RESUMEN
BACKGROUND: MSB11022 is a proposed adalimumab biosimilar. OBJECTIVES: To compare the efficacy, safety and immunogenicity of MSB11022 with reference adalimumab. METHODS: AURIEL-PsO was a double-blind randomized controlled equivalence trial, in which patients with moderate-to-severe chronic plaque-type psoriasis were randomized 1 : 1 to MSB11022 or reference adalimumab. The primary end point was ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16, with a prespecified equivalence interval of ± 18%. Patients with a ≥50% improvement in PASI at week 16 were eligible to enter a double-blind extension period: patients receiving MSB11022 continued treatment, and patients receiving reference adalimumab were rerandomized 1 : 1 either to continue reference adalimumab or to switch to MSB11022. Other efficacy end points and safety, immunogenicity and pharmacokinetic parameters were evaluated at scheduled visits up to weeks 52 (efficacy and immunogenicity), 54 and 66 (safety). RESULTS: In total, 443 patients were randomized. The difference in PASI 75 response rates at week 16 between the treatment arms was -1·9%, and the 95% confidence interval (-7·8% to 4·1%) was within the prespecified equivalence interval. No notable difference in the incidence of treatment-emergent adverse events was observed between treatment arms up to the end of the trial, and no new safety signals were observed. Following treatment switch at week 16, no clinically meaningful differences in safety or immunogenicity were seen between treatment arms through to the end of the observation period. CONCLUSIONS: Therapeutic equivalence between MSB11022 and reference adalimumab was demonstrated. AURIEL-PsO provides evidence to support the similarity of both products with regard to efficacy, safety and immunogenicity. What's already known about this topic? Adalimumab is a fully human antitumour necrosis factor-α monoclonal antibody, indicated for the treatment of multiple inflammatory disorders, including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel diseases and ankylosing spondylitis. MSB11022 is a proposed adalimumab biosimilar that has shown structural and functional similarity to the reference product in an extensive analytical comparability exercise. MSB11022 has demonstrated bioequivalence and comparable safety and immunogenicity profiles in a phase I study in healthy volunteers. What does this study add? This phase III study confirmed equivalent efficacy for MSB11022 and reference adalimumab in patients without any immunomodulation comedication in moderate-to-severe chronic plaque-type psoriasis at week 16. The efficacy, safety and immunogenicity of MSB11022 and reference adalimumab were similar over the respective observation periods (week 52 for efficacy and immunogenicity, week 66 for safety). A switch from reference adalimumab to MSB11022 at week 16 did not impact efficacy, safety or immunogenicity.
Asunto(s)
Adalimumab , Biosimilares Farmacéuticos , Psoriasis , Adalimumab/efectos adversos , Adulto , Biosimilares Farmacéuticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to assess the association of body mass index (BMI) and smoking with risk of revision following total knee replacement (TKR) and total hip replacement (THR). DESIGN: Primary care data, from the Clinical Practice Research Datalink (CPRD), was linked to inpatient hospital records, from Hospital Episode Statistics Admitted Patient Care (HES APC), and covered 1997 to 2014. Parametric survival models, with BMI and smoking status included as explanatory variables, were estimated for 10-year risk of revision and mortality, and were extrapolated to estimate lifetime risk of revision. FINDINGS: TKR and THR cohorts included 10,260 and 10,961 individuals, respectively. For a change in BMI from 25 to 35, the 10-year risk of revision is expected change from 4.6% (3.3-6.4%) to 3.7% (2.6-5.1%) for TKR and 3.7% (2.8-5.1%) to 4.0% (2.8-5.7%) for THR for an otherwise average patient profile. Meanwhile, changing from a non-smoker to a current smoker is expected to change the risk of revision from 4.1% (3.1-5.5%) to 2.8% (1.7-4.7%) for TKR and from 3.8% (2.8-5.3%) to 2.9% (1.9-4.7%) for THR for an otherwise average patient profile. Estimates of lifetime risk were also similar for different values of BMI or smoking status. CONCLUSIONS: Obesity and smoking do not appear to have a meaningful impact on the risk of revision following TKR and THR.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla/efectos adversos , Índice de Masa Corporal , Reoperación/normas , Fumar/efectos adversos , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Factores de RiesgoRESUMEN
Two key moments shaped the extant South Asian gene pool within the last 10 thousand years (ka): the Neolithic period, with the advent of agriculture and the rise of the Harappan/Indus Valley Civilisation; and Late Bronze Age events that witnessed the abrupt fall of the Harappan Civilisation and the arrival of Indo-European speakers. This study focuses on the phylogeographic patterns of mitochondrial haplogroups H2 and H13 in the Indian Subcontinent and incorporates evidence from recently released ancient genomes from Central and South Asia. It found signals of Neolithic arrivals from Iran and later movements in the Bronze Age from Central Asia that derived ultimately from the Steppe. This study shows how a detailed mtDNA phylogeographic approach, combining both modern and ancient variation, can provide evidence of population movements, even in a scenario of strong male bias such as in the case of the Bronze Age Steppe dispersals.
