Antineoplastic activity of idazoxan hydrochloride

Idazoxan hydrochloride (IDA) is a 241 molecular weight imidazoline and adrenoreceptor ligand. It binds to mitochondrial membranes and promotes apoptosis of pancreatic beta cells. Since IDA has not been tested against tumor cells, the purpose of our study was to determine if IDA has antineoplastic activity. We used the conversion of a soluble tetrazolium salt to an insoluble formazan precipitate and differential staining cytotoxicity assays to determine if IDA was cytotoxic to cell lines of murine lung cancer and human prostate cancer, as well as to a variety of fresh human tumor samples. We used flow cytometry to analyze cell death and calreticulin expression. IDA is cytotoxic to both cell lines and against aliquots of specimens of breast, gastric, lung, ovarian and prostate cancers as well as non-Hodgkin’s lymphoma. It produces apoptotic cell death and promotes calreticulin expression, suggesting that IDA might be immunomodulatory in vivo. We anticipate that IDA will be clinically useful in cancer treatment

Selenium isotope evidence for progressive oxidation of the Neoproterozoic biosphere

Neoproterozoic (1,000–542 Myr ago) Earth experienced profound environmental change, including ‘snowball’ glaciations, oxygenation and the appearance of animals. However, an integrated understanding of these events remains elusive, partly because proxies that track subtle oceanic or atmospheric redox trends are lacking. Here we utilize selenium (Se) isotopes as a tracer of Earth redox conditions. We find temporal trends towards lower δ82/76Se values in shales before and after all Neoproterozoic glaciations, which we interpret as incomplete reduction of Se oxyanions. Trends suggest that deep-ocean Se oxyanion concentrations increased because of progressive atmospheric and deep-ocean oxidation. Immediately after the Marinoan glaciation, higher δ82/76Se values superpose the general decline. This may indicate less oxic conditions with lower availability of oxyanions or increased bioproductivity along continental margins that captured heavy seawater δ82/76Se into buried organics. Overall, increased ocean oxidation and atmospheric O2 extended over at least 100 million years, setting the stage for early animal evolution

Mentoring programs for medical students - a review of the PubMed literature 2000 - 2008

Abstract Background Although mentoring is acknowledged as a key to successful and satisfying careers in medicine, formal mentoring programs for medical students are lacking in most countries. Within the framework of planning a mentoring program for medical students at Zurich University, an investigation was carried out into what types of programs exist, what the objectives pursued by such programs are, and what effects are reported. Methods A PubMed literature search was conducted for 2000 - 2008 using the following keywords or their combinations: mentoring, mentoring program, medical student, mentor, mentee, protégé, mentorship. Although a total of 438 publications were identified, only 25 papers met the selection criteria for structured programs and student mentoring surveys. Results The mentoring programs reported in 14 papers aim to provide career counseling, develop professionalism, increase students' interest in research, and support them in their personal growth. There are both one-to-one and group mentorships, established in the first two years of medical school and continuing through graduation. The personal student-faculty relationship is important in that it helps students to feel that they are benefiting from individual advice and encourages them to give more thought to their career choices. Other benefits are an increase in research productivity and improved medical school performance in general. Mentored students also rate their overall well-being as higher. - The 11 surveys address the requirements for being an effective mentor as well as a successful mentee. A mentor should empower and encourage the mentee, be a role model, build a professional network, and assist in the mentee's personal development. A mentee should set agendas, follow through, accept criticism, and be able to assess performance and the benefits derived from the mentoring relationship. Conclusion Mentoring is obviously an important career advancement tool for medical students. In Europe, more mentoring programs should be developed, but would need to be rigorously assessed based on evidence of their value in terms of both their impact on the career paths of juniors and their benefit for the mentors. Medical schools could then be monitored with respect to the provision of mentorships as a quality characteristic.</p

Black race as a predictor of poor health outcomes among a national cohort of HIV/AIDS patients admitted to US hospitals: a cohort study

