The global role of kidney transplantation

World Kidney Day on March 8 th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit

A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis

The effects of an analgesic treatment (lidocaine patches) on brain activity in chronic low back pain (CBP) and in knee osteoarthritis (OA) were investigated using serial fMRI (contrasting fMRI between before and after two weeks of treatment). Prior to treatment brain activity was distinct between the two groups: CBP spontaneous pain was associated mainly with activity in medial prefrontal cortex, while OA painful mechanical knee stimulation was associated with bilateral activity in the thalamus, secondary somatosensory, insular, and cingulate cortices, and unilateral activity in the putamen and amygdala. After 5% lidocaine patches were applied to the painful body part for two weeks, CBP patients exhibited a significant decrease in clinical pain measures, while in OA clinical questionnaire based outcomes showed no treatment effect but stimulus evoked pain showed a borderline decrease. The lidocaine treatment resulted in significantly decreased brain activity in both patient groups with distinct brain regions responding in each group, and sub-regions within these areas were correlated with pain ratings specifically for each group (medial prefrontal cortex in CBP and thalamus in OA). We conclude that the two chronic pain conditions involve distinct brain regions, with OA pain engaging many brain regions commonly observed in acute pain. Moreover, lidocaine patch treatment modulates distinct brain circuitry in each condition, yet in OA we observe divergent results with fMRI and with questionnaire based instruments

Transition from pediatric to adult renal services: a consensus statement by the International Society of Nephrology (ISN) and the International Pediatric Nephrology Association (IPNA)

The transfer of young patients from pediatric to adult renal care takes place after a transition process which involves both sides. It is important that it is individualized for each young person, focusing on self-management skills as well as assessing support structures. The consensus statement has been developed by the panel of adult and pediatric nephrologists and endorsed by the councils of both ISN and IPNA. It is hoped that the statement will provide a basis for the development of locally appropriate recommendations for clinical practice

Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain,”The

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n ϭ 13 and n ϭ 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n ϭ 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self

South African Children: A Matched Cohort Study of Neurodevelopmental Impairment in Survivors of Invasive Group B Streptococcus Disease Aged 5 to 8 Years.

BACKGROUND: Invasive group B Streptococcus (iGBS) sepsis and meningitis are important causes of child mortality, but studies on neurodevelopmental impairment (NDI) after iGBS are limited. Using Griffiths Mental Development Scales-Extended Revised (GMDS-ER), we described NDI in iGBS survivors and non-iGBS children from South Africa, as part of a 5-country study. METHODS: We identified children aged 5-8 years with a history of iGBS and children with no history of iGBS between October 2019 and January 2021. Children were matched on sex, and birth data (month, year) (matched cohort study). Moderate or Severe NDI was the primary outcome as a composite of GMDS-ER motor, GMDS-ER cognition, hearing, and vision. Secondary outcomes included mild NDI, any emotional-behavioral problems, and GMDS-ER developmental quotients (DQ) calculated by dividing the age equivalent GMDS-ER score by the chronological age. RESULTS: In total, 160 children (iGBS survivors, 43; non-iGBS, 117) were assessed. Among iGBS survivors 13 (30.2%) had meningitis, and 30 (69.8%) had sepsis. Six (13.9%) iGBS survivors, and 5 (4.3%) non-iGBS children had moderate or severe NDI. Children who survived iGBS were 5.56 (95% confidence interval [CI]: 1.07-28.93; P = .041) times more likely to have moderate or severe NDI at 5-8 years than non-iGBS children. Compared to the non-iGBS children, iGBS meningitis survivors had a significantly lower global median DQ (P < .05), as well as a lower median DQ for the language GMDS-ER subscale and performance GMDS-ER subscale (P < .05). CONCLUSIONS: Children surviving iGBS, particularly meningitis, are more likely to have NDI at 5-8 years compared to non-iGBS children. Further research is required to improve detection and care for at-risk newborns

Transboundary water interaction III: contest and compliance

This paper serves international water conflict resolution efforts by examining the ways that states contest hegemonic transboundary water arrangements. The conceptual framework of dynamic transboundary water interaction that it presents integrates theories about change and counter-hegemony to ascertain coercive, leverage, and liberating mechanisms through which contest and transformation of an arrangement occur. While the mechanisms can be active through sociopolitical processes either of compliance or of contest of the arrangement, most transboundary water interaction is found to contain elements of both. The role of power asymmetry is interpreted through classification of intervention strategies that seek to either influence or challenge the arrangements. Coexisting contest and compliance serve to explain in part the stasis on the Jordan and Ganges rivers (where the non-hegemons have in effect consented to the arrangement), as well as the changes on the Tigris and Mekong rivers, and even more rapid changes on the Amu Darya and Nile rivers (where the non-hegemons have confronted power asymmetry through influence and challenge). The framework also stresses how transboundary water events that may appear isolated are more accurately read within the many sociopolitical processes and arrangements they are shaped by. By clarifying the typically murky dynamics of interstate relations over transboundary waters, furthermore, the framework exposes a new suite of entry points for hydro-diplomatic initiatives

