Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences

BACKGROUND: Analytical imaging by secondary ion mass spectrometry (SIMS) provides images representative of the distribution of a specific ion within a sample surface. For the last fifteen years, concerted collaborative research to design a new ion microprobe with high technical standards in both mass and lateral resolution as well as in sensitivity has led to the CAMECA NanoSims 50, recently introduced onto the market. This instrument has decisive capabilities, which allow biological applications of SIMS microscopy at a level previously inaccessible. Its potential is illustrated here by the demonstration of the specific affinity of a melanoma marker for melanin. This finding is of great importance for the diagnosis and/or treatment of malignant melanoma, a tumour whose worldwide incidence is continuously growing. METHODS: The characteristics of the instrument are briefly described and an example of application is given. This example deals with the intracellular localization of an iodo-benzamide used as a diagnostic tool for the scintigraphic detection of melanic cells (e.g. metastasis of malignant melanoma). B16 melanoma cells were injected intravenously to C(57)BL(6)/J(1)/co mice. Multiple B16 melanoma colonies developed in the lungs of treated animals within three weeks. Iodobenzamide was injected intravenously in tumour bearing mice six hours before sacrifice. Small pieces of lung were prepared for SIMS analysis. RESULTS: Mouse lung B16 melanoma colonies were observed with high lateral resolution. Cyanide ions gave "histological" images of the cell, representative of the distribution of C and N containing molecules (e.g. proteins, nucleic acids, melanin, etc.) while phosphorus ions are mainly produced by nucleic acids. Iodine was detected only in melanosomes, confirming the specific affinity of the drug for melanin. No drug was found in normal lung tissue. CONCLUSION: This study demonstrates the potential of SIMS microscopy, which allows the study of ultra structural distribution of a drug within a cell. On the basis of our observations, drug internalization via membrane sigma receptors can be excluded

Characterizing Spatiotemporal Dynamics of Methane Emissions from Rice Paddies in Northeast China from 1990 to 2010

BACKGROUND: Rice paddies have been identified as major methane (CH(4)) source induced by human activities. As a major rice production region in Northern China, the rice paddies in the Three-Rivers Plain (TRP) have experienced large changes in spatial distribution over the recent 20 years (from 1990 to 2010). Consequently, accurate estimation and characterization of spatiotemporal patterns of CH₄ emissions from rice paddies has become an pressing issue for assessing the environmental impacts of agroecosystems, and further making GHG mitigation strategies at regional or global levels. METHODOLOGY/PRINCIPAL FINDINGS: Integrating remote sensing mapping with a process-based biogeochemistry model, Denitrification and Decomposition (DNDC), was utilized to quantify the regional CH(4) emissions from the entire rice paddies in study region. Based on site validation and sensitivity tests, geographic information system (GIS) databases with the spatially differentiated input information were constructed to drive DNDC upscaling for its regional simulations. Results showed that (1) The large change in total methane emission that occurred in 2000 and 2010 compared to 1990 is distributed to the explosive growth in amounts of rice planted; (2) the spatial variations in CH₄ fluxes in this study are mainly attributed to the most sensitive factor soil properties, i.e., soil clay fraction and soil organic carbon (SOC) content, and (3) the warming climate could enhance CH₄ emission in the cool paddies. CONCLUSIONS/SIGNIFICANCE: The study concluded that the introduction of remote sensing analysis into the DNDC upscaling has a great capability in timely quantifying the methane emissions from cool paddies with fast land use and cover changes. And also, it confirmed that the northern wetland agroecosystems made great contributions to global greenhouse gas inventory

Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Palliative care for the elderly - developing a curriculum for nursing and medical students

