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1.
J Gambl Stud ; 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38311695

RESUMEN

Gambling and its impacts are an important public health issue. The relationship between gambling, problem gambling and gambling harm is complex and dynamic. Replicate prevalence studies are useful for surveillance and monitoring gambling impacts within jurisdictions. The purpose of this study was to compare changes in gambling and problem gambling in the Victorian adult population between 2008 and 2018 by investigating individual gambling activities and exploring their relationship with the Victorian gambling ecosystem. Gambling participation has decreased; problem gambling prevalence has not. Investigation beyond these summary measures reveals important details: (a) Electronic Gaming Machines (EGMs), casino table games, race and sports betting ('high-risk activities'), informal private betting, and Keno, and their associations with problem gambling endure. Further, the strength of this association is unaffected by changes in product technology, delivery, or the Victorian environment in which they reside, (b) participation in high-risk activities, excluding EGMs, increased while for other activities they decreased, (c) EGMs continue to pose the greatest risk for Victorians, (d) males and young adults continue having a higher problem gambling prevalence rate and preferring both online gambling and high-risk activities (excluding racing favoured by an ageing, older cohort, and Keno, by all ages), and (e) gambling access and exposure proliferated enabling single site multiple gambling opportunities on high-risk activities. Young adults represented a new vulnerable group as they reach the legal gambling age. The most effective interventions (based on major falls in real expenditure (losses) on EGMs, the highest risk activity) were the smoking bans, removal of ATMs from venues and decreases in bet size. There is great potential for prevention, intervention, and minimising harm in the gambling environment.

2.
Br J Dermatol ; 189(6): 674-684, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37722926

RESUMEN

BACKGROUND: Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings. OBJECTIVES: To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial. METHODS: We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2-16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status. RESULTS: In total, 103 participants were randomized (May 2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE. CONCLUSIONS: Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation.


Asunto(s)
Ciclosporina , Dermatitis Atópica , Niño , Humanos , Adolescente , Ciclosporina/efectos adversos , Metotrexato/efectos adversos , Dermatitis Atópica/tratamiento farmacológico , Proteínas Filagrina , Oportunidad Relativa , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Método Doble Ciego
3.
PLoS Genet ; 16(7): e1008812, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32658893

RESUMEN

In Arabidopsis, CONSTANS (CO) integrates light and circadian clock signals to promote flowering under long days (LD). In the grasses, a duplication generated two paralogs designated as CONSTANS1 (CO1) and CONSTANS2 (CO2). Here we show that in tetraploid wheat plants grown under LD, combined loss-of-function mutations in the A and B-genome homeologs of CO1 and CO2 (co1 co2) result in a small (3 d) but significant (P<0.0001) acceleration of heading time both in PHOTOPERIOD1 (PPD1) sensitive (Ppd-A1b, functional ancestral allele) and insensitive (Ppd-A1a, functional dominant allele) backgrounds. Under short days (SD), co1 co2 mutants headed 13 d earlier than the wild type (P<0.0001) in the presence of Ppd-A1a. However, in the presence of Ppd-A1b, spikes from both genotypes failed to emerge by 180 d. These results indicate that CO1 and CO2 operate mainly as weak heading time repressors in both LD and SD. By contrast, in ppd1 mutants with loss-of-function mutations in both PPD1 homeologs, the wild type Co1 allele accelerated heading time >60 d relative to the co1 mutant allele under LD. We detected significant genetic interactions among CO1, CO2 and PPD1 genes on heading time, which were reflected in complex interactions at the transcriptional and protein levels. Loss-of-function mutations in PPD1 delayed heading more than combined co1 co2 mutations and, more importantly, PPD1 was able to perceive and respond to differences in photoperiod in the absence of functional CO1 and CO2 genes. Similarly, CO1 was able to accelerate heading time in response to LD in the absence of a functional PPD1. Taken together, these results indicate that PPD1 and CO1 are able to respond to photoperiod in the absence of each other, and that interactions between these two photoperiod pathways at the transcriptional and protein levels are important to fine-tune the flowering response in wheat.


