Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma

We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Fatal cerebral edema associated with serine deficiency in CSF

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study

BACKGROUND: Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide) has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. METHODS: The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. RESULTS: Of 149 microbiologically evaluable patients, 57 (9 bacteremic) had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic) were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%), Moraxella catarrhalis (100%), Staphylococcus aureus (80%), and Legionella spp. (100%). The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%). In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1%) and nausea (5.8%). CONCLUSION: Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae

Towards a typology for constrained climate model forecasts

In recent years several methodologies have been developed to combine and interpret ensembles of climate models with the aim of quantifying uncertainties in climate projections. Constrained climate model forecasts have been generated by combining various choices of metrics used to weight individual ensemble members, with diverse approaches to sampling the ensemble. The forecasts obtained are often significantly different, even when based on the same model output. Therefore, a climate model forecast classification system can serve two roles: to provide a way for forecast producers to self-classify their forecasts; and to provide information on the methodological assumptions underlying the forecast generation and its uncertainty when forecasts are used for impacts studies. In this review we propose a possible classification system based on choices of metrics and sampling strategies. We illustrate the impact of some of the possible choices in the uncertainty quantification of large scale projections of temperature and precipitation changes, and briefly discuss possible connections between climate forecast uncertainty quantification and decision making approaches in the climate change context

I-Motif Structures Formed in the Human c-MYC Promoter Are Highly Dynamic–Insights into Sequence Redundancy and I-Motif Stability

The GC-rich nuclease hypersensitivity element III1 (NHE III1) of the c-MYC promoter largely controls the transcriptional activity of the c-MYC oncogene. The C-rich strand in this region can form I-motif DNA secondary structures. We determined the folding pattern of the major I-motif formed in the NHE III1, which can be formed at near-neutral pH. While we find that the I-motif formed in the four 3′ consecutive runs of cytosines appears to be the most favored, our results demonstrate that the C-rich strand of the c-MYC NHE III1 exhibits a high degree of dynamic equilibration. Using a trisubstituted oligomer of this region, we determined the formation of two equilibrating loop isomers, one of which contains a flipped-out cytosine. Our results indicate that the intercalative cytosine+–cytosine base pairs are not always necessary for an intramolecular I-motif. The dynamic character of the c-MYC I-motif is intrinsic to the NHE III1 sequence and appears to provide stability to the c-MYC I-motif

Elevated Non-Esterified Fatty Acid Concentrations during Bovine Oocyte Maturation Compromise Early Embryo Physiology

Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte maturation affect the development and physiology of zygotes formed from such oocytes, using the cow as a model. The zygotes were grown to blastocysts, which were evaluated for their quality in terms of cell number, apoptosis, expression of key genes, amino acid turnover and oxidative metabolism. Oocyte maturation under elevated NEFA concentrations resulted in blastocysts with significantly lower cell number, increased apoptotic cell ratio and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up-regulated lactate consumption and higher amino acid metabolism. These data indicate that exposure of maturing oocytes to elevated NEFA concentrations has a negative impact on fertility not only through a reduction in oocyte developmental capacity but through compromised early embryo quality, viability and metabolism

Assessment of Daily Life Physical Activities in Pulmonary Arterial Hypertension

Background: In pulmonary arterial hypertension (PAH), the six-minute walk test (6MWT) is believed to be representative of patient’s daily life physical activities (DLPA). Whether DLPA are decreased in PAH and whether the 6MWT is representative of patient’s DL PA remain unknown. Methods: 15 patients with idiopathic PAH (IPAH) and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc) were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH. Each subject completed a 6MWT. The mean number of daily steps and the mean energy expenditure and duration of physical activities.3 METs were assessed with a physical activity monitor for seven consecutive days and used as markers of DLPA. Results: The mean number of daily steps and the mean daily energy expenditure and duration of physical activities.3 METs were all reduced in PAH patients compared to their controls (all p,0.05). The mean number of daily steps correlated with the 6MWT distance for both IPAH and PAH-SSc patients (r = 0.76, p,0.01 and r = 0.85, p,0.01), respectively. Conclusion: DLPA are decreased in PAH and correlate with the 6MWT distance. Functional exercise capacity may thus be a useful surrogate of DL PA in PAH

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente