RESUMEN
BACKGROUND: Induced abortion is one of the most common gynecological procedures in the world, with as many as three in every ten pregnancies ending in abortion. It, however, remains controversial. The objective of this scoping review was to explore and map existing literature on the experiences of those who provide abortion care. METHODS AND FINDINGS: This exploratory review followed the Levac et al. guidelines and was reported in accordance with the PRISMA-ScR checklist. CINAHL, Cochrane, EMBASE, PsycInfo, PubMed, and Web of Science were used to identify peer-reviewed, original research articles published on providers' experience of abortion. We identified 106 relevant studies, which include a total sample of 4,250 providers from 28 countries and six continents. Most of the studies were qualitative (n = 83), though quantitative (n = 15) and mixed methods (n = 8) studies were also included. We identified two overarching themes: (1) Providers' experiences with abortion stigma and (2) Providers' reflections on their abortion work. Our findings suggest that providers from around the world experience challenges within society and their communities and workplaces which reinforce the stigmatization and marginalization of abortion and pose questions about the morality of this work. Most, however, are proud of their work, believe abortion care to be socially important and necessary, and remain committed to the provision of care. CONCLUSIONS: The findings of this review provide a comprehensive overview on the known experiences of providing abortion care. It is a key point of reference for international providers, researchers, and advocates to further this area of research or discussion in their own territories. The findings of this review will inform future work on how to support providers against stigmatization and will offer providers the chance to reflect on their own experiences.
Asunto(s)
Aborto Inducido , Personal de Salud , Humanos , Aborto Inducido/psicología , Femenino , Embarazo , Personal de Salud/psicología , Estigma Social , Actitud del Personal de SaludRESUMEN
BACKGROUND: Despite being one of the most common gynecological procedures in the world, abortion care remains highly stigmatized. Internationally, providers have noted negative impacts related to their involvement in the services, and abortion care has been described as "dirty work." Though much of the existing research focuses on the challenges of providing, many have also highlighted the positive aspects of working in abortion care. Despite the steadily increasing interest in this area over the past decade, however, no one has sought to systematically review the literature to date. OBJECTIVE: The aim of this review is to systematically explore published studies on the experiences of abortion care providers to create a narrative review on the lived experience of providing abortion care, reflecting on what is already known and what areas require further exploration. METHODS: This review will be conducted according to the framework outlined by Levac et al, which expanded on the popular Arksey and O'Malley framework. We will systematically search for peer-reviewed articles in 6 electronic databases: CINAHL, the Cochrane Library, EMBASE, PsycInfo, PubMed, and Web of Science. Following a pilot exercise, we devised a search strategy to identify relevant studies. In this protocol, we outline how citations will be assessed for eligibility and what information will be extracted from the included articles. We also highlight how this information will be combined in the review. RESULTS: As of December 2021, at the time of writing, we have searched for articles in the electronic databases and identified 6624 unique citations. We intend to fully assess these citations for eligibility by the end of January 2022, chart and analyze data from the eligible citations by the end of March 2022, and submit a journal article for peer review by late spring 2022. CONCLUSIONS: The findings of this review will provide a comprehensive overview on the known experiences of providing abortion care. We also anticipate that the findings will identify aspects of care and experiences that are not reflected in the available literature. We will disseminate the results via a publication in a peer-reviewed academic journal and by presenting the findings at conferences in the areas of abortion care, obstetrics, and midwifery. As this review is a secondary analysis of published articles, ethical approval was not required. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35481.
RESUMEN
BACKGROUND: Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy [anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4)], but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy. PATIENTS AND METHODS: Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD-1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined. RESULTS: One hundred and eighteen patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4), with an estimated incidence of 5.3% (95% confidence interval 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53 months). Eighty-seven patients (74%) were on anti-PD-1 at irAE onset, 15 patients (12%) were <3 months from the last dose and 16 patients (14%) were >3 months from the last dose of anti-PD-1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥grade 3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD-1 and a multiple-organ irAE with onset 11 months after ceasing anti-PD-1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%). CONCLUSIONS: Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAEs, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD-1. The risk of delayed irAE should be considered when deciding the duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.
Asunto(s)
Melanoma , Neumonía , Humanos , Factores Inmunológicos , Inmunoterapia/efectos adversos , Melanoma/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Aim To assess breastfeeding intention, initiation and duration up to three months postnatal and associated factors. Methods Secondary data from 131 healthy pregnant women participating in an RCT in a Dublin hospital who recorded intention to breastfeed were included. Demographic and breastfeeding data were collected. Results Of the 131 women, 91.6% (n=120) reported intending to breastfeed. 91.7% of those subsequently initiated breastfeeding (n=110/120). Of those intending to breastfeed, 78.9% (n=86/109) and 68.9% (n=73/106) remained breastfeeding at one and three months postnatal respectively. Higher education (p<0.05) and lower BMI (p<0.05) were significantly associated with initiation and duration of breastfeeding. Ethnicity, age, parity or mode of delivery were not significantly associated with breastfeeding. Conclusion Many factors are associated with breastfeeding intention and duration including education and BMI. It is important to develop tailored support measures to encourage initiation and continuation of breastfeeding.
RESUMEN
Mycoplasmas are simple, but successful parasites that have the smallest genome of any free-living cell and are thought to have a highly streamlined cellular metabolism. Here, we have undertaken a detailed metabolomic analysis of two species, Mycoplasma bovis and Mycoplasma gallisepticum, which cause economically important diseases in cattle and poultry, respectively. Untargeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses of mycoplasma metabolite extracts revealed significant differences in the steady-state levels of many metabolites in central carbon metabolism, while 13C stable isotope labeling studies revealed marked differences in carbon source utilization. These data were mapped onto in silico metabolic networks predicted from genome wide annotations. The analyses elucidated distinct differences, including a clear difference in glucose utilization, with a marked decrease in glucose uptake and glycolysis in M. bovis compared to M. gallisepticum, which may reflect differing host nutrient availabilities. The 13C-labeling patterns also revealed several functional metabolic pathways that were previously unannotated in these species, allowing us to assign putative enzyme functions to the products of a number of genes of unknown function, especially in M. bovis. This study demonstrates the considerable potential of metabolomic analyses to assist in characterizing significant differences in the metabolism of different bacterial species and in improving genome annotation. IMPORTANCE Mycoplasmas are pathogenic bacteria that cause serious chronic infections in production animals, resulting in considerable losses worldwide, as well as causing disease in humans. These bacteria have extremely reduced genomes and are thought to have limited metabolic flexibility, even though they are highly successful persistent parasites in a diverse number of species. The extent to which different Mycoplasma species are capable of catabolizing host carbon sources and nutrients, or synthesizing essential metabolites, remains poorly defined. We have used advanced metabolomic techniques to identify metabolic pathways that are active in two species of Mycoplasma that infect distinct hosts (poultry and cattle). We show that these species exhibit marked differences in metabolite steady-state levels and carbon source utilization. This information has been used to functionally characterize previously unknown genes in the genomes of these pathogens. These species-specific differences are likely to reflect important differences in host nutrient levels and pathogenic mechanisms.
RESUMEN
Introduction: atrial fibrillation (AF) and orthostatic hypotension (OH) share common risk factors such as age, hypertension and cardiovascular (CV) disease. The autonomic nervous system (ANS) also plays a role in the pathogenesis of both AF and OH. The aim of this study is to assess whether individuals with AF are more likely to have OH than those without AF. Methods: data from wave 1 of The Irish Longitudinal Study on Ageing were used. Beat-to-beat blood pressure was measured during active stand lasting 110 s. OH, defined as a drop in systolic blood pressure (SBP) ≥20 mmHg or a drop in diastolic blood pressure ≥10 mmHg at 30, 60 and 90 s was assessed. Initial OH (IOH) was assessed as a drop in SBP ≥40 mmHg or a drop in diastolic BP≥20 mmHg. Results: in total 4,408 participants aged ≥50 had active stand and electrocardiogram data suitable for analysis. AF was identified in 101 of these. Logistic regression found participants with AF were more likely to have OH at 30 (odds ratio (OR) 1.95, 95% confidence interval (CI) 1.24-3.06) and 60 (OR 2.13, 95% CI 1.18-3.87) seconds, and IOH (OR 1.81, 95% CI 1.21-2.70). The association between IOH and OH at 30 s remained significant following adjustment for confounders (age, sex, baseline HR, education, BP, smoking, frailty, beta blocker (BB) use, anti-hypertensive use (excluding BBs) and number of CV conditions). Conclusion: OH is more common in individuals with AF, this may reflect the role of the ANS in both AF and OH.