<p>Abstract</p> <p>Background</p> <p>Delivering palliative care to elderly, dying patients is a present and future challenge. In Germany, this has been underlined by a 2009 legislation implementing palliative care as compulsory in the medical curriculum. While the number of elderly patients is increasing in many western countries multimorbidity, dementia and frailty complicate care. Teaching palliative care of the elderly to an interprofessional group of medical and nursing students can help to provide better care as acknowledged by the ministry of health and its expert panels.</p> <p>In this study we researched and created an interdisciplinary curriculum focussing on the palliative care needs of the elderly which will be presented in this paper.</p> <p>Methods</p> <p>In order to identify relevant learning goals and objectives for the curriculum, we proceeded in four subsequent stages.</p> <p>We searched international literature for existing undergraduate palliative care curricula focussing on the palliative care situation of elderly patients; we searched international literature for palliative care needs of the elderly. The searches were sensitive and limited in nature. Mesh terms were used where applicable. We then presented the results to a group of geriatrics and palliative care experts for critical appraisal. Finally, the findings were transformed into a curriculum, focussing on learning goals, using the literature found.</p> <p>Results</p> <p>The literature searches and expert feedback produced a primary body of results. The following deduction domains emerged: Geriatrics, Palliative Care, Communication & Patient Autonomy and Organisation & Social Networks. Based on these domains we developed our curriculum.</p> <p>Conclusions</p> <p>The curriculum was successfully implemented following the Kern approach for medical curricula. The process is documented in this paper. The information given may support curriculum developers in their search for learning goals and objectives.</p

Genetic diversity of the African malaria vector Anopheles gambiae

The sustainability of malaria control in Africa is threatened by the rise of insecticide resistance in Anopheles mosquitoes, which transmit the disease1. To gain a deeper understanding of how mosquito populations are evolving, here we sequenced the genomes of 765 specimens of Anopheles gambiae and Anopheles coluzzii sampled from 15 locations across Africa, and identified over 50 million single nucleotide polymorphisms within the accessible genome. These data revealed complex population structure and patterns of gene flow, with evidence of ancient expansions, recent bottlenecks, and local variation in effective population size. Strong signals of recent selection were observed in insecticide-resistance genes, with several sweeps spreading over large geographical distances and between species. The design of new tools for mosquito control using gene-drive systems will need to take account of high levels of genetic diversity in natural mosquito populations

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Celecoxib (Celebrex®) was developed as a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of chronic pain. However, it now appears that this compound harbours additional pharmacologic activities that are entirely independent of its COX-2-inhibitory activity. This review presents the recently emerged direct non-COX-2 targets of celecoxib and their proposed role in mediating this drug's antitumour effects

How to improve medical education website design

<p>Abstract</p> <p>Background</p> <p>The Internet provides a means of disseminating medical education curricula, allowing institutions to share educational resources. Much of what is published online is poorly planned, does not meet learners' needs, or is out of date.</p> <p>Discussion</p> <p>Applying principles of curriculum development, adult learning theory and educational website design may result in improved online educational resources. Key steps in developing and implementing an education website include: 1) Follow established principles of curriculum development; 2) Perform a needs assessment and repeat the needs assessment regularly after curriculum implementation; 3) Include in the needs assessment targeted learners, educators, institutions, and society; 4) Use principles of adult learning and behavioral theory when developing content and website function; 5) Design the website and curriculum to demonstrate educational effectiveness at an individual and programmatic level; 6) Include a mechanism for sustaining website operations and updating content over a long period of time.</p> <p>Summary</p> <p>Interactive, online education programs are effective for medical training, but require planning, implementation, and maintenance that follow established principles of curriculum development, adult learning, and behavioral theory.</p

MET and AKT Genetic Influence on Facial Emotion Perception

Background: Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/ AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. Methods: One hundred and eighty two unrelated healthy volunteers (82 men and 100 women) were recruited. Four single nucleotide polymorphisms (SNP) of MET (rs2237717, rs41735, rs42336, and rs1858830) and AKT rs1130233 were genotyped and tested for their effects on facial emotion perception. Facial emotion perception was assessed by the face task of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Thorough neurocognitive functions were also assessed. Results: Regarding MET rs2237717, individuals with the CT genotype performed better in facial emotion perception than those with TT (p = 0.016 by ANOVA, 0.018 by general linear regression model [GLM] to control for age, gender, and education duration), and showed no difference with those with CC. Carriers with the most common MET CGA haplotype (frequency = 50.5%) performed better than non-carriers of CGA in facial emotion perception (p = 0.018, df = 1, F = 5.69, p = 0.009 by GLM). In MET rs2237717/AKT rs1130233 interaction, the C carrier/G carrier group showed better facial emotion perception than those with the TT/AA genotype (p = 0.035 by ANOVA, 0.015 by GLM), even when neurocognitive functions were controlled (p = 0.046 by GLM)