Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

BACKGROUND: Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 μl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. RESULTS: Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16–25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60–31.8]; (P = NS) and 9.8 [1.7–27.3] (controls: 10.5 [2.4–21.75]) in animals treated with high dose RO 25-6981 (P = NS). CONCLUSIONS: Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures

Successful Treatment of PulmonaryInvasive Aspergillosis with Voriconazole in Patients who FailedConventional Therapy

Abstract.: Background: The incidence of fungal infections, including those due to Aspergillosis species has continued to increase in recent years. Invasive aspergillosis remains an important cause of morbidity and mortality, despite therapeutics interventions. Patients and Methods: We reported five cases of invasive pulmonary aspergillosis treated with voriconazole failing to respond to conventional treatments. Results: The clinical and radiological resolution of pulmonary aspergillosis reported in these cases following therapy with voriconazole is remarkable, considering the infections had proved refractory to standard antifungal therapies. Long-term therapy (in two cases ≥ 1 year, in one case 6 months) was very well tolerated by patients who were unable to tolerate other antifungal agents. Conclusion: Therapy with voriconazole offers a new therapeutic option for otherwise difficult-to-treat infections and the potential to significantly improve the management of Aspergillosis infection

A study on cercarial dermatitis in Khuzestan province, south western Iran

BACKGROUND: Cercarial dermatitis' or swimmer's itch' is an itchy inflammatory response to the penetration of the skin by non-human schistosome parasites. In the hot season, (May to September) in Khuzestan province in the south west of Iran, swimming in canals and agriculture activities in swampy areas are common. This survey was made on people from villages north of Ahwaz city in south west Iran, to estimate cercarial dermatitis in this region. METHODS: 2000 people were observed for clinical signs of cercarial dermatitis. Also 2000 Lymnaea gedrosiana snails were collected from agriculture canals and examined for animal schistosome cercariae during 1998–2000. RESULTS: From this survey 1.1% of people had pruritic maculopapular rash on their feet, hands or other parts of body. From the total of examined snails, 2.4% were found to be infected with bird schistosome cercariae including Trichobilharzia species. CONCLUSION: Cercarial dermatitis could be a health problem in this area. This is the first report of cercarial dermatitis from this region of Iran

Producing valid statistics when legislation, culture, and medical practices differ for births at or before the threshold of survival: Report of a European workshop

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Small Nuclear RNAs Encoded by Herpesvirus saimiri Upregulate the Expression of Genes Linked to T Cell Activation in Virally Transformed T Cells

SummarySeven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a γ Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro [1–4]. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro [5]. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor β and γ chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins—SKAP55, granulysin, and NKG7—linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency

The utility of the “Arable Weeds and Management in Europe” database: Challenges and opportunities of combining weed survey data at a European scale

Over the last 30 years many studies have surveyed weed vegetation on arable land. The “Arable Weeds and Management in Europe” (AWME) database is a collection of 36 of these surveys and the associated management data. Here we review the challenges associated with combining disparate datasets and explore some of the opportunities for future research that present themselves thanks to the advent of the AWME database. We present three case studies repeating previously published national scale analyses with data from a larger spatial extent. We demonstrate that i) the standardisation of abundance data to a common measure, prior to the analysis of the combined dataset, has little impact on the outcome of the analyses, ii) the increased length of environmental or management gradients allows for greater confidence in conclusions, iii) the main conclusions of analyses done at different spatial extents remain consistent. These case studies demonstrate the utility of a Europe-wide weed survey database, for clarifying or extending results obtained from studies at smaller scales. This Europe-wide data collection offers many more opportunities for analysis that could not be addressed in smaller datasets; including questions about the effects of climate change, macro-ecological and biogeographical issues related to weed diversity as well as the dominance or rarity of specific weeds in Europe

An investigation into the depth of penetration of low level laser therapy through the equine tendon in vivo

Low level laser therapy (LLLT) is frequently used in the treatment of wounds, soft tissue injury and in pain management. The exact penetration depth of LLLT in human tissue remains unspecified. Similar uncertainty regarding penetration depth arises in treating animals. This study was designed to test the hypothesis that transmission of LLLT in horses is increased by clipping the hair and/or by cleaning the area to be treated with alcohol, but is unaffected by coat colour. A LLLT probe (810 nm, 500 mW) was applied to the medial aspect of the superficial flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied to the lateral aspect, directly opposite the laser probe to measure the amount of light transmitted. Light transmission was not affected by individual horse, coat colour or leg. However, it was associated with leg condition (F = 4.42, p = 0.0032). Tendons clipped dry and clipped and cleaned with alcohol, were both associated with greater transmission of light than the unprepared state. Use of alcohol without clipping was not associated with an increase in light transmission. These results suggest that, when applying laser to a subcutaneous structure in the horse, the area should be clipped and cleaned beforehand

Students for global oncology: Building a movement for student education and engagement in an emerging field

Program/Project Purpose: Increased recognition of the global cancer burden and inequalities in care and outcomes have led to the growing field of global oncology, focused on strengthening health systems to improve cancer prevention and care. Motivated students and trainees are in need of pathways to approach these challenges. In 2012, Harvard Medical students formed Students for Global Oncology (S4GO), an adjunct to the larger inter-professional organization Global Oncology. The group had three aims: 1) connect students with mentors in the field, 2) develop novel approaches in global oncology, and 3) disseminate global oncology knowledge. Structure/Method/Design: S4GO has created content and organized events to increase awareness about the global cancer burden, while promoting trainee opportunities in research and practical hands-on projects. Engagement was enhanced by mentorship from more senior students and faculty, to interface with existing global oncology projects. Outcomes & Evaluation: Since 2012, S4GO has grown from two to 68 students. Currently, new chapters at seven other institutions in the US and Canada are being developed. As of October 2014, S4GO has developed a case-based cancer care delivery curriculum with six case-based seminars, along with numerous blog entries and interviews of leading researchers in the field of global oncology, all available on the S4GO website. Students have completed projects in over nine countries and are actively involved in technological and on-the-ground efforts to develop creative solutions and collaborations aimed at easing the global cancer burden. Held in February 2014, the inaugural student-led global oncology symposium involved 200 individuals from across the world, including leaders in global health, pharmaceutical industry, public policy and cancer care. This symposium has been viewed by hundreds online and has fostered novel collaborations and projects focused on enhancing cancer care delivery. Going Forward: In the coming years, S4GO will continue efforts to build awareness and catalyze creative solutions for cancer care in resource-limited settings. These efforts will increase exposure for novel and successful student efforts as well as intra-institutional and intra-professional activity