Asunto(s)
Envejecimiento , Fibrilación Atrial/epidemiología , Hipotensión Ortostática/epidemiología , Factores de Edad , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea , Distribución de Chi-Cuadrado , Electrocardiografía , Femenino , Frecuencia Cardíaca , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/fisiopatología , Irlanda/epidemiología , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Prospectivos , Factores de RiesgoRESUMEN
Background: Very late diagnosis of HIV is a serious public health issue. We used serious incident reporting (SIR) to identify and address reasons for late diagnoses across the patient pathway. Methods: Cases of very late HIV diagnosis were reported via SIR in two 6-month batches between 2011 and 2012 in Bournemouth, Poole and Bristol. Case notes were reviewed for missed opportunities for earlier diagnosis using a root-cause analysis tool. Results: A total of 33 patients (aged 30-67 years, 66% male) were diagnosed very late. Although the majority were white British (n = 17), Black African (n = 9) and Eastern European (n = 4) ethnicities were over-represented. Twenty-four (73%) patients had clinical indicator conditions for HIV, 30 (91%) had a risk factor for HIV acquisition, with 13 (39%) having 2 or more (men-who-have-sex-with-men (n = 11), partner HIV positive (n = 11), from high-prevalence area (n = 12)). Actions resulting from SIR included increasing awareness of indicator conditions, HIV education days within primary care, and initiatives to increase testing within hospital specialities. Conclusions: SIR allowed identification of reasons for very late HIV diagnosis and provided an impetus for initiatives to address them. SIR may be part of an effective strategy to prevent late diagnosis of HIV which would have important benefits for individual and population health.
Asunto(s)
Diagnóstico Tardío/prevención & control , Infecciones por VIH/diagnóstico , Adulto , Anciano , Inglaterra , Femenino , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Prevalencia , Práctica de Salud PúblicaRESUMEN
Growing evidence highlights a role for mitochondrial dysfunction and oxidative stress as underlying contributors to Parkinson's disease (PD) pathogenesis. DJ-1 (PARK7) is a recently identified recessive familial PD gene. Its loss leads to increased susceptibility of neurons to oxidative stress and death. However, its mechanism of action is not fully understood. Presently, we report that DJ-1 deficiency in cell lines, cultured neurons, mouse brain and lymphoblast cells derived from DJ-1 patients display aberrant mitochondrial morphology. We also show that these DJ-1-dependent mitochondrial defects contribute to oxidative stress-induced sensitivity to cell death since reversal of this fragmented mitochondrial phenotype abrogates neuronal cell death. Reactive oxygen species (ROS) appear to play a critical role in the observed defects, as ROS scavengers rescue the phenotype and mitochondria isolated from DJ-1 deficient animals produce more ROS compared with control. Importantly, the aberrant mitochondrial phenotype can be rescued by the expression of Pink1 and Parkin, two PD-linked genes involved in regulating mitochondrial dynamics and quality control. Finally, we show that DJ-1 deficiency leads to altered autophagy in murine and human cells. Our findings define a mechanism by which the DJ-1-dependent mitochondrial defects contribute to the increased sensitivity to oxidative stress-induced cell death that has been previously reported.
Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/deficiencia , Péptidos y Proteínas de Señalización Intracelular/genética , Mitocondrias/genética , Mitocondrias/patología , Proteínas Oncogénicas/deficiencia , Proteínas Oncogénicas/genética , Enfermedad de Parkinson/genética , Acetilcisteína/farmacología , Animales , Autofagia/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Muerte Celular/efectos de los fármacos , Línea Celular , Humanos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Proteínas Mutantes/metabolismo , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Neostriado/patología , Neostriado/ultraestructura , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Neuronas/ultraestructura , Enfermedad de Parkinson/patología , Peroxirredoxinas , Fenotipo , Proteína Desglicasa DJ-1 , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Databases of mutations causing Mendelian disease play a crucial role in research, diagnostic and genetic health care and can play a role in life and death decisions. These databases are thus heavily used, but only gene or locus specific databases have been previously reviewed for completeness, accuracy, currency and utility. We have performed a review of the various general mutation databases that derive their data from the published literature and locus specific databases. Only two--the Human Gene Mutation Database (HGMD) and Online Mendelian Inheritance in Man (OMIM)--had useful numbers of mutations. Comparison of a number of characteristics of these databases indicated substantial inconsistencies between the two databases that included absent genes and missing mutations. This situation strengthens the case for gene specific curation of mutations and the need for an overall plan for collection, curation, storage and release of mutation data.
Asunto(s)
Bases de Datos Genéticas , Mutación , Genoma Humano , HumanosRESUMEN
Intimal hyperplasia (IH) development is a primary cause of failure of reconstructive bypass surgery. While the exact mechanism by which IH initiates and proliferates has yet to be fully elucidated, it is clear that the abnormal haemodynamics present in the downstream graft/artery junction are intrinsic in its development. Mass transport disturbances owing to abnormal haemodynamics have been associated with atherogenesis and it is for this reason that an investigation into transport of platelet-derived growth factor (PDGF), a known promoter of the intimal hyperplastic response, at the downstream graft/artery junction was carried out. A steady flow analysis in a three-dimensional, idealized, downstream graft/artery junction was carried out using commercial computational fluid dynamics software. It was found that there is a two-and-half fold increase in the transport of PDGF to the artery wall at the bed of the junction when compared with an idealized, healthy artery. The presence of secondary flows in the downstream arterial section also leads to large disturbances in mass transport. It was concluded that PDGF transport in the downstream graft/artery junction tends to be highly disturbed and that there may be a role of this disturbance in the initiation and subsequent development of distal anastomotic intimal hyperplasia.
Asunto(s)
Arterias/fisiopatología , Arterias/cirugía , Velocidad del Flujo Sanguíneo , Modelos Cardiovasculares , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Trasplantes , Procedimientos Quirúrgicos Vasculares/métodos , Anastomosis Quirúrgica/métodos , Animales , Transporte Biológico Activo , Presión Sanguínea , Simulación por Computador , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Prospective longitudinal studies now indicate that cognitive dysfunction following coronary artery bypass surgery (CABG) is both common and persistent. This dysfunction is due in part to the inflammatory response and cerebral ischaemia-reperfusion, with nitric oxide (NO) as an important mediator of both. We hypothesized that a clinically significant association exists between plasma concentrations of nitrate/nitrite (NO3-/NO2-) and cognitive dysfunction after CABG. METHODS: Cognitive assessment was performed on 36 adult patients the day before CABG, on the fourth postoperative day and 3 months postoperatively. Patient spouses (n = 10) were also studied. RESULTS: A new cognitive deficit was present in 22/36 (62%) 4 days postoperatively and in 16/35 (49%) of patients, 3 months postoperatively. Patients who had cognitive dysfunction 3 months postoperatively were more likely to have cognitive dysfunction and increased plasma NO3-/NO2- concentrations compared to the non-deficit group preoperatively (22.6 (9.2) vs. 27.6 (8.4)) (P = 0.002). Plasma NOx (NO3- plus NO2-) concentrations were greater in patients with cognitive dysfunction 3 months postoperatively, 2 h (24.2 (6.3) vs. 19.1 (5.2)) (P = 0.002), and 12 h postoperatively (24.8 (7.6) vs. 18.8 (5.6)) (P = 0.001). There was, however, a time course similarity in NOx elevations for both deficit and non-deficit groups. CONCLUSIONS: Perioperative plasma NOx concentrations do not serve as an effective biomarker of cognitive deficit after CABG.
Asunto(s)
Puente Cardiopulmonar/efectos adversos , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/etiología , Óxido Nítrico/sangre , Complicaciones Posoperatorias/sangre , Adulto , Afecto/fisiología , Anciano , Biomarcadores , Trastornos del Conocimiento/psicología , Delirio/inducido químicamente , Delirio/psicología , Depresión/diagnóstico , Depresión/psicología , Circulación Extracorporea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Miocardio/patología , Pruebas Neuropsicológicas , Nitratos/sangre , Donantes de Óxido Nítrico/uso terapéutico , Nitritos/sangre , Complicaciones Posoperatorias/psicología , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Tramadol has been administered peripherally to prolong analgesia after brachial plexus and neuraxial blocks. Our aim was to evaluate the systemic and perineural effects of tramadol as an analgesic adjunct to psoas compartment block (PCB) with levobupivacaine. METHODS: In a randomized, prospective, double-blinded trial, 60 patients (ASA I-III), aged 49-88 yr, undergoing primary total hip or knee arthroplasty underwent PCB and subsequent bupivacaine spinal anaesthesia. Patients were randomized into three groups. Each patient received PCB with levobupivacaine 0.5%, 0.4 ml kg(-1). The control group (group L, n=21) received i.v. saline, the systemic tramadol group (group IT, n=19) received i.v. tramadol 1.5 mg kg(-1) and the perineural tramadol group (group T, n=20) received i.v. saline and PCB with tramadol 1.5 mg kg(-1). Postoperatively patients received regular paracetamol 6-hourly and diclofenac sodium 12-hourly. Time to first morphine analgesia, 24-hour morphine consumption, sensory block, pain and sedation scores and haemodynamic parameters were recorded. RESULTS: Time (h) to first morphine analgesia was similar in the three groups [mean (SD)]: group L, 11.2 (6.6); group T, 14.5 (8.0); group IT, 14.6 (6.8); P=0.35. Twenty-four-hour cumulative morphine (mg) consumption was also similar in the three groups [group L, 21.9 (10.1); group T, 19.8 (6.7), group IT, 16.5 (9.5)], as were durations of sensory and motor block. There were no differences in the incidence of adverse effects except that patients in group IT were more sedated at 14 h than group L (P=0.02). CONCLUSION: We conclude that our data do not support a clinically important local anaesthetic or peripheral analgesic effect of tramadol as adjunct to PCB with levobupivacaine 0.5%.
Asunto(s)
Analgésicos Opioides , Anestésicos Locales , Bupivacaína , Bloqueo Nervioso/métodos , Tramadol , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Bupivacaína/análogos & derivados , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Levobupivacaína , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Dimensión del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Músculos Psoas/inervaciónRESUMEN
BACKGROUND AND OBJECTIVES: Teaching is an important responsibility of non-consultant hospital doctors. In Ireland, specialist registrars (SpRs) in anaesthesia are contractually obliged to teach medical students, other doctors and nurses. Both medical students and fellow non-consultant hospital doctors attribute between 30 and 40% of their knowledge gain to non-consultant hospital doctors. METHODS: We carried out a confidential telephone survey of anaesthetic SpRs in Ireland regarding their current teaching practices and the perceptions of their role as undergraduate teachers. All the SpRs currently working in clinical practice in Ireland were eligible. RESULTS: Fifty-five of the 79 (70%) SpRs responded to the questionnaire. Only 7 (12.7%) of the respondents said they had been well trained as a teacher. The majority of the respondents stated that they would attend a learning-to-teach course/workshop if one was available, and felt that such a course would improve their ability as a teacher. Only 8 (14.5%) agreed that adequate emphasis is placed on commitment to teaching in the assessment of SpRs, both by individual departments and by the College of Anaesthetists. Anaesthetic SpRs in Ireland spend a considerable amount of time each day teaching undergraduate medical students, the majority (68.9%) stated that they had inadequate time to prepare for teaching. CONCLUSION: The majority of the respondents stated that they enjoy teaching, feel that they play an important role in undergraduate teaching but have inadequate time to prepare for teaching. An adequate emphasis is not placed on their commitment to teaching.
Asunto(s)
Anestesiología/educación , Enseñanza , Adulto , Actitud del Personal de Salud , Recolección de Datos , Educación de Pregrado en Medicina , Femenino , Humanos , Irlanda , Masculino , Cuerpo Médico de HospitalesRESUMEN
Expression of the transcription factor c-Jun is induced in neurons of the central nervous system (CNS) in response to injury. Mechanical transection of the nigrostriatal pathway at the medial forebrain bundle (MFB) results in the delayed retrograde degeneration of the dopamine neurons in the substantia nigra pars compacta (SNc) and induces protracted expression and phosphorylation of c-Jun. However, the role of c-Jun after axotomy of CNS neurons is unclear. Here, we show that adenovirus-mediated expression of a dominant negative form of c-Jun (Ad.c-JunDN) inhibited axotomy-induced dopamine neuron death and attenuated phosphorylation of c-Jun in nigral neurons. Ad.c-JunDN also delayed the degeneration of dopaminergic nigral axons in the striatum after MFB axotomy. Taken together, these findings suggest that activation of c-Jun mediates the loss of dopamine neurons after axotomy injury.
Asunto(s)
Apoptosis/fisiología , Axotomía , Dopamina/fisiología , Proteínas Proto-Oncogénicas c-jun/fisiología , Animales , Supervivencia Celular/fisiología , Cromatografía Líquida de Alta Presión , Inmunohistoquímica , Masculino , Fosforilación , Proteínas Proto-Oncogénicas c-jun/química , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratas , Ratas Wistar , Serina/metabolismoRESUMEN
In September 1997 screening for Down syndrome using first trimester ultrasound to measure nuchal translucency, with risk estimation by the software program developed in the United Kingdom by the Fetal Medicine Foundation, was introduced in Newcastle, New South Wales. In the first 2,000 such risk estimations 134 women (6.7 %) were screen positive (with a risk of greater than 1 in 300 at that gestation for Trisomy 21). In the first 1,000 of these 2,000 fetuses delivered thus far there were 8 cases of Trisomy 21, 2 of Trisomy 18 and 1 of 47 XXX. Nine of these 11 were screen positive, the only false negative results being for 2 cases of Trisomy 21. The detection rate for Trisomy 21 was 6 out of 8 (75%) and for every case of Trisomy 21 (Down Syndrome) detected by this process, 11.3 invasive tests would have been needed to make that diagnosis in a screen positive woman.
Asunto(s)
Síndrome de Down/diagnóstico por imagen , Síndrome de Down/epidemiología , Cuello/diagnóstico por imagen , Programas Informáticos , Ultrasonografía Prenatal/instrumentación , Síndrome de Down/diagnóstico , Desarrollo Embrionario y Fetal/fisiología , Diseño de Equipo , Femenino , Humanos , Tamizaje Masivo/instrumentación , Tamizaje Masivo/métodos , Nueva Gales del Sur/epidemiología , Embarazo , Primer Trimestre del Embarazo , Atención Prenatal/métodos , Medición de Riesgo , Sensibilidad y Especificidad , Sociedades Médicas , Ultrasonografía Prenatal/métodos , Reino UnidoRESUMEN
Recombinant adenovirus vectors have provided a major advance in gene delivery systems for post-mitotic neurons. However, the use of these first generation vectors has been limited due to the onset of virally mediated effects on cellular function and viability. In the present study we have used primary cultures of cerebellar granule neurons to examine the efficacy and cytotoxic effects of a helper-dependent adenovirus vector (hdAd) in comparison with a first generation vector. Our results demonstrate that the hdAd system provides equally efficient infectivity with significantly reduced toxicity in comparison to first generation vectors. Neurons transduced with a high titre of a first generation vector exhibited a time-dependent shut down in global protein synthesis and impaired physiological function as demonstrated by a loss of glutamate receptor responsiveness. This was followed by an increase in the fraction of TUNEL-positive cells and a loss of neuronal survival. In contrast, hdAds could be used at titres that transduce >85% of neurons with little cytotoxic effect: cellular glutamate receptor responses and rates of protein synthesis were indistinguishable from uninfected controls. Furthermore, cell viability was not significantly affected for at least 7 days after infection. At excessive viral titres, however, infection with hdAd did cause moderate but significant changes in cell function and viability in primary neuronal cultures. Thus, while these vectors are remarkably improved over first generation vectors, these also have limitations with respect to viral effects on cellular function and viability. Gene Therapy (2000) 7, 1200-1209.