Asunto(s)
Epistasis Genética/genética , Fotoperiodo , Proteínas de Plantas/genética , Triticum/genética , Alelos , Arabidopsis , Relojes Circadianos/genética , Ritmo Circadiano/genética , Flores/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas/genética , Genotipo , Factores de Transcripción/genética , Triticum/crecimiento & desarrollo
4.
J Exp Bot ; 70(1): 193-204, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30295847

RESUMEN

FLOWERING LOCUS T2 (FT2) is the closest paralog of the FT1 flowering gene in the temperate grasses. Here we show that overexpression of FT2 in Brachypodium distachyon and barley results in precocious flowering and reduced spikelet number, while down-regulation by RNA interference results in delayed flowering and a reduced percentage of filled florets. Similarly, truncation mutations of FT2 homeologs in tetraploid wheat delayed flowering (2-4 d) and reduced fertility. The wheat ft2 mutants also showed a significant increase in the number of spikelets per spike, with a longer spike development period potentially contributing to the delayed heading time. In the wheat leaves, FT2 was expressed later than FT1, suggesting a relatively smaller role for FT2 in the initiation of the reproductive phase. FT2 transcripts were detected in the shoot apical meristem and increased during early spike development. Transversal sections of the developing spike showed the highest FT2 transcript levels in the distal part, where new spikelets are formed. Our results suggest that, in wheat, FT2 plays an important role in spike development and fertility and a limited role in the timing of the transition between the vegetative and reproductive shoot apical meristem.


Asunto(s)
Brachypodium/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Hordeum/genética , Proteínas de Plantas/genética , Triticum/genética , Brachypodium/crecimiento & desarrollo , Fertilidad/genética , Flores/genética , Genes de Plantas/genética , Hordeum/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Reproducción/genética , Triticum/crecimiento & desarrollo
5.
Pediatr Dermatol ; 36(5): 725-727, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31318095

RESUMEN

Fanconi anemia is a rare, autosomal recessive genomic instability disorder characterized by congenital limb anomalies, panmyelopathy and a high risk of malignancy, principally acute myeloid leukemia. Hematologic malignancy presenting with acute febrile neutrophilic dermatosis (Sweet syndrome), both deep and superficial forms, is well described in Fanconi anemia patients but is a rare phenomenon in otherwise healthy children. We present a case of panniculitis (presumptive subcutaneous Sweet syndrome) heralding transformation to acute myeloid leukemia in a 3-year-old boy with a severe Fanconi anemia phenotype.


Asunto(s)
Médula Ósea/patología , Anemia de Fanconi/patología , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/patología , Paniculitis/patología , Síndrome de Sweet/patología , Preescolar , Humanos , Masculino
6.
Plant Physiol ; 174(2): 1139-1150, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28408541

RESUMEN

Plants utilize variation in day length (photoperiod) to anticipate seasonal changes. They respond by modulating their growth and development to maximize seed production, which in cereal crops is directly related to yield. In wheat (Triticum aestivum), the acceleration of flowering under long days (LD) is dependent on the light induction of PHOTOPERIOD1 (PPD1) by phytochromes. Under LD, PPD1 activates FLOWERING LOCUS T1 (FT1), a mobile signaling protein that travels from the leaves to the shoot apical meristem to promote flowering. Here, we show that the interruption of long nights by short pulses of light ("night-break" [NB]) accelerates wheat flowering, suggesting that the duration of the night is critical for wheat photoperiodic response. PPD1 transcription was rapidly upregulated by NBs, and the magnitude of this induction increased with the length of darkness preceding the NB Cycloheximide abolished the NB up-regulation of PPD1, suggesting that this process is dependent on active protein synthesis during darkness. While one NB was sufficient to induce PPD1, more than 15 NBs were required to induce high levels of FT1 expression and a strong acceleration of flowering. Multiple NBs did not affect the expression of core circadian clock genes. The acceleration of flowering by NB disappeared in ppd1-null mutants, demonstrating that this response is mediated by PPD1 The acceleration of flowering was strongest when NBs were applied in the middle of the night, suggesting that in addition to PPD1, other circadian-controlled factors are required for the up-regulation of FT1 expression and the acceleration of flowering.


