Can the biology of VEGF and haem oxygenases help solve pre-eclampsia?

Pre-eclampsia, a pregnancy-specific multi-organ syndrome characterized by widespread endothelial damage, is a new risk factor for cardiovascular disease. No therapies exist to prevent or treat this condition, even to achieve a modest improvement in pregnancy length or birth weight. Co-administration of soluble VEGFR-1 [VEGF (vascular endothelial growth factor) receptor-1; more commonly known as sFlt-1 (soluble Fms-like tyrosine kinase-1)] and sEng (soluble endoglin) to pregnant rats elicits severe pre-eclampsia-like symptoms. These two anti-angiogenic factors are increased dramatically prior to the clinical onset of pre-eclampsia and are quite possibly the 'final common pathway' responsible for the accompanying signs of hypertension and proteinuria as they can be reversed by VEGF administration in animal models. HO-1 (haem oxygenase-1), an anti-inflammatory enzyme, and its metabolite, CO (carbon monoxide), exert protective effects in several organs against oxidative stimuli. In a landmark publication, we showed that the HO-1 pathway inhibits sFlt-1 and sEng in cultured cells and human placental tissue explants. Both CO and NO (nitric oxide) promote vascular homoeostasis and vasodilatation, and activation of VEGFR-1 or VEGFR-2 induced eNOS (endothelial nitric oxide synthase) phosphorylation, NO release and HO-1 expression. Our studies established the HO-1/CO pathway as a negative regulator of cytokine-induced sFlt-1 and sEng release and eNOS as a positive regulator of VEGF-mediated vascular morphogenesis. These findings provide compelling evidence for a protective role of HO-1 in pregnancy and identify it as a target for the treatment of pre-eclampsia. Any agent that is known to up-regulate HO-1, such as statins, may have potential as a therapy. Any intervention achieving even a modest prolongation of pregnancy or amelioration of the condition could have a significant beneficial health impact worldwide.

The continuum of psychotic symptoms in the general population:a cross-national study

OBJECTIVE: To identify the cross-national prevalence of psychotic symptoms in the general population and to analyze their impact on health status. METHOD: The sample was composed of 256,445 subjects (55.9% women), from nationally representative samples of 52 countries worldwide participating in the World Health Organization's World Health Survey. Standardized and weighted prevalence of psychotic symptoms were calculated in addition to the impact on health status as assessed by functioning in multiple domains. RESULTS: Overall prevalences for specific symptoms ranged from 4.80% (SE = 0.14) for delusions of control to 8.37% (SE = 0.20) for delusions of reference and persecution. Prevalence figures varied greatly across countries. All symptoms of psychosis produced a significant decline in health status after controlling for potential confounders. There was a clear change in health impact between subjects not reporting any symptom and those reporting at least one symptom (effect size of 0.55). CONCLUSIONS: The prevalence of the presence of at least one psychotic symptom has a wide range worldwide varying as much as from 0.8% to 31.4%. Psychotic symptoms signal a problem of potential public health concern, independent of the presence of a full diagnosis of psychosis, as they are common and are related to a significant decrement in health status. The presence of at least one psychotic symptom is related to a significant poorer health status, with a regular linear decrement in health depending on the number of symptoms.

Depresión subclínica en España:prevalencia e impacto sobre la salud

INTRODUCCIÓN: La depresión subclínica es una condición prevalente que presenta importantes implicaciones para el funcionamiento y el bienestar de los pacientes. Sin embargo, faltan estudios que operativicen su definición y que profundicen en su significación clínica y su impacto en la salud. El presente trabajo analiza el impacto de la depresión subclínica sobre un indicador de salud compuesto por ocho dominios de funcionamiento, y su prevalencia en la población española. MÉTODO: La muestra se ha extraído de la base de datos de la Encuesta Mundial de Salud de la OMS, seleccionando las respuestas para España de personas con depresión subclínica y sin depresión. RESULTADOS: Controlando la interacción de las distintas variables demográficas, ser mujer resulta ser el único predictor significativo para la presencia de depresión subclínica. Un peor estado de salud se asocia significativamente con presentar depresión subclínica, ser mujer, tener una edad elevada, un bajo nivel de ingresos, un menor número de años de educación formal y ser viudo. La disminución resulta significativa en los ocho dominios de funcionamiento que conforman el índice. CONCLUSIONES: Se pone de manifiesto la necesidad de conceptualizar mejor la naturaleza de la depresión subclínica, profundizando en la línea de recientes propuestas que abogan por una definición basada en su significación clínica más que en el número de síntomas depresivos, con el objetivo de no patologizar el sufrimiento humano y el malestar inherente a muchas situaciones vitales. INTRODUCTION: Subclinical depression is a prevalent condition with important implications for patients' functioning and wellbeing. However, there is a lack of studies operationalising its definition and studying its clinical significance and health impact in depth. This work analyses subclinical depression impact on a health satus score derived from eight heath domains, and its prevalence in Spanish population. METHODS: The sample was selected from World Health Survey database, choosing the answers for Spain of people with a dignosis of subclinical depression and no depressive disorders. RESULTS: Controlling the interaction of the different demographic variables, being female was the only significant predictor for the presence of subclinical depression. A worse health status is associated with subclinical depression, being female, a higher age, lower incomes, less years of formal education and being widowed. The decrease is significant in the eight health domains composing the score. CONCLUSIONS: The necessity of a better conceptualization of the nature of clinical depression is highlighted, going in depth in different proposals defending a definition based on clinical signification rather than in the number of depressive symptoms, with the goal of avoiding the pathologization of human suffering and inherent distress to several vital situations.

Community accessibility of health information and the consequent impact for translation into community languages

This paper reports on a research project that investigated the accessibility of health information and the consequent impact for translation into community languages. This is a critical aspect of the mediation of intercultural and interlingual communication in the domain of public health information and yet very little research has been undertaken to address such issues. The project was carried out in collaboration with the New South Wales Multicultural Health Communication Service (MHCS), which provides advice and services to state-based health professionals aiming to communicate with non-English speaking communities. The research employed a mixed-method and action research based approach involving two phases. The primary focus of this paper is to discuss major quantitative findings from the first pilot phase, which indicated that there is much room to improve the way in which health information is written in English for effective community-wide communication within a multilingual society.

Undermining patient and public engagement and limiting its impact:the consequences of the Health and Social Care Act 2012 on collective patient and public involvement

Patient and public involvement has been at the heart of UK health policy for more than two decades. This commitment to putting patients at the heart of the British National Health Service (NHS) has become a central principle helping to ensure equity, patient safety and effectiveness in the health system. The recent Health and Social Care Act 2012 is the most significant reform of the NHS since its foundation in 1948. More radically, this legislation undermines the principle of patient and public involvement, public accountability and returns the power for prioritisation of health services to an unaccountable medical elite. This legislation marks a sea-change in the approach to patient and public involvement in the UK and signals a shift in the commitment of the UK government to patient-centred care. © 2013 John Wiley & Sons Ltd.

The impact of organisational change on health care delivery to the adult mentally ill

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