Asunto(s)
Adenoviridae/genética , Vectores Genéticos/uso terapéutico , Neuronas , Animales , Supervivencia Celular , Células Cultivadas , Vectores Genéticos/efectos adversos , Ratones , N-Metilaspartato/metabolismo , Neuronas/metabolismo , Neuronas/virología , Biosíntesis de Proteínas , Transducción Genética/genéticaRESUMEN
The tumor suppressor, retinoblastoma (Rb), is involved in both terminal mitosis and neuronal differentiation. We hypothesized that activation of the Rb pathway would induce cell cycle arrest in primary neural precursor cells, independent of the proposed function of cyclin-dependent kinases 4/6 (CDK4/6) to sequester the CIP/KIP CDK inhibitors (CKIs) p21 and p27 from CDK2. We expressed dominant negative adenovirus mutants of CDKs 2, 4, and 6 (dnCDK2, dnCDK4, and dnCDK6) in neural progenitor cells derived from E12.5 wild type and Rb-deficient mouse embryos. In contrast to previous studies, our results demonstrate that in addition to dnCDK2, the dnCDK4/6 mutants can induce growth arrest. Moreover, the dnCDK4/6-mediated inhibition is Rb-dependent. The dnCDK2 partially inhibited cell growth in Rb-deficient cells, suggesting that CDK2 may have additional targets. A previously proposed function of CDK4/6 is CKI sequestration, thereby preventing the resulting inhibition of CDK2, believed to be the key regulator of cell cycle. However, our immunoprecipitations revealed that the dominant negative CDK mutants could arrest cell growth despite their interaction with p21 and p27. Taken together, our results demonstrate that both CDK2 and CDK4/6 are crucial for cell cycle regulation. Furthermore, our data underscore the importance of the Rb regulatory pathway in neuronal development and cell cycle regulation, independent of CKI sequestration.
Asunto(s)
Quinasas CDC2-CDC28 , Quinasas Ciclina-Dependientes/fisiología , Neuronas/fisiología , Proteínas Serina-Treonina Quinasas/fisiología , Proteínas Proto-Oncogénicas , Proteína de Retinoblastoma/fisiología , Células Madre/fisiología , Animales , Ciclo Celular , Diferenciación Celular , Quinasa 2 Dependiente de la Ciclina , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/fisiología , Ratones , Ratones TransgénicosRESUMEN
OBJECTIVES: To assess the efficacy of an ultrasound scan at the first antenatal visit. DESIGN: Randomised clinical trial. SETTING: Women's and Children's tertiary level hospital, Adelaide, Australia. POPULATION: Six hundred and forty-eight women attending for their first antenatal visit at less than 17 weeks of gestation who had no previous ultrasound scan in the pregnancy, who were expected to give birth at the hospital, and for whom there was no indication for an ultrasound at their first visit. METHODS: Eligible consenting women were enrolled by telephone randomisation into either the ultrasound at first visit group, who had an ultrasound at the time of their first antenatal visit, or the control group in whom no ultrasound assessment was done at their first antenatal visit. Both groups of women completed a questionnaire at the end of the first visit on their feelings towards the pregnancy and anxiety levels. Data were collected on details of any ultrasound assessments, including the 18 to 20 weeks morphology scan, and pregnancy outcome. All primary analyses were on an intention-to-treat basis. MAIN OUTCOME MEASURES: The number of women who needed adjustment in dates of 10 days or more on the basis of their 18 to 20 weeks ultrasound morphology scan, who were booked for their morphology scan at sub-optimal gestations, who had a repeat of their maternal serum screening test, or who felt worried about their pregnancy at the end of the first antenatal visit. RESULTS: Fewer women (9%) in the ultrasound at first visit group needed adjustment of their expected date of delivery as a result of the 18 to 20 week ultrasound, compared with 18% of women in the control group (RR 0.52, 95% CI 0.34-0.79; P = 0.002). The number of women who had the 18 to 20 week ultrasound assessment timed suboptimally was similar to that in the control group (16% vs. 21%), as was the number of women who had a repeat blood sample taken for maternal serum screening (6% vs. 6%). Fewer women in the ultrasound at first visit group reported feeling worried about their pregnancy (RR 0.80, 95% CI 0.65-0.99; P = 0.04) or not feeling relaxed about their pregnancy (RR 0.73, 95% CI 0.56-0.96; P = 0.02), compared with women in the control group. CONCLUSIONS: A routine ultrasound assessment for dating offered to women at the first antenatal visit provides more precise estimates of gestational age and reduces the need to adjust the estimate of the date of delivery in mid-gestation. Women who had an ultrasound at the first visit reported more positive feelings about their pregnancy, compared with women in the control group at that time.