Asunto(s)
Oscuridad , Flores/fisiología , Fotoperiodo , Proteínas de Plantas/metabolismo , Triticum/fisiología , Alelos , Relojes Circadianos/genética , Flores/genética , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Modelos Biológicos , Fitocromo/metabolismo , Proteínas de Plantas/genética , Biosíntesis de Proteínas , Factores de Tiempo , Transcripción Genética , Triticum/genética
7.
Pediatr Dermatol ; 33(2): e95-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26860318

RESUMEN

We report the case of a young girl who presented with hemiparesis, seizures, and subtle features consistent with a linear form of facial morphea (en coup de sabre). She was treated with pulsed parenteral steroids and oral steroids and started on methotrexate. Magnetic resonance imaging results and neurologic problems improved after 6 months. Switching off inflammation early in the course of disease seemed to reverse some of the central nervous system changes. Assessment of children with unexplained hemiparesis and seizures should include careful examination of the face and scalp, looking for subtle signs of skin change and asymmetry. This is one of the few reported cases of neuroradiologic improvement after immunosuppressive treatment in a child with en coup de sabre.


Asunto(s)
Cara/patología , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Esclerodermia Localizada/diagnóstico por imagen , Esclerodermia Localizada/tratamiento farmacológico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Consanguinidad , Intervención Médica Temprana , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerodermia Localizada/diagnóstico , Tomografía Computarizada por Rayos X
8.
Arch Dis Child Educ Pract Ed ; 100(2): 64-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25406412

RESUMEN

Eczema herpeticum (EH) occurs when there is secondary skin infection with herpes simplex virus in an atopic patient. The patient may not have unusually severe or active eczema. It is thought that the abnormal skin barrier function predisposes to infection, which can spread rapidly. Viraemia and secondary septicaemia can occur, and the condition can be life-threatening. The first episode of herpes infection is usually the worst and requires systemic treatment. Early recognition is vital. The presentation may be difficult to distinguish from secondary bacterial infection, which is common in eczema. A useful clinical clue is the presence of many very similar shaped and sized eroded lesions. Intact blisters may not be seen due to scratching. A rapid deterioration in eczema in a child who is systemically unwell should prompt consideration of EH.


Asunto(s)
Erupción Variceliforme de Kaposi/diagnóstico , Erupción Variceliforme de Kaposi/tratamiento farmacológico , Simplexvirus/aislamiento & purificación , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Preescolar , Humanos , Masculino
10.
Plant J ; 71(1): 71-84, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22372488

RESUMEN

Flowering time is a trait that has been extensively altered during wheat domestication, enabling it to be highly productive in diverse environments and providing a rich source of variation for studying adaptation mechanisms. Hexaploid wheat is ancestrally a long-day plant, but many environments require varieties with photoperiod insensitivity (PI) that can flower in short days. PI results from mutations in the Ppd-1 gene on the A, B or D genomes, with individual mutations conferring different degrees of earliness. The basis of this is poorly understood. Using a common genetic background, the effects of A, B and D genome PI mutations on genes of the circadian clock and photoperiod pathway were studied using genome-specific expression assays. Ppd-1 PI mutations did not affect the clock or immediate clock outputs, but affected TaCO1 and TaFT1, with a reduction in TaCO1 expression as TaFT1 expression increased. Therefore, although Ppd-1 is related to PRR genes of the Arabidopsis circadian clock, Ppd-1 affects flowering by an alternative route, most likely by upregulating TaFT1 with a feedback effect that reduces TaCO1 expression. Individual genes in the circadian clock and photoperiod pathway were predominantly expressed from one genome, and there was no genome specificity in Ppd-1 action. Lines combining PI mutations on two or three genomes had enhanced earliness with higher levels, but not earlier induction, of TaFT1, showing that there is a direct quantitative relationship between Ppd-1 mutations, TaFT1 expression and flowering.