Asunto(s)
ADN Antiguo/análisis , ADN Mitocondrial/análisis , Migración Humana/historia , Arqueología , Asia , Pueblo Asiatico/genética , ADN Mitocondrial/genética , Pool de Genes , Haplotipos , Historia Antigua , Humanos , Irán , FilogeografíaRESUMEN
Objective The main aim of this survey was to determine the frequency of self-reported lower limb or foot and ankle complications experienced by participants with systemic lupus erythematosus (SLE). A secondary aim was to determine the frequency of treatments that have been received or that participants with SLE may like to receive if offered. Method A quantitative, cross-sectional, self-reported survey design was utilized. The developed survey was checked for face and content validity prior to patient partner cognitive debriefing in order to ensure usability, understanding of the process of completion and of the questions posed. The full protocol for survey development has been published previously. Results This is the first comprehensive national UK survey of lower limb and foot health problems reported by participants with SLE. A high prevalence of vascular, dermatological and musculoskeletal complications was reported by survey respondents. Additionally, whilst the relative prevalence of sensory loss was low, a quarter of people reported having had a fall related to changes in foot sensation demonstrating a previously unknown rate and cause of falls. Conclusion Complications related to vascular, dermatological and musculoskeletal health are identified as particularly prevalent in participants with SLE. Further, there is a suggestion that the provision of interventions to maintain lower limb health is highly varied and lacks national standardization, despite there being a strong indication of participant reported need. The findings of this work can be used to inform care guideline development in addition to identifying areas for future research.
Asunto(s)
Accidentes por Caídas , Enfermedades del Pie/fisiopatología , Extremidad Inferior/lesiones , Lupus Eritematoso Sistémico/fisiopatología , Adulto , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Autoinforme , Reino UnidoRESUMEN
Background Systemic lupus erythematosus (SLE) can present with a variety of symptoms. Previous research has shown there is a high prevalence of lower limb and foot problems in patients with SLE associated with the musculoskeletal, vascular and neurological changes. Furthermore, there is a high prevalence of infections affecting the feet and a range of common skin and nail problems. However, it is not known how these foot problems impact upon people's lives. Therefore, we aimed to explore this using a qualitative approach. Method Following ethical approval, 12 participants were recruited who had a diagnosis of SLE, current and/or past experience of foot problems and were over 18 years in age. Following consent, interviews were carried out with an interpretivist phenomenological approach to both data collection and analysis. Results Seven themes provide insight into: foot problems and symptoms; the impact of these foot problems and symptoms on activities; disclosure and diagnosis of foot problems; treatment of foot problems and symptoms; perceived barriers to professional footcare; unanswered questions about feet and footcare; and identification of the need for professional footcare and footcare advice. Conclusion These participants tend to "self-treat" rather than disclose that they may need professional footcare. A lack of focus upon foot health within a medical consultation is attributed to the participant's belief that it is not within the doctor's role, even though it is noted to contribute to reduced daily activity. There is a need for feet to be included as a part of patient monitoring and for foot health management to be made accessible for people with SLE.