Dietary advice for muscularity, leanness and weight control in Men's Health magazine: a content analysis

Background: The dietary content of advice in men’s lifestyle magazines has not been closely scrutinised. Methods: We carried out an analysis of such content in all 2009 issues (n = 11) of Men’s Health (MH) focusing on muscularity, leanness and weight control. Results: Promotion of a mesomorphic body image underpinned advice to affect muscle building and control weight. Diet advice was underpinned by a strong pseudo-scientific discourse, with citation of expert sources widely used to legitimise the information. Frequently multiple dietary components were advocated within one article e.g. fat, omega-3 fatty acids, thiamine, zinc and high-glycaemic index foods. Furthermore advice would cover numerous nutritional effects, e.g. strengthening bones, reducing stress and boosting testosterone, with little contextualisation. The emphasis on attainment of a mesomorphic body image permitted promotion of slimming diets. Advice to increase calorie and protein intake to augment muscle mass was frequent (183 and 262 references, respectively). Such an anabolic diet was advised in various ways, including consumption of traditional protein foods (217 references) and sports foods (107 references), thereby replicating muscle magazines’ support for nutritional supplements. Although advice to increase consumption of red meat was common (52 references), fish and non-flesh sources of protein (eggs, nuts & pulses, and soy products) together exceeded red meat in number of recommendations (206 references). Advice widely asserted micronutrients and phytochemicals from plant food (161 references) as being important in muscle building. This emphasis diverges from stereotypical gender-based food consumption patterns. Dietary advice for control of body weight largely replicated that of muscularity, with strong endorsement to consume fruits and vegetables (59 references), diets rich in nuts and pulses and fish (66 references), as well as specific micronutrients and phytochemicals (62 references). Notably there was emphasis on fat-burning, good fats and consumption of single foods, with relatively little mention of dietary restriction. Conclusions: Despite the widespread use of scientific information to endorse dietary advice, the content, format and scientific basis of dietary content of MH leaves much to be desired. The dietary advice as provided may not be conducive to public health

Overview of the Alliance for Cellular Signaling

The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells-B lymphocytes (the cells of the immune system) and cardiac myocytes-to facilitate quantitative modelling. One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62977/1/nature01304.pd

Directed Evolution Generates a Novel Oncolytic Virus for the Treatment of Colon Cancer

Background Viral-mediated oncolysis is a novel cancer therapeutic approach with the potential to be more effective and less toxic than current therapies due to the agents selective growth and amplification in tumor cells. To date, these agents have been highly safe in patients but have generally fallen short of their expected therapeutic value as monotherapies. Consequently, new approaches to generating highly potent oncolytic viruses are needed. To address this need, we developed a new method that we term “Directed Evolution” for creating highly potent oncolytic viruses. Methodology/Principal Findings Taking the “Directed Evolution” approach, viral diversity was increased by pooling an array of serotypes, then passaging the pools under conditions that invite recombination between serotypes. These highly diverse viral pools were then placed under stringent directed selection to generate and identify highly potent agents. ColoAd1, a complex Ad3/Ad11p chimeric virus, was the initial oncolytic virus derived by this novel methodology. ColoAd1, the first described non-Ad5-based oncolytic Ad, is 2–3 logs more potent and selective than the parent serotypes or the most clinically advanced oncolytic Ad, ONYX-015, in vitro. ColoAd1's efficacy was further tested in vivo in a colon cancer liver metastasis xenograft model following intravenous injection and its ex vivo selectivity was demonstrated on surgically-derived human colorectal tumor tissues. Lastly, we demonstrated the ability to arm ColoAd1 with an exogenous gene establishing the potential to impact the treatment of cancer on multiple levels from a single agent. Conclusions/Significance Using the “Directed Evolution” methodology, we have generated ColoAd1, a novel chimeric oncolytic virus. In vitro, this virus demonstrated a &gt;2 log increase in both potency and selectivity when compared to ONYX-015 on colon cancer cells. These results were further supported by in vivo and ex vivo studies. Furthermore, these results have validated this methodology as a new general approach for deriving clinically-relevant, highly potent anti-cancer virotherapies