Asunto(s)
Flores/fisiología , Genoma de Planta , Mutación , Fotoperiodo , Triticum/genética , Relojes Circadianos , Cruzamientos Genéticos , Flores/genética , Regulación de la Expresión Génica de las Plantas , Poliploidía , Triticum/fisiología
11.
J Psychoactive Drugs ; 55(2): 151-158, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35315749

RESUMEN

The field of psychedelic research is undergoing a revival, yet research focused on non-clinical psychedelic use remains relatively limited. The current qualitative study sheds light on how people use magic mushrooms, what they perceive the effects of such use to be, and the meanings that users attach to their magic mushroom experiences. To be eligible to participate in the study, participants were required to be young adults who had used magic mushrooms within the past three months and residents of Victoria, Canada. Semi-structured, one-on-one in-person interviews regarding magic mushroom use habits, culture, knowledge and other factors were conducted with each participant and subsequently analyzed thematically. Participants associated magic mushroom use with lasting impacts on their lives including transformation and learning experiences. Additionally, participants described strategies to optimize their magic mushroom experiences, including engaging in research regarding magic mushrooms as well as making use of peer supports. Furthermore, aspects of magic mushroom experiences conceptualized as harmful in previous studies were described by participants as associated with learning experiences and few harms. Participants' perceived positive outcomes and relatively low risk profile warrants further research to inform how magic mushroom users can maximize potential positive outcomes and also minimize harms.


Asunto(s)
Alucinógenos , Psilocybe , Adulto Joven , Humanos , Alucinógenos/efectos adversos , Psilocibina , Investigación Cualitativa
12.
Front Plant Sci ; 14: 1321555, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38312357

RESUMEN

The challenges facing tree orchard production in the coming years will be largely driven by changes in the climate affecting the sustainability of farming practices in specific geographical regions. Identifying key traits that enable tree crops to modify their growth to varying environmental conditions and taking advantage of new crop improvement opportunities and technologies will ensure the tree crop industry remains viable and profitable into the future. In this review article we 1) outline climate and sustainability challenges relevant to horticultural tree crop industries, 2) describe key tree crop traits targeted for improvement in agroecosystem productivity and resilience to environmental change, and 3) discuss existing and emerging genomic technologies that provide opportunities for industries to future proof the next generation of orchards.

13.
J Adv Pract Oncol ; 13(3): 298-301, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35663156

RESUMEN

At JADPRO Live Virtual 2021, Sara M. Tolaney, MD, MPH, and Lindsay Shaw, ANP-BC, AOCNP®, presented on recent clinical trial data for approved immune checkpoint inhibitors and antibody-drug conjugates, and their implications in the current treatment landscape, for metastatic triple-negative breast cancer. Dr. Tolaney and Ms. Shaw also discussed principles of monitoring and managing adverse events associated with immunotherapies.

14.
Plants (Basel) ; 11(3)2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35161230

RESUMEN

High-quality DNA and RNA forms the basis of genomic and genetic investigations. The extraction of DNA and RNA from woody trees, like avocado (Persea americana Mill.), is challenging due to compounds which interact with nucleic acids and influence separation. Previously reported methods of DNA and RNA extraction from avocado have issues of low yield, quality and applicability across different cultivars and tissue types. In the current study, methods have been optimised for high-quality DNA extraction from 40 avocado cultivars and RNA extraction from multiple tissue types, including roots, stem, leaves, flowers and fruits. The method is based on the modification of the cetyltrimethylammonium bromide buffer, centred around the specific optimisation of chemicals, such as sodium dodecyl sulphate, polyvinylpyrrolidone, sodium sulphite, polyethylene glycol and ß-mercaptoethanol. The DNA extraction method yielded high-molecular weight DNA from the leaf tissue of 40 avocado cultivars belonging to Mexican, Guatemalan and West Indian avocado horticultural groups. The method was further optimised for RNA extraction from different avocado plant parts, enabling extraction using amounts as low as ~10 mg of starting material. The DNA and RNA extracted was successfully used for long- and short-read sequencing and gene expression analysis. The methods developed may also be applicable to other recalcitrant plant species.

