Spinal cord vascular degeneration impairs duloxetine penetration

Introduction: Chronic pain is a prevalent physically debilitating health-related morbidity. Frontline analgesics are inadequate, providing only partial pain relief in only a proportion of the patient cohort. Here, we explore whether alterations in spinal cord vascular perfusion are a factor in reducing the analgesic capability of the noradrenaline reuptake inhibitor, duloxetine. Method: An established rodent model of spinal cord vascular degeneration was used. Endothelial-specific vascular endothelial growth factor receptor 2 knockout mouse was induced via hydroxytamoxifen administered via intrathecal injection. Duloxetine was administered via intraperitoneal injection, and nociceptive behavioural testing was performed in both WT and VEGFR2KO mice. LC-MS/MS was performed to explore the accumulation of duloxetine in the spinal cord in WT and VEGFR2KO mice. Results: Spinal cord vascular degeneration leads to heat hypersensitivity and a decline in capillary perfusion. The integrity of noradrenergic projections (dopa - hydroxylase labelled) in the dorsal horn remained unaltered in WT and VEGFR2KO mice. There was an association between dorsal horn blood flow with the abundance of accumulated duloxetine in the spinal cord and analgesic capacity. In VEGFR2KO mice, the abundance of duloxetine in the lumbar spinal cord was reduced and was correlated with reduced anti-nociceptive capability of duloxetine. Discussion: Here, we show that an impaired vascular network in the spinal cord impairs the anti-nociceptive action of duloxetine. This highlights that the spinal cord vascular network is crucial to maintaining the efficacy of analgesics to provide pain relief

Spinal cord vascular degeneration impairs duloxetine penetration

IntroductionChronic pain is a prevalent physically debilitating health-related morbidity. Frontline analgesics are inadequate, providing only partial pain relief in only a proportion of the patient cohort. Here, we explore whether alterations in spinal cord vascular perfusion are a factor in reducing the analgesic capability of the noradrenaline reuptake inhibitor, duloxetine.MethodAn established rodent model of spinal cord vascular degeneration was used. Endothelial-specific vascular endothelial growth factor receptor 2 knockout mouse was induced via hydroxytamoxifen administered via intrathecal injection. Duloxetine was administered via intraperitoneal injection, and nociceptive behavioural testing was performed in both WT and VEGFR2KO mice. LC-MS/MS was performed to explore the accumulation of duloxetine in the spinal cord in WT and VEGFR2KO mice.ResultsSpinal cord vascular degeneration leads to heat hypersensitivity and a decline in capillary perfusion. The integrity of noradrenergic projections (dopa - hydroxylase labelled) in the dorsal horn remained unaltered in WT and VEGFR2KO mice. There was an association between dorsal horn blood flow with the abundance of accumulated duloxetine in the spinal cord and analgesic capacity. In VEGFR2KO mice, the abundance of duloxetine in the lumbar spinal cord was reduced and was correlated with reduced anti-nociceptive capability of duloxetine.DiscussionHere, we show that an impaired vascular network in the spinal cord impairs the anti-nociceptive action of duloxetine. This highlights that the spinal cord vascular network is crucial to maintaining the efficacy of analgesics to provide pain relief

Nonlinear Gravitational Waves: Their Form and Effects

A gravitational wave must be nonlinear to be able to transport its own source, that is, energy and momentum. A physical gravitational wave, therefore, cannot be represented by a solution to a linear wave equation. Relying on this property, the second-order solution describing such physical waves is obtained. The effects they produce on free particles are found to consist of nonlinear oscillations along the direction of propagation.Comment: 15 pages, no figures. v2: presentation changes aiming at clarifying the text; matches published versio

Risky use of alcohol, drugs and cigarettes in a psychosis unit: a 1 1/2 year follow-up of stability and changes after initial screening

<p>Abstract</p> <p>Background</p> <p>Co-morbidity with substance use disorders negatively influences overall functioning in patients with psychosis. However, frequencies and courses of risky use of alcohol, drugs and cigarettes are rarely investigated in patients at psychosis units.</p> <p>The purpose of this study is to describe the use of alcohol, drugs and cigarettes in patients at a psychosis unit over a 1 1/2 year period after them having taken part in a screening investigation including a feed-back of the results to personnel. Relationships with sex and age are also described.</p> <p>Methods</p> <p>The patients' use of the substances was examined at baseline and at follow-up using three self-reporting instruments: Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT) and Fagerstrom Test for Nicotine Dependence (FTND).</p> <p>Results</p> <p>One hundred and eighty-six patients out of 238 at baseline (78 percent) took part in the follow-up. Total AUDIT score decreased in women. Older men more often developed a risky alcohol use. Older women tended to reduce their risky drug habits. On a group level the habits mostly were stable, but 11 percent changed their alcohol habits and 15 percent changed their smoking habits from risky to no/low risky use, or vice versa. Nine percent changed their drug habits, predominantly from risky to no/low risky use.</p> <p>Conclusion</p> <p>A more active approach towards alcohol, drug and smoking habits in psychosis units would probably be beneficial.</p

