The Great Eruption of Eta Carinae

During the years 1838-1858, the very massive star {\eta} Carinae became the prototype supernova impostor: it released nearly as much light as a supernova explosion and shed an impressive amount of mass, but survived as a star.1 Based on a light-echo spectrum of that event, Rest et al.2 conclude that "a new physical mechanism" is required to explain it, because the gas outflow appears cooler than theoretical expectations. Here we note that (1) theory predicted a substantially lower temperature than they quoted, and (2) their inferred observational value is quite uncertain. Therefore, analyses so far do not reveal any significant contradiction between the observed spectrum and most previous discussions of the Great Eruption and its physics.Comment: To appear in Nature, a brief communication arising in response to Rest et al. 2012. Submitted to Nature February 17, 201

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Dopamine agonists and ischemic complications in Parkinson’s disease: a nested case–control study

Personalised Therapeutic

Validation of the MEDFICTS dietary questionnaire: A clinical tool to assess adherence to American Heart Association dietary fat intake guidelines

BACKGROUND: Dietary assessment tools are often too long, difficult to quantify, expensive to process, and largely used for research purposes. A rapid and accurate assessment of dietary fat intake is critically important in clinical decision-making regarding dietary advice for coronary risk reduction. We assessed the validity of the MEDFICTS (MF) questionnaire, a brief instrument developed to assess fat intake according to the American Heart Association (AHA) dietary "steps". METHODS: We surveyed 164 active-duty US Army personnel without known coronary artery disease at their intake interview for a primary prevention cardiac intervention trial using the Block food frequency (FFQ) and MF questionnaires. Both surveys were completed on the same intake visit and independently scored. Correlations between each tools' assessment of fat intake, the agreement in AHA step categorization of dietary quality with each tool, and the test characteristics of the MF using the FFQ as the gold standard were assessed. RESULTS: Subjects consumed a mean of 36.0 ± 13.0% of their total calories as fat, which included saturated fat consumption of 13.0 ± 0.4%. The majority of subjects (125/164; 76.2%) had a high fat (worse than AHA Step 1) diet. There were significant correlations between the MF and the FFQ for the intake of total fat (r = 0.52, P < 0.0001) and saturated fat (r = 0.52, P < 0.0001). Despite these modest correlations, the currently recommended MF cutpoints correctly identified only 29 of 125 (23.3%) high fat (worse than AHA Step 1) diets. Overall agreement for the AHA diet step between the FFQ and MF (using the previously proposed MF score cutoffs of 0–39 [AHA Step 2], 40–70 [Step 1], and >70 [high fat diet]) was negligible (kappa statistic = 0.036). The MF was accurate at the extremes of fat intake, but could not reliably identify the 3 AHA dietary classifications. Alternative MF cutpoints of <30 (Step 2), 30–50 (Step 1), and >50 (high fat diet) were highly sensitive (96%), but had low specificity (46%) for a high fat diet. ROC curve analysis identified that a MF score cutoff of 38 provided optimal sensitivity 75% and specificity 72%, and had modest agreement (kappa = 0.39, P < 0.001) with the FFQ for the identification of subjects with a high fat diet. CONCLUSIONS: The MEDFICTS questionnaire is most suitable as a tool to identify high fat diets, rather than discriminate AHA Step 1 and Step 2 diets. Currently recommended MEDFICTS cutpoints are too high, leading to overestimation of dietary quality. A cutpoint of 38 appears to be providing optimal identification of patients who do not meet AHA dietary guidelines for fat intake

Influenza Virus Infection of the Murine Uterus: A New Model for Antiviral Immunity in the Female Reproductive Tract

Secretory IgA (S-IgA) mediates local immunity to influenza virus in the murine upper respiratory tract and may play an important role in local immunity to various microorganisms in the female reproductive tract as well. Although the presence of IgA in cervicovaginal or uterine secretions has been correlated with immunity to a number of pathogens, there has been no direct demonstration of the mediation of uterine antiviral immunity by S-IgA. Influenza virus, although not a normal pathogen of the reproductive tract, was used to develop a model for the investigation of mucosal immunity in the uterus. PR8 (H1N1) influenza virus injected into the ovarian bursa of BALB/c mice grew well, with peak titers between days 3 and 5. Intravenous injection of polymeric IgA anti-influenza virus monoclonal antibody before or 30 min after viral challenge protected mice against viral infection. We believe this work to be the first direct demonstration of S-IgA-mediated antiviral uterine immunity. It provides a model for further investigation of immunity in the female reproductive tract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63226/1/vim.2006.19.613.pd

Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

The advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase, 5HT3 antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK1 antagonists) belong to a new class of antiemetic agents that specifically target the NK1 receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK1 antagonists to dual therapy with a 5HT3 antagonist plus dexamethasone improves the acute emesis protection by a further 10-15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20-30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled

Microencapsulated foods as a functional delivery vehicle for omega-3 fatty acids: a pilot study

It is well established that the ingestion of the omega-3 (N3) fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) positively benefit a variety of health indices. Despite these benefits the actual intake of fish derived N3 is relatively small in the United States. The primary aim of our study was to examine a technology capable of delivering omega-3 fatty acids in common foods via microencapsulation (MicroN3) in young, healthy, active participants who are at low risk for cardiovascular disease. Accordingly, we randomized 20 participants (25.4 ± 6.2 y; 73.4 ± 5.1 kg) to receive the double blind delivery of a placebo-matched breakfast meal (~2093 kJ) containing MicroN3 (450–550 mg EPA/DHA) during a 2-week pilot trial. Overall, we observed no differences in overall dietary macronutrient intake other than the N3 delivery during our treatment regimen. Post-test ANOVA analysis showed a significant elevation in mean (SE) plasma DHA (91.18 ± 9.3 vs. 125.58 ± 11.3 umol/L; P < 0.05) and a reduction in triacylglycerols (89.89 ± 12.8 vs. 80.78 ± 10.4 mg/dL; P < 0.05) accompanying the MicroN3 treatment that was significantly different from placebo (P < 0.05). In post study interviews, participants reported that the ingested food was well-tolerated, contained no fish taste, odor or gastrointestinal distress accompanying treatment. The use of MicroN3 foods provides a novel delivery system for the delivery of essential fatty acids. Our study demonstrates that MicroN3 foods promote the absorption of essential N3, demonstrate bioactivity within 2 weeks of ingestion and are well tolerated in young, active participants who are at low risk for cardiovascular disease

Comparing the Epidermal Growth Factor Interaction with Four Different Cell Lines: Intriguing Effects Imply Strong Dependency of Cellular Context

The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of 125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®

Rapid Reactivation of Extralymphoid CD4 T Cells during Secondary Infection

After infection, extralymphoid tissues are enriched with effector and memory T cells of a highly activated phenotype. The capacity for rapid effector cytokine response from extralymphoid tissue-memory T cells suggests these cells may perform a ‘sentinel’ function in the tissue. While it has been demonstrated that extralymphoid CD4+ T cells can directly respond to secondary infection, little is known about how rapidly this response is initiated, and how early activation of T cells in the tissue may affect the innate response to infection. Here we use a mouse model of secondary heterosubtypic influenza infection to show that CD4+ T cells in the lung airways are reactivated within 24 hours of secondary challenge. Airway CD4+ T cells initiate an inflammatory cytokine and chemokine program that both alters the composition of the early innate response and contributes to the reduction of viral titers in the lung. These results show that, unlike a primary infection, extralymphoid tissue-memory CD4+ T cells respond alongside the innate response during secondary infection, thereby shaping the overall immune profile in the airways. These data provide new insights into the role of extralymphoid CD4+ T cells during secondary immune responses

Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics

Objective Nausea and vomiting are the most distressful side effects of cytotoxic drugs in cancer patients. Antiemetics are commonly used to reduce these side effects. However, the current antiemetic efficacy is about 70–80% in patients treated with highly-emetogenic cytotoxic drugs. One of the potential factors explaining this suboptimal response is variability in genes encoding enzymes and proteins which play a role in metabolism, transport and receptors related to antiemetic drugs. Aim of this review was to describe the pharmacology and pharmacogenetic concepts of of antiemetics in oncology. Method Pharmacogenetic and pharmacology studies of antiemetics in oncology published between January 1997 and February 2010 were searched in PubMed. Furthermore, related textbooks were also used for exploring the pharmacology of antiemetic drugs. The antiemetic drugs which were searched were the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs), dopamine antagonists, corticosteroids, benzodiazepines, cannabinoids, antihistamines and neurokinin-1 antagonists. Result The 5-HT3RAs are widely used in highly emetogenic chemotherapy in combination with dexamethasone and a neurokinin-1 antagonist, especially in acute phase. However, the dopamine antagonists and benzodiazepines were found more appropriate for use in breakthrough and anticipatory symptoms or in preventing the delayed phase of chemotherapy induced nausea and vomiting. The use of cannabinoids and antihistamines need further investigation. Only six articles on pharmacogenetics of the 5-HT3RAs in highly emetogenic chemotherapy are published. Specifically, these studies investigated the association of the efficacy of 5-HT3RAs and variants in the multi drug resistance 1 (MDR1) gene, 5-HT3A,B and C receptor genes and CYP2D6 gene. The pharmacogenetic studies of the other antiemetics were not found in this review. Conclusion It is concluded that pharmacogenetic studies with antiemetics are sparse. It is too early to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice: confirmation of early findings is required