15.
Hortic Res ; 9: uhac157, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36204209

RESUMEN

Avocado (Persea americana) is a member of the magnoliids, an early branching lineage of angiosperms that has high value globally with the fruit being highly nutritious. Here, we report a chromosome-level genome assembly for the commercial avocado cultivar Hass, which represents 80% of the world's avocado consumption. The DNA contigs produced from Pacific Biosciences HiFi reads were further assembled using a previously published version of the genome supported by a genetic map. The total assembly was 913 Mb with a contig N50 of 84 Mb. Contigs assigned to the 12 chromosomes represented 874 Mb and covered 98.8% of benchmarked single-copy genes from embryophytes. Annotation of protein coding sequences identified 48 915 avocado genes of which 39 207 could be ascribed functions. The genome contained 62.6% repeat elements. Specific biosynthetic pathways of interest in the genome were investigated. The analysis suggested that the predominant pathway of heptose biosynthesis in avocado may be through sedoheptulose 1,7 bisphosphate rather than via alternative routes. Endoglucanase genes were high in number, consistent with avocado using cellulase for fruit ripening. The avocado genome appeared to have a limited number of translocations between homeologous chromosomes, despite having undergone multiple genome duplication events. Proteome clustering with related species permitted identification of genes unique to avocado and other members of the Lauraceae family, as well as genes unique to species diverged near or prior to the divergence of monocots and eudicots. This genome provides a tool to support future advances in the development of elite avocado varieties with higher yields and fruit quality.

16.
JBI Evid Synth ; 19(8): 1844-1886, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33993147

RESUMEN

OBJECTIVE: The objective of this scoping review was to describe the characteristics of interventions and programs that support the health and development of infants in foster care who have prenatal substance exposure, their foster care providers, and birth families. INTRODUCTION: Infants in foster care may have experienced prenatal substance exposure, neglect, and maltreatment, as well as disruptions in their relationships with primary caregivers. Despite multiple vulnerabilities, they also have great capacity for overcoming early adversities. Enhanced foster care has been identified as a key influence on the positive development of infants in the child welfare system. INCLUSION CRITERIA: This scoping review considered publications that described interventions and programs designed to support foster care providers who care for infants less than 12 months of age with prenatal substance exposure. This review included research studies and gray literature. This scoping review focused on sources that described caregiving interventions and elements of programs that took place within the context of family or home-based foster care. METHODS: A three-step search strategy was used to identify publications in the English language from January 2000 to December 2019. A literature search was conducted using MEDLINE, Academic Search Premier, PsycINFO, and CINAHL databases. Titles and abstracts were initially screened to assess if publications met the inclusion criteria, followed by full-text review. Publications that met the inclusion criteria were assessed by two independent reviewers using a data extraction tool developed for this review. Findings were thematically analyzed on the basis of similarity in focus and descriptively presented with tables and figures to support the findings. RESULTS: Eighty-one publications were included, including 48 research papers and 33 gray literature sources. Thematic analysis of the focus of each publication resulted in identification of four core themes: i) mental health promotion for infants in care; ii) child welfare program elements; iii) identification of infants and families at risk of requiring foster care; and iv) outcomes for infants in care and their families. The interventions and programs identified during this scoping review were primarily focused on supporting social-emotional development. With the significant focus on infant mental health, supporting birth parents to stay attached to their infants was a key focus of the majority of publications. The concept of being able to proactively identify risk factors that were associated with infants requiring foster care emerged in relation to how family preservation could be supported. Strategies identified as contributing to the development of successful interventions and programs included having foster care providers participate as collaborators in designing services, designing services that are adaptable to a range of contexts, involving community partners outside child welfare, and having developmentally appropriate programs. CONCLUSIONS: Infants represent a significant proportion of children in foster care. A developmental perspective is needed for child welfare service planning to address their unique needs. Intervention during the early years holds significant potential for promoting positive developmental pathways and family preservation.


Asunto(s)
Cuidados en el Hogar de Adopción , Servicios de Atención de Salud a Domicilio , Niño , Protección a la Infancia , Atención a la Salud , Familia , Femenino , Humanos , Lactante , Embarazo
17.
Pediatr Rheumatol Online J ; 19(1): 42, 2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33757522

