Protective vascular coagulation in response to bacterial infection of the kidney is regulated by bacterial lipid A and host CD147

Bacterial infection of the kidney leads to a rapid cascade of host protective responses, many of which are still poorly understood. We have previously shown that following kidney infection with uropathogenicEscherichia coli (UPEC), vascular coagulation is quickly initiated in local perivascular capillaries that protects the host from progressing from a local infection to systemic sepsis. The signaling mechanisms behind this response have not however been described. In this study, we use a number ofin vitro andin vivo techniques, including intravital microscopy, to identify two previously unrecognized components influencing this protective coagulation response. The acylation state of the Lipid A of UPEC lipopolysaccharide (LPS) is shown to alter the kinetics of local coagulation onsetin vivo. We also identify epithelial CD147 as a potential host factor influencing infection-mediated coagulation. CD147 is expressed by renal proximal epithelial cells infected with UPEC, contingent to bacterial expression of the α-hemolysin toxin. The epithelial CD147 subsequently can activate tissue factor on endothelial cells, a primary step in the coagulation cascade. This study emphasizes the rapid, multifaceted response of the kidney tissue to bacterial infection and the interplay between host and pathogen during the early hours of renal infection

On the Role of the Accretion Disk in Black Hole Disk-Jet Connections

Models of jet production in black hole systems suggest that the properties of the accretion disk - such as its mass accretion rate, inner radius, and emergent magnetic field - should drive and modulate the production of relativistic jets. Stellar-mass black holes in the "low/hard" state are an excellent laboratory in which to study disk-jet connections, but few coordinated observations are made using spectrometers that can incisively probe the inner disk. We report on a series of 20 Suzaku observations of Cygnus X-1 made in the jet-producing low/hard state. Contemporaneous radio monitoring was done using the Arcminute MicroKelvin Array radio telescope. Two important and simple results are obtained: (1) the jet (as traced by radio flux) does not appear to be modulated by changes in the inner radius of the accretion disk; and (2) the jet is sensitive to disk properties, including its flux, temperature, and ionization. Some more complex results may reveal aspects of a coupled disk-corona-jet system. A positive correlation between the reflected X-ray flux and radio flux may represent specific support for a plasma ejection model of the corona, wherein the base of a jet produces hard X-ray emission. Within the framework of the plasma ejection model, the spectra suggest a jet base with v/c ~ 0.3, or the escape velocity for a vertical height of z ~ 20 GM/c^2 above the black hole. The detailed results of X-ray disk continuum and reflection modeling also suggest a height of z ~ 20 GM/c^2 for hard X-ray production above a black hole, with a spin in the range 0.6 < a < 0.99. This height agrees with X-ray time lags recently found in Cygnus X-1. The overall picture that emerges from this study is broadly consistent with some jet-focused models for black hole spectral energy distributions in which a relativistic plasma is accelerated at z = 10-100 GM/c^2.Comment: Accepted for publication in Ap

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Large infrapatellar ganglionic cyst of the knee fat pad: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Large ganglionic cystic formations arising from the infrapatellar fat pad are quite uncommon and only a few are mentioned in the literature. An open excision in these cases is mandatory.</p> <p>Case presentation</p> <p>We report the case of a large infrapatellar fat pad ganglion in a 37-year-old Greek man with chronic knee discomfort. The ganglionic cyst originated from the infrapatellar fat pad and had no intrasynovial extension. The final diagnosis was determined with magnetic resonance imaging of the knee, and the lesion was treated with surgery.</p> <p>Conclusions</p> <p>These lesions are asymptomatic in most cases but often are misdiagnosed as meniscal or ligamentous lesions of the knee joint. Nowadays, the therapeutic trend for such lesions is arthroscopic excision, but when there is a large ganglion, as in this case report, the treatment should be an open and thorough resection. This report is intended mostly but not exclusively for clinical physicians and radiologists.</p

“We need a one-stop-shop” : co-creating the model of care for a multidisciplinary memory clinic with community members, GPs, aged care workers, service providers, and policy-makers

Background: Timely diagnosis of dementia has a wide range of benefits including reduced hospital emergency department presentations, admissions and inpatient length of stay, and improved quality of life for patients and their carers by facilitating access to treatments that reduce symptoms, and allow time to plan for the future. Memory clinics can provide such services, however there is no 'gold standard' model of care. This study involved the co-creation of a model of care for a new multidisciplinary memory clinic with local community members, General Practitioners (GPs), policy-makers, community aged care workers, and service providers. Methods: Data collection comprised semi-structured interviews (N=98) with 20 GPs, and three 2-h community forums involving 53 seniors and community/local government representatives, and 25 community healthcare workers. Interviews and community forums were audio-recorded, transcribed verbatim, and coded by thematic analysis using Quirkos. Results: GPs’ attitudes towards their role in assessing people with dementia varied. Many GPs reported that they found it useful for patients to have a diagnosis of dementia, but required support from secondary care to make the diagnosis and assist with subsequent management. Community forum participants felt they had a good knowledge of available dementia resources and services, but noted that these were highly fragmented and needed to be easier to navigate for the patient/carer via a 'one-stop-shop' and the provision of a dementia key worker. Expectations for the services and features of a new memory clinic included diagnostic services, rapid referrals, case management, education, legal services, culturally sensitive and appropriate services, allied health, research participation opportunities, and clear communication with GPs. Participants described several barriers to memory clinic utilisation including transportation access, funding, awareness, and costs. Conclusion: This study demonstrates the importance of working with stakeholders to co-design models of care for people with dementia that take into account the local communities’ needs. Findings pave the way for the development of a potential new “gold standard” memory clinic model of care and operationalise new national clinical guidelines

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Loss of One Engrailed1 Allele Enhances Induced α-Synucleinopathy

Parkinson’s disease (PD) is a synucleinopathy that has multiple neuropathological characteristics, with nigrostriatal dopamine system degeneration being a core feature. Current models of PD pathology typically fail to recapitulate several attributes of the pathogenic process and neuropathology. We aimed to define the effects of combining a mouse model exhibiting multiple PD-like changes with intrastriatal injections of α-synuclein (α-syn) pre-formed fibril (PFFs) aggregates. We employed the heterozygous Engrailed 1 (En1+/–) mouse that features several pathophysiological hallmarks of clinical PD.La enfermedad de Parkinson (EP) es una sinucleinopatía que tiene múltiples características neuropatológicas, siendo la degeneración del sistema dopaminérgico nigroestriatal una característica central. Los modelos actuales de patología de la EP generalmente no logran recapitular varios atributos del proceso patogénico y la neuropatología. Nuestro objetivo fue definir los efectos de combinar un modelo de ratón que presentaba múltiples cambios similares a los de la EP con inyecciones intraestriatales de agregados de fibrillas preformadas (PFF) de α-sinucleína (α-syn). Empleamos el ratón heterocigoto Engrailed 1 (En1+/–) que presenta varias características fisiopatológicas de la EP clínica