Copper-Catalyzed Dehydrogenative Amidation of Light Alkanes

The functionalization of C-H bonds in light alkanes, particularly to form C-N bonds, remains a challenge. We report the dehydrogenative coupling of amides with C1–C4 hydrocarbons to form N-alkyl amide products with tBuOOtBu as oxidant, and a copper complex of a phenanthroline-type ligand as catalyst. The reactions occurred in good yields in benzene or supercritical carbon dioxide as solvents. This strategy allowed for the determination of the relative reactivity of these alkane C-H bonds toward this amination process and showed, in contrast to prior work with larger alkanes, that the reactivity correlated with bond dissociation energies.Support for this work was provided by the MINECO (CTQ2017-82893-C2-1-R), Junta de Andalucía (P18-RT-1536) and PO FEDER 2014–2020 (UHU-1260216). Work at UCB was supported by the Director, Office of Science, of the US Department of Energy under contract no. DE-AC02- 05CH11231. M.A.F. thanks MINECO for a Juan de la Cierva Incorporación fellowship. Funding for open access charges is given by Universidad de Huelva/ CBUA

The O3N2 and N2 abundance indicators revisited: improved calibrations based on CALIFA and T e-based literature data

Astronomy and Astrophysics 559 (2013): A114 reproduced with permission from Astronomy and AstrophysicsThe use of integral field spectroscopy is since recently allowing to measure the emission line fluxes of an increasingly large number of star-forming galaxies, both locally and at high redshift. Many studies have used these fluxes to derive the gas-phase metallicity of the galaxies by applying the so-called strong-line methods. However, the metallicity indicators that these datasets use were empirically calibrated using few direct abundance data points (Te-based measurements). Furthermore, a precise determination of the prediction intervals of these indicators is commonly lacking in these calibrations. Such limitations might lead to systematic errors in determining the gas-phase metallicity, especially at high redshift, which might have a strong impact on our understanding of the chemical evolution of the Universe. The main goal of this study is to review the most widely used empirical oxygen calibrations, O3N2 and N2, by using newdirect abundance measurements. We pay special attention to (1) the expected uncertainty of these calibrations as a function of the index value or abundance derived and (2) the presence of possible systematic offsets. This is possible thanks to the analysis of the most ambitious compilation of Te-based H ii regions to date. This new dataset compiles the Te-based abundances of 603 H ii regions extracted from the literature but also includes new measurements from the CALIFA survey. Besides providing new and improved empirical calibrations for the gas abundance, we also present a comparison between our revisited calibrations with a total of 3423 additional CALIFA H ii complexes with abundances derived using the ONS calibration from the literature. The combined analysis of T e-based and ONS abundances allows us to derive their most accurate calibration to date for both the O3N2 and N2 single-ratio indicators, in terms of all statistical significance, quality, and coverage of the parameters space. In particular, we infer that these indicators show shallower abundance dependencies and statistically significant offsets compared to others'. The O3N2 and N2 indicators can be empirically applied to derive oxygen abundances calibrations from either direct abundance determinations with random errors of 0.18 and 0.16, respectively, or from indirect ones (but based on a large amount of data), reaching an average precision of 0.08 and 0.09 dex (random) and 0.02 and 0.08 dex (systematic; compared to the direct estimations), respectivelyR.A. Marino is funded by the Spanish program of International Campus of Excellence Moncloa (CEI). D. Mast thank the Plan Nacional de Investigación y Desarrollo funding programs, AYA2012-31935 of the Spanish Ministerio de Economía y Competitividad, for the support given to this project. S.F.S thanks the the Ramón y Cajal project RyC-2011-07590 of the spanish Ministerio de Economía y Competitividad, for the support giving to this project. F.F.R.O. acknowledges the Mexican National Council for Science and Technology (CONACYT) for financial support under the program Estancias Postdoctorales y Sabáticas al Extranjero para la Consolidación de Grupos de Investigación, 2010-2012. We acknowledge financial support for the ESTALLIDOS collaboration by the Spanish Ministerio de Ciencia e Innovación under grant AYA2010- 21887-C04-03. BG-L also acknowledges support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AYA2012- 39408-C02-02. J.F.-B. acknowledges financial support from the Ramón y Cajal Program and grant AYA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as to the DAGAL network from the People’s Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7/2007-2013/ under REA grant agreement number PITN-GA-2011-289313. CK has been funded by project AYA2010-21887 from the Spanish PNAYA. P.P. acknowledges support by the Fundação para a Ciência e a Tecnologia (FCT) under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). R.M.G.D. and R.G.B. also acknowledge support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AyA2010-15081. V.S., L.G., and A.M.M. acknowledge financial support from the Fundação para a Ciência e a Tecnologia (FCT) under program Ciência 2008 and the research grant PTDC/CTE-AST/112582/200

Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)

Background Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities. Methods 1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC. Results Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10−6). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differsignificantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese). Conclusions In coronary patients, a metabolically abnormal phenotype is associated with a greater IMTCC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesit

Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer

Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ 2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment. Cancer Res; 77(9); 1-9. ©2017 AACR

Good practice regarding smoking cessation management in Spain: Challenges and opportunities for primary care physicians and nurses

INTRODUCTION We analyze the activities carried out by primary care (PC) physicians and nurses with respect to smoking cessation and evaluate their self-reported training, knowledge, and behavior. METHODS A cross-sectional study was conducted including 1514 PC physicians and nurses from June 2016 to March 2017, in Spain. The main variable was Good Practice (GP) in attention to smokers. To identify associated factors, a multilevel logistic regression model was used adjusted for sex, age, type of center, contract, years of employment, tobacco consumption, and self-reported training/knowledge. RESULTS Of the 792 physicians and 722 nurses, 48.6% referred to GP in smoking cessation management. The finding related to: being a non-smoker (OR=1.8; 95% CI: 1.2-2.5) or ex-smoker (OR= 1.4; 95% CI: 1.02-2.1), having a good level of knowledge (OR=1.8; 95% CI: 1.3-2.4) and training (OR=2.4; 95% CI: 1.8-3.2), and, to a lesser extent, being female (OR=1.3; 95% CI: 1.03-1.7), and work experience >10 years (OR=1.4; 95% CI: 1.03-1.9). The main GP barriers were: lack of time (45.5%), organizational problems (48.4%), and 35.4% lack of training. CONCLUSIONS The GP of PC physicians and nurses regarding smoking cessation management is related to being non-smokers or ex-smokers, and having sufficient training and knowledge. Lack of time and organizational problems were considered to be the main barriers. The promotion of training activities in the Spanish National Health Service with the support of scientific societies is required

Management and Outcome of Cardiac and Endovascular Cystic Echinococcosis

Cardiac and vascular involvement are infrequent in classical cystic echinococcosis (CE), but when they occur they tend to present earlier and are associated with complications that may be life threatening. Cardiovascular CE usually requires complex surgery, so in low-income countries the outcome is frequently fatal. This case series describes the characteristics of cardiovascular CE in patients diagnosed and treated at a Tropical Medicine & Clinical Parasitology Center in Spain. A retrospective case series of 11 patients with cardiac and/or endovascular CE, followed-up over a period of 15 years (1995–2009) is reported. The main clinical manifestations included thoracic pain or dyspnea, although 2 patients were asymptomatic. The clinical picture and complications vary according to cyst location. Isolated cardiac CE may be cured after surgery, while endovascular extracardiac involvement is associated with severe chronic complications. CE should be included in the differential diagnosis of cardiovascular disease in patients from endemic areas. CE is a neglected disease and further studies are necessary in order to make more definite management recommendations for this rare and severe form of the disease. The authors propose a general approach based on cyst location: exclusively cardiac, endovascular or both

EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation

Mitochondria are subcellular organelles critical for meeting the bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on genes and RNA species encoded both in the nucleus and mitochondria, as well as their coordinated translation, import and respiratory complex assembly. Here we describe the characterization of exonuclease domain like 2 (EXD2), a nuclear encoded gene that we show is targeted to the mitochondria and prevents the aberrant association of mRNAs with the mitochondrial ribosome. The loss of EXD2 resulted in defective mitochondrial translation, impaired respiration, reduced ATP production, increased reactive oxygen species and widespread metabolic abnormalities. Depletion of EXD2/CG6744 in D.melanogaster caused developmental delays and premature female germline stem cell attrition, reduced fecundity and a dramatic extension of lifespan that could be reversed with an anti-oxidant diet. Our results define a conserved role for EXD2 in mitochondrial translation that influences development and aging

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation