A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice

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Amyloid angiopathy of the floor of the mouth: a case report and review of the literature

Amyloidosis is a rare disease characterised by the deposition of insoluble extracellular fibrillar proteins in various tissues of the body. The pattern of manifestation is organ dependent and also on whether the disease is localised or systemic, primary or secondary

Enhanced Leishmania braziliensis Infection Following Pre-Exposure to Sandfly Saliva

Parasites of the genus Leishmania cause a variety of diseases known as leishmaniasis, that are transmitted by bites of female sand flies that, during blood-feeding, inject humans with parasites and saliva. It was shown that, in mice, immunity to sand-fly saliva is able to protect against the development of leishmaniasis. We have investigated, in the present study, whether this finding extends the sand fly species Lutzomyia intermedia, which is responsible for transmission of Leishmania braziliensis, a parasite species able to cause destructive skin lesions that can be fatal if left untreated. We observed that mice injected with sand fly saliva develop a specific immune response against salivary proteins. Most importantly, however, this immune response was unable to protect mice against a challenge infection with L. braziliensis, indicating that exposure to this sand fly saliva is harmful to the host. Indeed, subjects with cutaneous leishmaniasis have a higher immune response against L. intermedia saliva. These findings indicate that the anti-saliva immune response to sand fly saliva plays an important role in the outcome of leishmaniasis caused by L. braziliensis, in both mice and humans, and emphasize possible hurdles in the development of vaccines based on sand fly saliva

Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation

Introduction: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. Methods: Two specific n-3 compounds were tested, namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), each at 0.1, 1 and 10 μM. Full thickness bovine cartilage explants, 5 mm in diameter, were cultured for 5 days with or without IL-1β and in the presence or absence of each n-3 compound. The media were replaced every 24 hours and assayed for sGAG content using the 1,9-dimethylmethylene blue (DMB) method. Chondrocyte viability was determined at the end of the culture period using fluorescence microscopy to visualise cells labelled with calcein AM and ethidium homodimer. Results: Treatment with IL-1β (10 ng.ml-1) produced a large increase in sGAG release compared to untreated controls, but with no effect on cell viability, which was maintained above 80% for all treatments. In the absence of IL-1β, both n-3 compounds induced a mild catabolic response with increased loss of sGAG, particularly at 10 μM. By contrast, in the presence of IL-1β, both EPA and DHA at 0.1 and 1 μM significantly reduced IL-1β-mediated sGAG loss. The efficacy of the EPA treatment was maintained at approximately 75% throughout the 5-day period. However, at the same concentrations, the efficacy of DHA, although initially greater, reduced to approximately half that of EPA after 5 days. For both EPA and DHA, the highest dose of 10 μM was less effective. Conclusions: The results support the hypothesis that n-3 compounds are anti-inflammatory through competitive inhibition of the arachidonic acid oxidation pathway. The efficacy of these compounds is likely to be even greater at more physiological levels of IL-1β. Thus we suggest that n-3 PUFAs, particularly EPA, have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory joint disease

Marsh macrophyte responses to inundation anticipate impacts of sea-level rise and indicate ongoing drowning of North Carolina marshes

In situ persistence of coastal marsh habitat as sea level rises depends on whether macrophytes induce compensatory accretion of the marsh surface. Experimental planters in two North Carolina marshes served to expose two dominant macrophyte species to six different elevations spanning 0.75 m (inundation durations 0.4–99 %). Spartina alterniflora and Juncus roemerianus exhibited similar responses—with production in planters suggesting initial increases and then demonstrating subsequent steep declines with increasing inundation, conforming to a segment of the ecophysiological parabola. Projecting inundation levels experienced by macrophytes in the planters onto adjacent marsh platforms revealed that neither species occupied elevations associated with increasing production. Declining macrophyte production with rising seas reduces both bioaccumulation of roots below-ground and baffle-induced sedimentation above-ground. By occupying only descending portions of the parabola, macrophytes in central North Carolina marshes are responding to rising water levels by progressive declines in production, ultimately leading to marsh drowning

Discovery of Markers of Exposure Specific to Bites of Lutzomyia longipalpis, the Vector of Leishmania infantum chagasi in Latin America

Leishmania parasites are transmitted by the bite of an infected vector sand fly that injects salivary molecules into the host skin during feeding. Certain salivary molecules can produce antibodies and can be used as an indicator of exposure to a vector sand fly and potentially the disease it transmits. Here we identified potential markers of specific exposure to the sand fly Lutzomyia longipalpis, the vector of visceral leishmaniasis in Latin America. Initially, we determined which of the salivary proteins produce antibodies in humans, dogs, and foxes from areas endemic for the disease. To identify potential specific markers of vector exposure, we produced nine different recombinant salivary proteins from Lu. longipalpis and tested for their recognition by individuals exposed to another human-biting sand fly, Lu. intermedia, that transmits cutaneous leishmaniasis and commonly occurs in the same endemic areas as Lu. longipalpis. Two of the nine salivary proteins were recognized only by humans exposed to Lu. longipalpis, suggesting they are immunogenic proteins and may be useful in epidemiological studies. The identification of specific salivary proteins as potential markers of exposure to vector sand flies will increase our understanding of vector–human interaction, bring new insights to vector control, and in some instances act as an indicator for risk of acquiring disease

Androgen Regulation of 5α-Reductase Isoenzymes in Prostate Cancer: Implications for Prostate Cancer Prevention

The enzyme 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), performs key functions in the androgen receptor (AR) signaling pathway. The three isoenzymes of 5α-reductase identified to date are encoded by different genes: SRD5A1, SRD5A2, and SRD5A3. In this study, we investigated mechanisms underlying androgen regulation of 5α-reductase isoenzyme expression in human prostate cells. We found that androgen regulates the mRNA level of 5α-reductase isoenzymes in a cell type–specific manner, that such regulation occurs at the transcriptional level, and that AR is necessary for this regulation. In addition, our results suggest that AR is recruited to a negative androgen response element (nARE) on the promoter of SRD5A3 in vivo and directly binds to the nARE in vitro. The different expression levels of 5α-reductase isoenzymes may confer response or resistance to 5α-reductase inhibitors and thus may have importance in prostate cancer prevention

Are pediatric Open Access journals promoting good publication practice? An analysis of author instructions

<p>Abstract</p> <p>Background</p> <p>Several studies analyzed whether conventional journals in general medicine or specialties such as pediatrics endorse recommendations aiming to improve publication practice. Despite evidence showing benefits of these recommendations, the proportion of endorsing journals has been moderate to low and varied considerably for different recommendations. About half of pediatric journals indexed in the Journal Citation Report referred to the Uniform Requirements for Manuscripts of the International Committee of Medical Journal Editors (ICMJE) but only about a quarter recommended registration of trials. We aimed to investigate to what extent pediatric open-access (OA) journals endorse these recommendations. We hypothesized that a high proportion of these journals have adopted recommendations on good publication practice since OA electronic publishing has been associated with a number of editorial innovations aiming at improved access and transparency.</p> <p>Methods</p> <p>We identified 41 journals publishing original research in the subject category "Health Sciences, Medicine (General), Pediatrics" of the Directory of Open Access Journals <url>http://www.doaj.org</url>. From the journals' online author instructions we extracted information regarding endorsement of four domains of editorial policy: the Uniform Requirements for Manuscripts, trial registration, disclosure of conflicts of interest and five major reporting guidelines such as the CONSORT (Consolidated Standards of Reporting Trials) statement. Two investigators collected data independently.</p> <p>Results</p> <p>The Uniform Requirements were mentioned by 27 (66%) pediatric OA journals. Thirteen (32%) required or recommended trial registration prior to publication of a trial report. Conflict of interest policies were stated by 25 journals (61%). Advice about reporting guidelines was less frequent: CONSORT was referred to by 12 journals (29%) followed by other reporting guidelines (MOOSE, PRISMA or STARD) (8 journals, 20%) and STROBE (3 journals, 7%). The EQUATOR network, a platform of several guideline initiatives, was acknowledged by 4 journals (10%).</p> <p>Journals published by OA publishing houses gave more guidance than journals published by professional societies or other publishers.</p> <p>Conclusions</p> <p>Pediatric OA journals mentioned certain recommendations such as the Uniform Requirements or trial registration more frequently than conventional journals; however, endorsement is still only moderate. Further research should confirm these exploratory findings in other medical fields and should clarify what the motivations and barriers are in implementing such policies.</p