Alelopatia do óleo essencial de alfavaca em sementes de capim-braquiária

O manejo de plantas daninhas no meio agrícola gera prejuízos ao meio ambiente e gastos excessivos com o uso de herbicidas. Nesta situação há constante busca por meios alternativos de controle. Diante do exposto, objetivou-se com o presente trabalho avaliar o efeito alelopático do óleo essencial da alfavaca (Ocimum gratissimum) sobre a germinação e desenvolvimento de plântulas do capim braquiária (Urochloa brizantha ‘Piatã’). Foram utilizadas sementes viáveis de capim braquiária e óleo essencial (OE) de alfavaca nas concentrações 0; 0,05; 0,10; 0,15; 0,20 e 0,25%. Nos bioensaios utilizou-se caixas do tipo gerbox com 50 sementes de U. brizantha com quatro repetições, num delineamento inteiramente casualizado. Foi avaliado a germinação, comprimento de raiz, comprimento de parte aérea, biomassa fresca e seca das plântulas e número de plântulas normais e anormais. O OE da alfavaca apresentou uma redução significativa na germinação a partir de 0,05%, enquanto que houve inibição completa a 0,15%. O crescimento e o acúmulo de biomassa das plântulas foram reduzidos em resposta às concentrações de óleo. A concentração de 0,15% de OE da alfavaca foi eficiente em reduzir a germinação e o desenvolvimento do capim braquiária. O óleo essencial da alfavaca apresenta um potencial uso como bioherbida e pode constituir um manejo alternativo no controle de plantas daninhas

Searches for Gravitational Waves from Binary Neutron Stars: A Review

A new generation of observatories is looking for gravitational waves. These waves, emitted by highly relativistic systems, will open a new window for ob- servation of the cosmos when they are detected. Among the most promising sources of gravitational waves for these observatories are compact binaries in the final min- utes before coalescence. In this article, we review in brief interferometric searches for gravitational waves emitted by neutron star binaries, including the theory, instru- mentation and methods. No detections have been made to date. However, the best direct observational limits on coalescence rates have been set, and instrumentation and analysis methods continue to be refined toward the ultimate goal of defining the new field of gravitational wave astronomy.Comment: 30 pages, 5 Figures, to appear in "Short-Period Binary Stars: Observations, Analyses, and Results", Ed.s Eugene F. Milone, Denis A. Leahy, David W. Hobil

Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy

Background: Cocaine exposure during pregnancy has been reported to have detrimental effects on the fetus. Objective: To describe the findings on cranial ultrasonography (CUS) as part of a neonatal screening programme for exposed neonates. Materials and methods: The study was a semiprospective analysis of a 12-year cohort of neonates born to mothers who had used cocaine during their pregnancy and who had follow-up according to a strict clinical protocol. Results: In total, 154 neonates (78 boys, 76 girls) were included, of whom 29 (19%) were born preterm, and 125 (81%) were born full-term. Abnormalities on CUS were seen in 37 neonates (24%; 95% CI 18-31%). The abnormalities were classified as minor in 20 (13%; 95% CI 9-19%) and mildly abnormal in 17 (11%; 95% CI 7-17%). None of the infants showed severe abnormalities. The abnormalities were not associated with the duration or maximum amount of cocaine use during pregnancy. Conclusion: None of the infants had severe abnormalities. Detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, we feel that routine cranial ultrasonography in this population is not warranted

The Morningside Initiative: Collaborative Development of a Knowledge Repository to Accelerate Adoption of Clinical Decision Support

The Morningside Initiative is a public-private activity that has evolved from an August, 2007, meeting at the Morningside Inn, in Frederick, MD, sponsored by the Telemedicine and Advanced Technology Research Center (TATRC) of the US Army Medical Research Materiel Command. Participants were subject matter experts in clinical decision support (CDS) and included representatives from the Department of Defense, Veterans Health Administration, Kaiser Permanente, Partners Healthcare System, Henry Ford Health System, Arizona State University, and the American Medical Informatics Association (AMIA). The Morningside Initiative was convened in response to the AMIA Roadmap for National Action on Clinical Decision Support and on the basis of other considerations and experiences of the participants. Its formation was the unanimous recommendation of participants at the 2007 meeting which called for creating a shared repository of executable knowledge for diverse health care organizations and practices, as well as health care system vendors. The rationale is based on the recognition that sharing of clinical knowledge needed for CDS across organizations is currently virtually non-existent, and that, given the considerable investment needed for creating, maintaining and updating authoritative knowledge, which only larger organizations have been able to undertake, this is an impediment to widespread adoption and use of CDS. The Morningside Initiative intends to develop and refine (1) an organizational framework, (2) a technical approach, and (3) CDS content acquisition and management processes for sharing CDS knowledge content, tools, and experience that will scale with growing numbers of participants and can be expanded in scope of content and capabilities. Intermountain Healthcare joined the initial set of participants shortly after its formation. The efforts of the Morningside Initiative are intended to serve as the basis for a series of next steps in a national agenda for CDS. It is based on the belief that sharing of knowledge can be highly effective as is the case in other competitive domains such as genomics. Participants in the Morningside Initiative believe that a coordinated effort between the private and public sectors is needed to accomplish this goal and that a small number of highly visible and respected health care organizations in the public and private sector can lead by example. Ultimately, a future collaborative knowledge sharing organization must have a sustainable long-term business model for financial support

A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus isolates from smallholder duck farms in Central Java, Indonesia during 2007-2008

Background: Indonesia is one of the countries most severely affected by H5N1 highly pathogenic avian influenza (HPAI) virus in terms of poultry and human health. However, there is little information on the diversity of H5N1 viruses circulating in backyard farms, where chickens and ducks often intermingle. In this study, H5N1 virus infection occurring in 96 smallholder duck farms in central Java, Indonesia from 2007-2008 was investigated and the molecular and antigenic characteristics of H5N1 viruses isolated from these farms were analysed