BACKGROUND: In general, the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) population has begun to experience the benefits of highly active antiretroviral therapy (HAART); unfortunately, these benefits have not extended equally to Blacks in the United States, possibly due to differences in patient comorbidities and demographics. These differences include rates of hepatitis B and C infection, substance use, and socioeconomic status. To investigate the impact of these factors, we compared hospital mortality and length of stay (LOS) between Blacks and Whites with HIV/AIDS while adjusting for differences in these key characteristics. METHODS: The 1996-2006 National Hospital Discharge Surveys were used to identify HIV/AIDS patients admitted to US hospitals. Survey weights were incorporated to provide national estimates. Patients < 18 years of age, those who left against medical advice, those with an unknown discharge disposition and those with a LOS < 1 day were excluded. Patients were stratified into subgroups by race (Black or White). Two multivariable logistic regression models were constructed with race as the independent variable and outcomes (mortality and LOS > 10 days) as the dependent variables. Factors that were significantly different between Blacks and Whites at baseline via bivariable statistical tests were included as covariates. RESULTS: In the general US population, there are approximately 5 times fewer Blacks than Whites. In the present study, 1.5 million HIV/AIDS hospital discharges were identified and Blacks were 6 times more likely to be hospitalized than Whites. Notably, Blacks had higher rates of substance use (30% vs. 24%; P < 0.001), opportunistic infections (27% vs. 26%; P < 0.001) and cocaine use (13% vs. 5%; P < 0.001). Conversely, fewer Blacks were co-infected with hepatitis C virus (8% vs. 12%; P < 0.001). Hepatitis B virus was relatively infrequent (3% for both groups). Crude mortality rates were similar for both cohorts (5%); however, a greater proportion of Blacks had a LOS > 10 days (21% vs. 19%; P < 0.001). Black race, in the presence of comorbidities, was correlated with a higher odds of LOS > 10 days (OR, 95% CI = 1.20 [1.10-1.30]), but was not significantly correlated with a higher odds of mortality (OR, 95% CI = 1.07 [0.93-1.25]). CONCLUSION: Black race is a predictor of LOS > 10 days, but not mortality, among HIV/AIDS patients admitted to US hospitals. It is possible that racial disparities in hospital outcomes may be closing with time

Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report

BACKGROUND: After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants. CASE PRESENTATION: The visual system recovery in an infant with perinatal stroke is assessed by combining diffusion tensor imaging (DTI) and event-related functional MRI (ER-fMRI). All experiments were done at 1.5T. A first DTI experiment was performed at 12 months of age. At 20 months of age, a second DTI experiment was performed and combined with an ER-fMRI experiment with visual stimuli (2 Hz visual flash). At 20 months of age, ER-fMRI showed significant negative activation in the visual cortex of the injured left hemisphere that was not previously observed in the same infant. DTI maps suggest recovery of the optic radiation in the vicinity of the lesion. Optic radiations in the injured hemisphere are more prominent in DTI at 20 months of age than in DTI at 12 months of age. CONCLUSION: Our data indicate that functional cortical recovery is supported by structural modifications that concern major pathways of the visual system. These neuroimaging findings might contribute to elaborate a pertinent strategy in terms of diagnosis and rehabilitation

De novo assembly of a transcriptome from the eggs and early embryos of Astropecten aranciacus

Starfish have been instrumental in many fields of biological and ecological research. Oocytes of Astropecten aranciacus, a common species native to the Mediterranean Sea and the East Atlantic, have long been used as an experimental model to study meiotic maturation, fertilization, intracellular Ca2+ signaling, and cell cycle controls. However, investigation of the underlying molecular mechanisms has often been hampered by the overall lack of DNA or protein sequences for the species. In this study, we have assembled a transcriptome for this species from the oocytes, eggs, zygotes, and early embryos, which are known to have the highest RNA sequence complexity. Annotation of the transcriptome identified over 32,000 transcripts including the ones that encode 13 distinct cyclins and as many cyclin-dependent kinases (CDK), as well as the expected components of intracellular Ca2+ signaling toolkit. Although the mRNAs of cyclin and CDK families did not undergo significant abundance changes through the stages from oocyte to early embryo, as judged by real-time PCR, the transcript encoding Mos, a negative regulator of mitotic cell cycle, was drastically reduced during the period of rapid cleavages. Molecular phylogenetic analysis using the homologous amino acid sequences of cytochrome oxidase subunit I from A. aranciacus and 30 other starfish species indicated that Paxillosida, to which A. aranciacus belongs, is not likely to be the most basal order in Asteroidea. Taken together, the first transcriptome we assembled in this species is expected to enable us to perform comparative studies and to design gene-specific molecular tools with which to tackle long-standing biological questions