Asunto(s)
Enfermedades del Pie/etiología , Lupus Eritematoso Sistémico/complicaciones , Actividades Cotidianas , Adulto , Anciano , Costo de Enfermedad , Femenino , Enfermedades del Pie/diagnóstico , Enfermedades del Pie/terapia , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud , Humanos , Entrevistas como Asunto , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/terapia , Persona de Mediana Edad , Aceptación de la Atención de Salud , Podiatría/métodos , Investigación Cualitativa , Factores de Riesgo , AutocuidadoRESUMEN
To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13â 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.
Asunto(s)
Artritis Juvenil/diagnóstico , Articulaciones , Adolescente , Comités Consultivos , Artritis Juvenil/terapia , Niño , Preescolar , Manejo de la Enfermedad , Humanos , Articulaciones/diagnóstico por imagen , Articulaciones/patología , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Radiografía , Cintigrafía , Reumatología , Tomografía Computarizada por Rayos X , UltrasonografíaAsunto(s)
Artritis Reumatoide , Terapia Biológica , Participación del Paciente , Espondilitis Anquilosante , Adulto , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Terapia Biológica/ética , Terapia Biológica/métodos , Toma de Decisiones/ética , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Uso Fuera de lo Indicado , Participación del Paciente/métodos , Participación del Paciente/psicología , Prioridad del Paciente/estadística & datos numéricos , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/psicología , Encuestas y Cuestionarios , Reino UnidoRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory disease that develops as a result of the interaction between genetic and environmental risk factors. Although increasing evidence shows the importance of genes in determining the risk of RA, it is clear that environmental factors also have a vital role. Studies to date have tended to concentrate on environmental influences around the time of disease onset. However, a number of pieces of evidence, including the fact that autoantibodies, such as rheumatoid factor (RF), can develop several years before the onset of clinical disease, suggest that environmental factors may influence disease susceptibility during early life. Several recent studies lend weight to this possibility, with an increased risk of RA in the offspring of mothers who smoked during pregnancy and in those with higher birth weight. There has also been a suggestion that the risk of RA is reduced in breast-fed infants. We describe the evidence surrounding the effect of early life factors on the risk of developing RA and possible mechanisms by which they may act.
Asunto(s)
Artritis Reumatoide/epidemiología , Artritis Reumatoide/etiología , Lactancia Materna/epidemiología , Infecciones/epidemiología , Artritis Reumatoide/inmunología , Peso al Nacer , Femenino , Humanos , Embarazo , Factor Reumatoide/inmunología , Riesgo , Fumar/efectos adversosRESUMEN
OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.
Asunto(s)
Artritis/diagnóstico , Artritis Reumatoide/diagnóstico , Biomarcadores/sangre , Diagnóstico Diferencial , Medicina Basada en la Evidencia/métodos , Humanos , Cooperación Internacional , Cuidados a Largo Plazo/métodos , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
The paternal origins of Thoroughbred racehorses trace back to a handful of Middle Eastern stallions, imported to the British Isles during the seventeenth century. Yet, few details of the foundation mares were recorded, in many cases not even their names (several different maternal lineages trace back to 'A Royal Mare'). This has fuelled intense speculation over their origins. We examined mitochondrial DNA from 1929 horses to determine the origin of Thoroughbred foundation mares. There is no evidence to support exclusive Arab maternal origins as some historical records have suggested, or a significant importation of Oriental mares (the term used in historic records to refer to Middle East and western Asian breeds including Arab, Akhal-Teke, Barb and Caspian). Instead, we show that Thoroughbred foundation mares had a cosmopolitan European heritage with a far greater contribution from British and Irish Native mares than previously recognized.
