Dynamic product diversity

The goal of this paper is to study the frequency of new product introductions in monopoly markets where demand is subject to transitory saturation. We focus on those types of goods for which consumers purchase at most one unit of each variety, but repeat purchases in the same product category. The model considers infinitely-lived, forward-looking consumers and firms. We show that the share of potential surplus that a monopolist is able to appropriate increases with the frequency of introduction of new products and the intensity of transitory saturation. If the latter is sufficiently strong then the rate of introduction of new products is higher than socially desirable (excessive dynamic product diversity.)

Involvement of nuclear factor-kappaB in macrophage migration inhibitory factor gene transcription up-regulation induced by interleukin- 1 beta in ectopic endometrial cells.

OBJECTIVE: To investigate the involvement of the nuclear factor (NF)-kappaB in the interleukin (IL)-1 beta-mediated macrophage migration inhibitory factor (MIF) gene activation. DESIGN: Prospective study. SETTING: Human reproduction research laboratory. PATIENT(S): Nine women with endometriotic lesions. INTERVENTION(S): Endometriotic lesions were obtained during laparoscopic surgery. MAIN OUTCOME MEASURE(S): The MIF protein secretion was analyzed by ELISA, MIF mRNA expression by quantitative real-time polymerase chain reaction (PCR), NF-kappaB translocation into the nucleus by electrophoresis mobility shift assay, I kappaB phosphorylation and degradation by Western blot, and human MIF promoter activity by transient cell transfection. RESULT(S): This study showed a significant dose-dependent increase of MIF protein secretion and mRNA expression, the NF-kappaB translocation into the nucleus, I kappaB phosphorylation, I kappaB degradation, and human MIF promoter activity in endometriotic stromal cells in response to IL-1 beta. Curcumin (NF-kappaB inhibitor) significantly inhibited all these IL-1 beta-mediated effects. Analysis of the activity of deletion constructs of the human MIF promoter and a computer search localized two putative regulatory elements corresponding to NF-kappaB binding sites at positions -2538/-2528 bp and -1389/-1380 bp. CONCLUSION(S): This study suggests the involvement of the nuclear transcription factor NF-kappaB in MIF gene activation in ectopic endometrial cells in response to IL-1 beta and identifies a possible pathway of endometriosis-associated inflammation and ectopic cell growth.

Anterior segment granuloma and optic nerve involvement as the presenting signs of systemic sarcoidosis.

PURPOSE: To report a case with anterior and posterior nodules associated with systemic sarcoidosis. METHODS: A patient with decreased vision underwent complete ophthalmologic examination, ultrasound biomicroscopy, fluorescein and indocyanine green (ICG) angiography. RESULTS: The patient presented a nodule of the iris of the OS and of the optic nerves of both eyes. Chest computed tomography and tissue biopsy established the diagnosis. CONCLUSIONS: Fluorescein and ICG angiography are the only objective exams to demonstrate the extent of ocular involvement in a patient with sarcoidosis.

Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP-regulated glycogen metabolism.

We have described previously a transcription-dependent induction of glycogen resynthesis by the vasoactive intestinal peptide (VIP) or noradrenaline (NA) in astrocytes, which is mediated by cAMP. Because it has been postulated that the cAMP-mediated regulation of energy balance in hepatocytes and adipocytes is channeled at least in part through the CCAAT/enhancer binding protein (C/EBP) family of transcription factors, we tested the hypothesis that C/EBP isoforms could be expressed in mouse cortical astrocytes and that their level of expression could be regulated by VIP, by the VIP-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP), or by NA. We report in this study that in these cells, C/EBP beta and C/EBP delta are induced by VIP, PACAP, or NA via the cAMP second-messenger pathway. Induction of C/EBP beta and -delta mRNA by VIP occurs in the presence of a protein synthesis inhibitor. Thus, c/ebp beta and c/ebp delta behave as cAMP-inducible immediate-early genes in astrocytes. Moreover, transfection of astrocytes with expression vectors selectively producing the transcriptionally active form of C/EBP beta, termed liver-enriched transcriptional activator protein, or C/EBP delta enhance the glycogen resynthesis elicited by NA, whereas an expression vector producing the transcriptionally inactive form of C/EBP beta, termed liver-enriched transcriptional inhibitory protein, reduces this resynthesis. These results support the idea that C/EBP beta and -delta regulate gene expression of energy metabolism-related enzymes in astrocytes.

Involvement of environmental mercury and lead in the etiology of neurodegenerative diseases.

The incidence of neurodegenerative disease like Parkinson's disease and Alzheimer's disease (AD) increases dramatically with age; only a small percentage is directly related to familial forms. The etiology of the most abundant, sporadic forms is complex and multifactorial, involving both genetic and environmental factors. Several environmental pollutants have been associated with neurodegenerative disorders. The present article focuses on results obtained in experimental neurotoxicology studies that indicate a potential pathogenic role of lead and mercury in the development of neurodegenerative diseases. Both heavy metals have been shown to interfere with a multitude of intracellular targets, thereby contributing to several pathogenic processes typical of neurodegenerative disorders, including mitochondrial dysfunction, oxidative stress, deregulation of protein turnover, and brain inflammation. Exposure to heavy metals early in development can precondition the brain for developing a neurodegenerative disease later in life. Alternatively, heavy metals can exert their adverse effects through acute neurotoxicity or through slow accumulation during prolonged periods of life. The pro-oxidant effects of heavy metals can exacerbate the age-related increase in oxidative stress that is related to the decline of the antioxidant defense systems. Brain inflammatory reactions also generate oxidative stress. Chronic inflammation can contribute to the formation of the senile plaques that are typical for AD. In accord with this view, nonsteroidal anti-inflammatory drugs and antioxidants suppress early pathogenic processes leading to Alzheimer's disease, thus decreasing the risk of developing the disease. The effects of lead and mercury were also tested in aggregating brain-cell cultures of fetal rat telencephalon, a three-dimensional brain-cell culture system. The continuous application for 10 to 50 days of non-cytotoxic concentrations of heavy metals resulted in their accumulation in brain cells and the occurrence of delayed toxic effects. When applied at non-toxic concentrations, methylmercury, the most common environmental form of mercury, becomes neurotoxic under pro-oxidant conditions. Furthermore, lead and mercury induce glial cell reactivity, a hallmark of brain inflammation. Both mercury and lead increase the expression of the amyloid precursor protein; mercury also stimulates the formation of insoluble beta-amyloid, which plays a crucial role in the pathogenesis of AD and causes oxidative stress and neurotoxicity in vitro. Taken together, a considerable body of evidence suggests that the heavy metals lead and mercury contribute to the etiology of neurodegenerative diseases and emphasizes the importance of taking preventive measures in this regard.

Strategy for personal and public involvement in Health and Social Care research

This report outlines the strategic need for, and benefits of, personal and public involvement to all levels of Health and Social Care Research and Development Division activity.

Neurological conditions: involvement to improve service delivery

A major, ongoing Public Health Agency led consultation exercise has identified 12 recommendations to improve the lives of the 48,000 people, and their carers, who experience neurological conditions across Northern Ireland. These recommendations will form the basis of an action plan to improve service delivery and support for those experiencing a range of conditions, such as epilepsy, Huntington's Disease, Parkinson's Disease, progressive supranuclear palsy (PSP) and multiple sclerosis (MS).The recommendations cover four areas:accurate information and diagnosis;control and choice, particularly self-management and person-centred services;day-to-day living and independence, including finance, employment, social life and ability to get out and about;emotional and psychological impact on individuals and families, eg the support available to deal with stress, fear, frustration, isolation, loss and vulnerability associated with living with a neurological condition.The report was launched at a regional workshop, held in Cookstown (today) and co-ordinated through the Neurological Conditions Network, which was established to develop this work.Speaking before the workshop, Health Minister Edwin Poots said: "Neurological conditions give rise to complex needs, which require support from a wide range of professionals. They also change lives, both for those directly affected and for their families and carers, and it is so important not to lose sight of this if we are to successfully address the challenges in tackling neurological conditions."Last week, I visited the home of Beth McCune, who suffers from motor neurone disease. I was invited to see for myself the daily challenges faced by Beth and her husband and carer, Arthur, and to hear of their experiences. While I was struck by their courage and patience, this visit underlined again for me the severe life-changing impact of the disease."At present, there are some 48,000 people in Northern Ireland living with neurological conditions. It was in recognition of the needs of men and women like Beth that my department requested the establishment of the Neurological Conditions Network and provided the necessary funding to support it."Michelle Tennyson, PHA Assistant Director and Chair of the Neurological Conditions Network, said: "This detailed engagement exercise was undertaken to get the views and quality of life experiences of those affected by these conditions. We tried to ensure everyone who wanted to contribute could, by providing support through helplines, the internet and face-to-face events. I am honoured that so many people have trusted us with their experiences to help us make a difference and was privileged to be invited into the home of Beth and Arthur McCune for the same reason."The recommendations cover a range of conditions and their implementation will need cooperation and action from professionals, service users, voluntary organizations and others, across many sectors and agencies. The network is looking forward to delivering on these challenging new ways of working to improve the lives of all those affected by neurological conditions."The workshop attracted service users and carers along with delegates from across Northern Ireland's community, voluntary and statutory sectors.If you have a neurological condition, or care for someone who does, and want to share your experiences, please go to: www.publichealth.hscni.net/ncnsurveyYou can also contact Julie Mawhinney, Tel: 028 9032 1313.

Effect of angiotensin II and losartan on the phagocytic activity of peritoneal macrophages from Balb/C mice

Angiotensin II (AII), a product of rennin-angiotensin system, exerts an important role on the function of immune system cells. In this study, the effect of AII on the phagocytic activity of mouse peritoneal macrophages was assessed. Mice peritoneal macrophages were cultured for 48 h and the influence of different concentrations of AII (10-14 to 10-7 M) and/or losartan, 10-16 to 10-6 M), an AT1 angiotensin receptor antagonist, on phagocytic activity and superoxide anion production was determined. Dimethylthiazoldiphenyltetrazolium bromide reduction and the nucleic acid content were used to assess the cytotoxicity of losartan. A stimulatory effect on phagocytic activity (P < 0.05) was observed with 10-13 M and 10-12 M AII concentrations. The addition of losartan (up to10-14 M) to the cell cultures blocked (P < 0.001) the phagocytosis indicating the involvement of AT1 receptors. In contrast, superoxide anion production was not affected by AII or losartan. The existence of AT1 and AT2 receptors in peritoneal macrophages was demonstrated by immunofluorescence microscopy. These results support the hypothesis that AII receptors can modulate murine macrophage activity and phagocytosis, and suggest that AII may have a therapeutic role as an immunomodulatory agent in modifying the host resistance to infection.

Involvement of PPAR nuclear receptors in tissue injury and wound repair.

Tissue damage resulting from chemical, mechanical, and biological injury, or from interrupted blood flow and reperfusion, is often life threatening. The subsequent tissue response involves an intricate series of events including inflammation, oxidative stress, immune cell recruitment, and cell survival, proliferation, migration, and differentiation. In addition, fibrotic repair characterized by myofibroblast transdifferentiation and the deposition of ECM proteins is activated. Failure to initiate, maintain, or stop this repair program has dramatic consequences, such as cell death and associated tissue necrosis or carcinogenesis. In this sense, inflammation and oxidative stress, which are beneficial defense processes, can become harmful if they do not resolve in time. This repair program is largely based on rapid and specific changes in gene expression controlled by transcription factors that sense injury. PPARs are such factors and are activated by lipid mediators produced after wounding. Here we highlight advances in our understanding of PPAR action during tissue repair and discuss the potential for these nuclear receptors as therapeutic targets for tissue injury.

Involvement of central nervous system in the schistosomiasis

The involvement of the central nervous system (CNS) by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS) is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR) present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resourses available for treating NS. The outcome is variable and is better in cerebral disease.

Analysis of the beta-oxidation of trans-unsaturated fatty acid in recombinant Saccharomyces cerevisiae expressing a peroxisomal PHA synthase reveals the involvement of a reductase-dependent pathway.

The degradation of fatty acids having cis- or trans-unsaturated bond at an even carbon was analyzed in Saccharomyces cerevisiae by monitoring polyhydroxyalkanoate production in the peroxisome. Polyhydroxyalkanaote is synthesized by the polymerization of the beta-oxidation intermediates 3-hydroxy-acyl-CoAs via a bacterial polyhydroxyalkanoate synthase targeted to the peroxisome. The synthesis of polyhydroxyalkanoate in cells grown in media containing 10-cis-heptadecenoic acid was dependent on the presence of 2,4-dienoyl-CoA reductase activity as well as on Delta3,Delta2-enoyl-CoA isomerase activity. The synthesis of polyhydroxyalkanoate from 10-trans-heptadecenoic acid in mutants devoid of 2,4-dienoyl-CoA reductase revealed degradation of the trans fatty acid directly via the enoyl-CoA hydratase II activity of the multifunctional enzyme (MFE), although the level of polyhydroxyalkanoate was 10-25% to that of wild type cells. Polyhydroxyalkanoate produced from 10-trans-heptadecenoic acid in wild type cells showed substantial carbon flux through both a reductase-dependent and a direct MFE-dependent pathway. Flux through beta-oxidation was more severely reduced in mutants devoid of Delta3,Delta2-enoyl-CoA isomerase compared to mutants devoid of 2,4-dienoyl-CoA reductase. It is concluded that the intermediate 2-trans,4-trans-dienoyl-CoA is metabolized in vivo in yeast by both the enoyl-CoA hydratase II activity of the multifunctional protein and the 2,4-dienoyl-CoA reductase, and that the synthesis of the intermediate 3-trans-enoyl-CoA in the absence of the Delta3,Delta2-enoyl-CoA isomerase leads to the blockage of the direct MFE-dependent pathway in vivo.

Personal and Public Involvement Briefing Note

INVOLVE - Briefing note for researchers

Consultation on Personal and Public Involvement strategy

Personal and Public Involvement (PPI) is an integral element of effective commissioning and is underpinned by a core set of values and principles - involving and listening to people in order to help us make services better.It brings about a number of recognised benefits if fully embraced into our culture and practice, these include:Use of service user knowledge and expertise;Better priority setting and decision making;More responsive, appropriate, efficient and tailored services;Transformation and reduction of complaints;Increased levels of service satisfaction;Increased dignity and self worth.The Public Health Agency (PHA) and Health and Social Care Board (HSCB) have now developed a joint Personal and Public Involvement (PPI) Strategy after extensive engagement and discussion. The Strategy has been approved by both organisations and is now being formally consulted on during the period 23rd June 2011 to 15th September 2011.The Strategy is now available for your consideration. We have developed the following documents (please see attachments below):Valuing People, Valuing Their Participation. Involving You and Listening to You Consultation Document.Valuing People, Valuing Their Participation, Involving You and Listening to You. [An Easy Read version of the Personal and Public Involvement Strategy].Valuing People, Valuing Their Participation. [An Equality and Human Rights Screening of the Strategy].Key Questions to guide consideration of the Personal and Public Involvement Strategy.People are encouraged to read the Strategy and to let us have your views.� There is a set of Key Questions, but any comments, ideas and or suggestions that you may have, that could support us in our efforts to embed Personal and Public Involvement into our culture and practice, would be most welcome.Responses should be returned by 4.00pm on Thursday 15th September 2011 to:By post:Martin QuinnRegional PPI LeadPublic Health AgencyGransha Park House15 Gransha ParkLondonderryBT47 6FNBy email: siobhan.carlin@hscni.net By telephone: (028) 7186 0086A more detailed version of the consultation document is avalable by clicking here or contacting Siobhan Carlin, email: siobhan.carlin@hscni.net, Tel: (028) 7186 0086.If you require any of these documents in an alternative format such as Braille, larger print or in another language if you are not fluent in English, please do not hesitate to contact us.A report of feedback received as part of this consultation can be made available upon request.Please be aware that the PHA and HSCB are also currently consulting on the Community Development Strategy.You are invited to consider responding to this consultation as well if appropriate.

HSC R&D Personal and Public Involvement Flyer

Personal and Public Involvement Flyer - How you can get involved.

Regional Health and Social Care Personal and Public Involvement Forum: Annual update report

This is the first annual report of the Regional Health and Social Care Personal and Public Involvement (PPI) Forum. It gives a brief introduction into the concept of PPI, which seeks to involve service users and the public in the planning, delivery and commissioning of services across healthcare in Northern Ireland. The report also provides a background to the development of PPI in Northern Ireland and details on the establishment of the forum.The bulk of the report centres on how PPI is being implemented across all the partner organisations within the healthcare system. Each organisation is introduced and each provides a summary of PPI work it has delivered and planned for the near future. A list of relevant contacts is also included.