantom solutions with varying protein or ionic concentration, simulating potential tissue differences, were investigated within a temperature range of 21-42 °C. Results were compared with a similar study performed at 1.5 T to observe the effect of field strengths. Temperature calibration curves were plotted to convert Δ(H20-NAA) to apparent temperature. The apparent temperature changed by -0.2 °C/% of bovine serum albumin (BSA) and a trend of 0.5 °C/50 mM ionic concentration was observed. Differences in the calibration coefficients for the 10% BSA solution were seen in this study at 3 T compared with a study at 1.5 T. MRS thermometry may be utilized to measure temperature and the tissue microenvironment, which could provide unique unexplored information for brain abnormalities and other pathologies.


Asunto(s)
Algoritmos , Química Encefálica , Espectroscopía de Resonancia Magnética/métodos , Proteínas/química , Termografía/métodos , Animales , Calibración , Humanos , Concentración de Iones de Hidrógeno , Iones , Campos Magnéticos , Espectroscopía de Resonancia Magnética/normas , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Termografía/normas
16.
Crit Care Nurs Q ; 38(2): 121-36, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25741953

RESUMEN

Treatment of sepsis involves prompt recognition and treatment to optimize outcome. Several medication considerations are pertinent to patients with sepsis, severe sepsis, and septic shock. Medications play a crucial role in providing resuscitation, hemodynamic support, resolution of infection, and reduction of complications of the disease. Over the past 20 years, significant focus has been devoted to the pharmacologic treatment of septic shock, resulting in significant advances and controversies. Ongoing research will continue to focus on this disease process and will continue to shape treatment in the future. The use of medication therapies directed at treatment of sepsis will be reviewed in this article.


Asunto(s)
Antiinfecciosos/uso terapéutico , Fluidoterapia , Sepsis/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Cardiotónicos/uso terapéutico , Fluidoterapia/métodos , Humanos , Sepsis/terapia , Vasoconstrictores/uso terapéutico
17.
Br J Haematol ; 164(4): 586-96, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24236640

RESUMEN

ATOH8 has previously been shown to be an iron-regulated transcription factor, however its role in iron metabolism is not known. ATOH8 expression in HEK293 cells resulted in increased endogenous HAMP mRNA levels as well as HAMP promoter activity. Mutation of the E-box or SMAD response elements within the HAMP promoter significantly reduced the effects of ATOH8, indicating that ATOH8 activates HAMP transcription directly as well as through bone morphogenic protein (BMP) signalling. In support of the former, Chromatin immunoprecipitation assays provided evidence that ATOH8 binds to E-box regions within the HAMP promoter while the latter was supported by the finding that ATOH8 expression in HEK293 cells led to increased phosphorylated SMAD1,5,8 levels. Liver Atoh8 levels were reduced in mice under conditions associated with increased erythropoietic activity such as hypoxia, haemolytic anaemia, hypotransferrinaemia and erythropoietin treatment and increased by inhibitors of erythropoiesis. Hepatic Atoh8 mRNA levels increased in mice treated with holo transferrin, suggesting that Atoh8 responds to changes in plasma iron. ATOH8 is therefore a novel transcriptional regulator of HAMP, which is responsive to changes in plasma iron and erythroid activity and could explain how changes in erythroid activity lead to regulation of HAMP.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Eritropoyesis/genética , Eritropoyesis/fisiología , Hepcidinas/genética , Proteínas Smad/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Femenino , Células HEK293 , Hepcidinas/biosíntesis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Proteínas Smad/genética , Transcripción Genética
18.
J Nutr ; 144(12): 1896-902, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25342699