Asunto(s)
Cruzamiento , Caballos/genética , Linaje , Animales , ADN Mitocondrial/química , Femenino , Frecuencia de los Genes , Variación Genética , Haplotipos , Irlanda , Masculino , Medio Oriente , Reino UnidoRESUMEN
The giant deer, or 'Irish elk', has featured extensively in debates on adaptation, sexual selection, and extinction. Its huge antlers--the largest of any deer species, living or extinct--formed a focus of much past work. Yet the phylogenetic position of the giant deer has remained an enigma. On the basis of its flattened antlers, the species was previously regarded as closely related to the living fallow deer. Recent morphological studies, however, have challenged that view and placed the giant deer closer to the living red deer or wapiti. Here we present a new phylogenetic analysis encompassing morphological and DNA sequence evidence, and find that both sets of data independently support a sister-group relationship of giant and fallow deer. Our results include the successful extraction and sequencing of DNA from this extinct species, and highlight the value of a joint molecular and morphological approach.
Asunto(s)
Ciervos/clasificación , Ciervos/genética , Fósiles , Filogenia , Animales , Cuernos de Venado/anatomía & histología , Teorema de Bayes , Huesos/anatomía & histología , ADN Mitocondrial/análisis , ADN Mitocondrial/genética , ADN Mitocondrial/aislamiento & purificación , Ciervos/anatomía & histología , Laringe/anatomía & histología , Masculino , Datos de Secuencia Molecular , Polimorfismo Genético/genética , Factores de TiempoRESUMEN
INTRODUCTION: Osteoporosis is highly prevalent in patients with rheumatoid arthritis (RA) and is a frequent cause of fractures, disability, reduced quality of life and increased use of healthcare resources. DISCUSSION: Factors associated with the development of osteoporosis and fractures in patients with RA include disease activity, inflammation, gender, age, low body mass and glucocorticoid exposure. Several processes contribute towards the pathology of RA-associated osteoporosis, and increased osteoclast activation and subsequent bone resorption mediated by pro-inflammatory cytokines are thought to play major roles. Given the key effects of interleukin-6 (IL-6) in both RA and osteoporosis, and its ability to modulate other inflammatory mediators, IL-6 may be an important factor specifically associated with osteoporosis in patients with RA. CONCLUSION: The development of agents that modulate the actions of IL-6 and those of other pro-inflammatory mediators of bone loss may provide alternative osteoporosis management strategies for patients with RA than existing general osteoporosis therapies.
Asunto(s)
Artritis Reumatoide/complicaciones , Interleucina-6/fisiología , Osteoporosis/etiología , Artritis Reumatoide/fisiopatología , Conservadores de la Densidad Ósea/uso terapéutico , Humanos , Mediadores de Inflamación/fisiología , Osteoporosis/tratamiento farmacológico , Osteoporosis/fisiopatología , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVES: People with a diagnosis of psychosis often experience low motivation and reduced activity levels. Autobiographical memory deficits have been identified in people with psychosis and this may limit the role of memory retrieval in supporting motivation. This pilot study adapted a recently developed protocol, Memflex, which aims to enhance autobiographical memory and has shown promise in depression. Our brief intervention targets experiential negative symptoms of psychosis using supported autobiographical memory retrieval. METHOD: A sample of 31 participants with psychosis were recruited from inpatient and community settings and randomised in a 2:1 ratio to either a basic recall control or an enhanced recall intervention group. Participants were asked to generate positive autobiographical memories linked to activities they wish to repeat in the future. The enhanced recall condition received additional prompts from the Memflex protocol, and the basic recall condition received no additional support. RESULTS: The intervention delivered was acceptable (rated >80%) and feasible (94% adherence) to those who took part. Participants were able to generate positive autobiographical memories linked to their goals and experienced appropriate emotions linked to these. The controlled preliminary effect sizes (0.2-0.34) showed encouraging signals for self-efficacy, motivation and a reduction in negative mood. LIMITATIONS: As this was a pilot study with a small sample size between-group tests of statistical significance were not conducted, and therefore findings should be interpreted with caution. CONCLUSIONS: These findings suggest that guided autobiographical memory retrieval may be an effective way tool for targeting motivation in people with psychosis.