RESUMEN

BACKGROUND: The aim of this study was to: (i) describe the abnormalities seen on brain imaging in a group of children with en coup de sabre (EDCS) with/without Parry-Romberg syndrome (PRS); and (ii) identify clinical predictors of brain imaging abnormalities. METHODS: This was a single centre (Great Ormond Street Hospital, London) retrospective case series of patients with ECDS/PRS seen from 2000 to 2018. We identified patients with cutaneous manifestations consistent with the clinical descriptions of ECDS/PRS. Presenting clinical, laboratory, and radiological brain findings are described. Results are expressed as medians and ranges or frequencies and percentages. Fisher's exact test was used to identify clinical associations with magnetic resonance imaging (MRI) abnormalities. RESULTS: Fourteen patients were studied: 6 males and 8 females; median age 14 years (range 3-20). We observed neuroimaging abnormalities in 2/6 ECDS and 5/8 ECDS/PRS patients. White matter signal abnormality, dystrophic calcification, leptomeningeal enhancement, and sulcal crowding were the typical findings on brain imaging. A total of 50% of patients had no MRI abnormality despite some of these patients having neurological symptoms. The presence of seizures was significantly associated with ipsilateral enhanced white matter signalling on MRI (p < 0.05). CONCLUSIONS: In summary, we observed several distinct radiographic patterns associated with ECDS/PRS. Seizure disorder was strongly associated with the presence of ipsilateral enhanced white matter signalling. Improved neuroimaging techniques that combine morphological with functional imaging may improve the detection rate of brain involvement in children with ECDS/PRS in the future.


Asunto(s)
Hemiatrofia Facial/diagnóstico por imagen , Imagen por Resonancia Magnética , Esclerodermia Localizada/diagnóstico por imagen , Adolescente , Niño , Preescolar , Hemiatrofia Facial/complicaciones , Femenino , Humanos , Masculino , Estudios Retrospectivos , Esclerodermia Localizada/complicaciones , Adulto Joven
18.
AMRC Open Res ; 3: 20, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-38708070

RESUMEN

Background: Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. Methods: An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. Results: An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Conclusions: Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

19.
Postgrad Med J ; 86(1018): 466-71, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20709768

RESUMEN

Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind. Treatments for vitiligo are generally unsatisfactory. The initial approach to a patient who is thought to have vitiligo is to make a definite diagnosis, offer psychological support, and suggest supportive treatments such as the use of camouflage cosmetics and sunscreens, or in some cases after discussion the option of no treatment. Active therapies open to the non-specialist, after an explanation of potential side effects, include the topical use of potent or highly potent steroids or calcineurin inhibitors for a defined period of time (usually 2 months), following which an assessment is made to establish whether or not there has been a response. Patients whose condition is difficult to diagnose, unresponsive to straightforward treatments, or is causing psychological distress, are usually referred to a dermatologist. Specialist dermatology units have at their disposal phototherapy, either narrow band ultraviolet B or in some cases photochemotherapy, which is the most effective treatment presently available and can be considered for symmetrical types of vitiligo. Depigmenting treatments and possibly surgical approaches may be appropriate for vitiligo in selected cases. There is no evidence that presently available systemic treatments are helpful and safe in vitiligo. There is a need for further research into the causes of vitiligo, and into discovering better treatments.


Asunto(s)
Vitíligo/diagnóstico , Vitíligo/terapia , Inhibidores de la Calcineurina , Medicina Basada en la Evidencia/métodos , Glucocorticoides/uso terapéutico , Humanos , Fototerapia/métodos , Guías de Práctica Clínica como Asunto
20.
Funct Integr Genomics ; 9(4): 485-98, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19578911

RESUMEN

DNA binding with One Finger (Dof) protein is a plant-specific transcription factor implicated in the regulation of many important plant-specific processes, including photosynthesis and carbohydrate metabolism. This study has identified 31 Dof genes (TaDof) in bread wheat through extensive analysis of current nucleotide databases. Phylogenetic analysis suggests that the TaDof family can be divided into four clades. Expression analysis of the TaDof family across all major organs using quantitative RT-PCR and searches of the wheat genome array database revealed that the majority of TaDof members were predominately expressed in vegetative organs. A large number of TaDof members were down-regulated by drought and/or were responsive to the light and dark cycle. Further expression analysis revealed that light up-regulated TaDof members were highly correlated in expression with a number of genes that are involved in photosynthesis or sucrose transport. These data suggest that the TaDof family may have an important role in light-mediated gene regulation, including involvement in the photosynthetic process.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Luz , Proteínas de Plantas/genética , Factores de Transcripción/genética , Triticum , Secuencia de Aminoácidos , Perfilación de la Expresión Génica , Genoma de Planta , Datos de Secuencia Molecular , Fotosíntesis/fisiología , Filogenia , Proteínas de Plantas/clasificación , Proteínas de Plantas/metabolismo , Alineación de Secuencia , Factores de Transcripción/clasificación , Factores de Transcripción/metabolismo , Triticum/genética , Triticum/metabolismo
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