RESUMEN

BACKGROUND: Iron (Fe) deficiency anemia remains the largest nutritional deficiency disorder worldwide. How the gut acquires iron from nano Fe(III), especially at the apical surface, is incompletely understood. OBJECTIVE: We developed a novel Fe supplement consisting of nanoparticulate tartrate-modified Fe(III) poly oxo-hydroxide [here termed nano Fe(III)], which mimics the Fe oxide core of ferritin and effectively treats iron deficiency anemia in rats. METHODS: We determined transfer to the systemic circulation of nano Fe(III) in iron-deficient and iron-sufficient outbread Swiss mouse strain (CD1) mice with use of (59)Fe-labeled material. Iron deficiency was induced before starting the Fe-supplementation period through reduction of Fe concentrations in the rodent diet. A control group of iron-sufficient mice were fed a diet with adequate Fe concentrations throughout the study. Furthermore, we conducted a hemoglobin repletion study in which iron-deficient CD1 mice were fed for 7 d a diet supplemented with ferrous sulfate (FeSO4) or nano Fe(III). Finally, we further probed the mechanism of cellular acquisition of nano Fe(III) by assessing ferritin formation, as a measure of Fe uptake and utilization, in HuTu 80 duodenal cancer cells with targeted inhibition of divalent metal transporter 1 (DMT1) and duodenal cytochrome b (DCYTB) before exposure to the supplemented iron sources. Differences in gene expression were assessed by quantitative polymerase chain reaction. RESULTS: Absorption (means ± SEMs) of nano Fe(III) was significantly increased in iron-deficient mice (58 ± 19%) compared to iron-sufficient mice (18 ± 17%) (P = 0.0001). Supplementation of the diet with nano Fe(III) or FeSO4 significantly increased hemoglobin concentrations in iron-deficient mice (170 ± 20 g/L, P = 0.01 and 180 ± 20 g/L, P = 0.002, respectively). Hepatic hepcidin mRNA expression reflected the nonheme-iron concentrations of the liver and was also comparable for both nano Fe(III)- and FeSO4-supplemented groups, as were iron concentrations in the spleen and duodenum. Silencing of the solute carrier family 11 (proton-coupled divalent metal ion transporter), member 2 (Slc11a2) gene (DMT1) significantly inhibited ferritin formation from FeSO4 (P = 0.005) but had no effect on uptake and utilization of nano Fe(III). Inhibiting DCYTB with an antibody also had no effect on uptake and utilization of nano Fe(III) but significantly inhibited ferritin formation from ferric nitrilotriacetate chelate (Fe-NTA) (P = 0.04). Similarly, cellular ferritin formation from nano Fe(III) was unaffected by the Fe(II) chelator ferrozine, which significantly inhibited uptake and utilization from FeSO4 (P = 0.009) and Fe-NTA (P = 0.005). CONCLUSIONS: Our data strongly support direct nano Fe(III) uptake by enterocytes as an efficient mechanism of dietary iron acquisition, which may complement the known Fe(II)/DMT1 uptake pathway.


Asunto(s)
Duodeno/citología , Duodeno/efectos de los fármacos , Ferritinas/administración & dosificación , Nanopartículas/química , Anemia Ferropénica/tratamiento farmacológico , Animales , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Línea Celular Tumoral , Suplementos Dietéticos , Duodeno/metabolismo , Enterocitos/metabolismo , Compuestos Férricos/metabolismo , Ferritinas/farmacocinética , Compuestos Ferrosos/administración & dosificación , Compuestos Ferrosos/farmacocinética , Hemoglobinas , Hepcidinas/genética , Hepcidinas/metabolismo , Hierro de la Dieta/administración & dosificación , Hierro de la Dieta/farmacocinética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ácido Nitrilotriacético/análogos & derivados , Ácido Nitrilotriacético/metabolismo , Bazo/efectos de los fármacos , Bazo/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
19.
BMC Neurol ; 14: 128, 2014 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-24925477

RESUMEN

BACKGROUND: Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. METHODS: 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. RESULTS: People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. CONCLUSION: People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation.


Asunto(s)
Estado de Salud , Salud Mental/estadística & datos numéricos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/psicología , Población , Escocia/epidemiología , Factores Socioeconómicos , Adulto Joven
20.
BMC Neurol ; 14: 15, 2014 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-24438384

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a stressful condition; depression, anxiety, pain and fatigue are all common problems. Mindfulness based interventions (MBIs) mitigate stress and prevent relapse in depression and are increasingly being used in healthcare. However, there are currently no systematic reviews of MBIs in people with MS. This review aims to evaluate the effectiveness of MBIs in people with MS. METHODS: Systematic searches were carried out in seven major databases, using both subject headings and key words. Papers were screened, data extracted, quality appraised, and analysed by two reviewers independently, using predefined criteria. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Perceived stress was the primary outcome. Secondary outcomes include mental health, physical health, quality of life, and health service utilisation. Statistical meta-analysis was not possible. Disagreements were adjudicated by a third party reviewer. RESULTS: Three studies (n = 183 participants) were included in the final analysis. The studies were undertaken in Wales (n = 16, randomised controlled trial - (RCT)), Switzerland (n = 150, RCT), and the United States (n = 17, controlled trial). 146 (80%) participants were female; mean age (SD) was 48.6 (9.4) years. Relapsing remitting MS was the main diagnostic category (n = 123, 67%); 43 (26%) had secondary progressive disease; and the remainder were unspecified. MBIs lasted 6-8 weeks; attrition rates were variable (5-43%); all employed pre- post- measures; two had longer follow up; one at 3, and one at 6 months. Socio-economic status of participants was not made explicit; health service utilisation and costs were not reported. No study reported on perceived stress. All studies reported quality of life (QOL), mental health (anxiety and depression), physical (fatigue, standing balance, pain), and psychosocial measures. Statistically significant beneficial effects relating to QOL, mental health, and selected physical health measures were sustained at 3- and 6- month follow up. CONCLUSION: From the limited data available, MBIs may benefit some MS patients in terms of QOL, mental health, and some physical health measures. Further studies are needed to clarify how MBIs might best serve the MS population.


Asunto(s)
Atención Plena/métodos , Esclerosis Múltiple/psicología , Esclerosis Múltiple/terapia , Calidad de Vida/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Ansiedad/terapia , Depresión/epidemiología , Depresión/psicología , Depresión/terapia , Fatiga/epidemiología , Fatiga/psicología , Fatiga/terapia , Humanos , Esclerosis Múltiple/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos
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