Asunto(s)
Memoria Episódica , Recuerdo Mental , Motivación , Trastornos Psicóticos/psicología , Calidad de Vida , Adulto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Proyectos Piloto , Trastornos Psicóticos/terapiaRESUMEN
OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
Asunto(s)
Antirreumáticos/administración & dosificación , Metotrexato/administración & dosificación , Enfermedades Reumáticas/tratamiento farmacológico , Anomalías Inducidas por Medicamentos/etiología , Administración Oral , Antirreumáticos/efectos adversos , Quimioterapia Combinada , Medicina Basada en la Evidencia , Femenino , Ácido Fólico/administración & dosificación , Humanos , Cuidados a Largo Plazo , Masculino , Metotrexato/efectos adversos , Atención Preconceptiva , Factores de RiesgoRESUMEN
Maternally inherited mitochondrial DNA (mtDNA) has been used extensively to determine origin and diversity of taurine cattle (Bos taurus) but global surveys of paternally inherited Y-chromosome diversity are lacking. Here, we provide mtDNA information on previously uncharacterised Eurasian breeds and present the most comprehensive Y-chromosomal microsatellite data on domestic cattle to date. The mitochondrial haplogroup T3 was the most frequent, whereas T4 was detected only in the Yakutian cattle from Siberia. The mtDNA data indicates that the Ukrainian and Central Asian regions are zones where hybrids between taurine and zebu (B. indicus) cattle have existed. This zebu influence appears to have subsequently spread into southern and southeastern European breeds. The most common Y-chromosomal microsatellite haplotype, termed here as H11, showed an elevated frequency in the Eurasian sample set compared with that detected in Near Eastern and Anatolian breeds. The taurine Y-chromosomal microsatellite haplotypes were found to be structured in a network according to the Y-haplogroups Y1 and Y2. These data do not support the recent hypothesis on the origin of Y1 from the local European hybridization of cattle with male aurochsen. Compared with mtDNA, the intensive culling of breeding males and male-mediated crossbreeding of locally raised native breeds has accelerated loss of Y-chromosomal variation in domestic cattle, and affected the contribution of genetic drift to diversity. In conclusion, to maintain diversity, breeds showing rare Y-haplotypes should be prioritised in the conservation of cattle genetic resources.
Asunto(s)
Bovinos/genética , ADN Mitocondrial/genética , Linaje , Cromosoma Y/genética , Animales , Secuencia de Bases , ADN Mitocondrial/análisis , Padre , Femenino , Variación Genética , Haplotipos , Masculino , Datos de Secuencia Molecular , Madres , Filogenia , Homología de Secuencia de Ácido NucleicoAsunto(s)
Epigénesis Genética , Lupus Eritematoso Sistémico/etiología , Microbiota , Animales , Ambiente , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/microbiología , Lupus Eritematoso Sistémico/virología , Factores de RiesgoRESUMEN
Autoimmune diseases are generally more common in women than men; however, there is no simple explanation for this. Sex hormones, especially estrogen (but also prolactin and testosterone), play important roles in these diseases. Estrogens are generally considered to enhance autoimmunity and have multiple effects on the immune system through various cell types and molecular pathways. There is much evidence supporting the role of estrogen in the pathogenesis of systemic lupus erythematosus (SLE): the disease occurs much more frequently in women, especially during the years of child-bearing potential, and commonly flares during pregnancy. The relationship between estrogen and the development of SLE is complex, however. Exogenous estrogens have been historically avoided in women with SLE due to the widely held view that they could activate disease and their use remains controversial. Current evidence from prospective trials suggests that there may be a small increased risk of mild/moderate flares in women with SLE taking hormone replacement therapy (HRT), but the risk of major flare does not appear to be increased. In rheumatoid arthritis, HRT does not appear to be associated with an increased risk of disease flare and may actually improve disease activity. In all individuals with autoimmune disease, the risk of venous thrombosis associated with oral HRT is an important factor that should also be considered.
Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Terapia de Reemplazo de Estrógeno/efectos adversos , Lupus Eritematoso Sistémico , Animales , Artritis Reumatoide/fisiopatología , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/fisiopatología , Estrógenos/efectos adversos , Estrógenos/fisiología , Femenino , Hormonas Esteroides Gonadales/efectos adversos , Hormonas Esteroides Gonadales/fisiología , Hormonas Esteroides Gonadales/uso terapéutico , Humanos , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Embarazo , Receptores de Estrógenos/fisiología , Trombosis de la Vena/inducido químicamenteRESUMEN
Mitochondrial DNA has been the traditional marker for the study of animal domestication, as its high mutation rate allows for the accumulation of molecular diversity within the time frame of domestic history. Additionally, it is exclusively maternally inherited and haplotypes become part of the domestic gene pool via actual capture of a female animal rather than by interbreeding with wild populations. Initial studies of British aurochs identified a haplogroup, designated P, which was found to be highly divergent from all known domestic haplotypes over the most variable portion of the D-loop. Additional analysis of a large and geographically representative sample of aurochs from northern and central Europe found an additional, separate aurochs haplotype, E. Until recently, the European aurochs appeared to have no matrilinear descendants among the publicly available modern cattle control regions sequenced; if aurochs mtDNA was incorporated into the domestic population, aurochs either formed a very small proportion of modern diversity or had been subsequently lost. However, a haplogroup P sequence has recently been found in a modern sample, along with a new divergent haplogroup called Q. Here we confirm the outlying status of the novel Q and E haplogroups and the modern P haplogroup sequence as a descendent of European aurochs, by retrieval and analysis of cytochrome b sequence data from twenty ancient wild and domesticated cattle archaeological samples.
Asunto(s)
Bovinos/genética , Citocromos b/genética , Evolución Molecular , Fósiles , Filogenia , Animales , Secuencia de Bases , Análisis por Conglomerados , Alemania , Datos de Secuencia Molecular , Análisis de Secuencia de ADN/veterinaria , Eslovaquia , Reino UnidoRESUMEN
To obtain more knowledge of the origin and genetic diversity of domestic horses in China, this study provides a comprehensive analysis of mitochondrial DNA (mtDNA) D-loop sequence diversity from nine horse breeds in China in conjunction with ancient DNA data and evidence from archaeological and historical records. A 247-bp mitochondrial D-loop sequence from 182 modern samples revealed a total of 70 haplotypes with a high level of genetic diversity. Seven major mtDNA haplogroups (A-G) and 16 clusters were identified for the 182 Chinese modern horses. In the present study, nine 247-bp mitochondrial D-loop sequences of ancient remains of Bronze Age horse from the Chifeng region of Inner Mongolia in China (c. 4000-2000a bp) were used to explore the origin and diversity of Chinese modern horses and the phylogenetic relationship between ancient and modern horses. The nine ancient horses carried seven haplotypes with rich genetic diversity, which were clustered together with modern individuals among haplogroups A, E and F. Modern domestic horse and ancient horse data support the multiple origins of domestic horses in China. This study supports the argument that multiple successful events of horse domestication, including separate introductions of wild mares into the domestic herds, may have occurred in antiquity, and that China cannot be excluded from these events. Indeed, the association of Far Eastern mtDNA types to haplogroup F was highly significant using Fisher's exact test of independence (P = 0.00002), lending support for Chinese domestication of this haplogroup. High diversity and all seven mtDNA haplogroups (A-G) with 16 clusters also suggest that further work is necessary to shed more light on horse domestication in China.