A new representation of acid-base disturbances

The acid-base status of intensive care patients is monitored on the basis of three quantities. The graphical representation which may be of help for the monitoring task is therefore cumbersome. The classical Siggaard-Andersen acid-base chart is such a representation, but it is only suited for evaluating one acid-base status at a time and not for representing acid-base paths. A new representation, obtained after a principal components transformation is presented. It is shown that the representation is characteristic for the laboratory instrument used. Its most attractive feature is that it is distortionless with respect to the three-dimensional configuration

Serum protein markers for the early detection of lung cancer:a focus on autoantibodies

Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and non-curable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Non-invasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early-stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential non-invasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. In this review we provide an overview of differentially expressed protein, antigen and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.</p

Effect of nitrous oxide on folate coenzyme distribution and de novo synthesis of thymidylate in human bone marrow cells

Abstract The effect of nitrous oxide on intracellular folate metabolism of the human bone marrow was studied in vitro. Bone marrow cells, obtained from healthy volunteers, were incubated with 5 × 10−8m-[3H]5-formyltetrahydrofolate (5-formylTHF) for 18 hr to label intracellular folate pools. Subsequently the cells were exposed to nitrous oxide for up to 10 hr, and the intracellular folate coenzyme levels were quantitated by HPLC. The dU suppression test was carried out on part of the bone marrow samples in order to measure folate-dependent synthesis of the DNA precursor thymidylate (dTMP). After 5 hr exposure to nitrous oxide the de novo dTMP synthesis of the bone marrow cells was significantly decreased (P < 0.05), and this reduced synthesis persisted at 10 hr. After both 5 and 10 hr of exposure to nitrous oxide the amount of 10-formylTHF was reduced (P < 0.05) while that of 5-methylTHF was increased (P < 0.05). At 10 hr the level of THF was also decreased (P < 0.05). This study shows that nitrous oxide exposure of human bone marrow cells causes a redistribution of the various folate coenzymes which supports the idea of ‘functional cobalamin deficiency’. Moreover it seems probable that following prolonged exposure to nitrous oxide, not only folate-dependent dTMP synthesis but also de novo purine synthesis is reduced

Portable blood gas and electrolyte analyzer evaluated in a multiinstitutional study

A recently introduced blood gas/electrolyte analyzer (SenDx 100((R)), renamed ABL70) intended for point-of-care, near-patient, or stat laboratory use was evaluated simultaneously in four different institutions and compared with three different laboratory bench analyzers with respect to imprecision, inaccuracy (assessed by tonometry), and patient-sample analyses. The analyzer is equipped with a sensor cassette and a reagent cartridge for 50, 100, or 200 analyses and 100 or more traditional quality-control measurements. One analysis requires 170 microL of whole blood and takes <90 s. Statistically, the instrument performed somewhat better (lower CVs) for PO2 and potassium and somewhat worse for pH, PCO2, and ionized calcium than the respective comparison analyzers. However, the overall performance (in terms of CV and accuracy) was satisfactory in terms of clinical (e.g., CLIA '88) goals in all institutions. The mean difference and the CV of that difference in some 400 patient-sample comparisons were as follows: 0.010 (+/- 0.002%) for pH, -0.65 mmHg (+/- 4%) for PCO2, -0.49 mmHg (+/- 6%) for Po2, 0.44 mmol/L (+/- 1.2%) for sodium, -0.013 mmol/L (+/- 2.9%) for potassium, -0.016 mmol/L (+/- 2.6%) for ionized calcium, and -0.016 L/L (+/- 7. 1%) for the hematocrit. Its acceptable analytical performance and ease of operation make the SenDx 100 suitable for the analysis of blood gases and electrolytes

Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P&lt;0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Anti-leukemic potential of methyl-cobalamin inactivation by nitrous oxide

Myelo‐cytotoxicity of extended nitrous oxide (N2O) inhalation was described almost forty years ago and then incidentally applied already with temporary success for suppressing leukemia. In 1948 the accompanying megaloblastic maturation arrest was explained by inactivation of the methylcobalamin coenzyme and subsequent folate deficiency. We studied the anti‐leukemic effect of N2O on a transplantable acute leukemia in B(rown) N(orway) rats. Progression of this B,N,M(yelocytic)L(eukemia) was measured as spleen and liver weights, and leukemic blood cell counts. The deoxyuridine (dU)‐suppression test provided in vitro indication of the functional folate activity of leukemic cells. Breathing of N2O‐oxygen considerably reduced but did not eradicate, BNML‐proliferation. Addition of anti‐metabolites, interfering with some enzyme in the folate metabolism beyond the methylcobalamin co‐enzyme dependent methionine synthase step, acted at least synergistically. The anti‐leukemic effect of cycloleucine, which reduces S‐adenosyl‐methionine synthesis by inactivation of methionine adenosyltransferase, was moderate but became much stronger with N2O inhalation. Methotrexate, a potent anti‐leukemic agent by inhibiting tetrahydrofolate (THF) generation through inactivation of di‐HF reductase, became highly anti‐BNML, even in low dosage when combined with or preceded by N2O. 5‐Fluorouracil, which inhibits methylene‐THF dependent thymidilate synthase, itself was surprisingly anti‐BNML, but also became much more potent with previous or concomittant N2O exposure. Preliminary dU‐suppression test results with human acute leukemia cells, exposed to N2O and/or folate antagonists in vitro, correlated well with the in vivo BNML‐experiments. Combining the anticobalamin activity of N2O with an anti‐folate therefore seems to be a promising chemotherapeutic approach. Copyrigh

Urbilaterian origin of paralogous GnRH and corazonin neuropeptide signalling pathways

This work was supported by funding from the China Scholarship Council (awarded to ST), Leverhulme Trust (grant RGP-2013-351, awarded to MRE), BBSRC (grant BB/M001644/1 awarded to MRE; grant BB/M001032/1 awarded to JHS) and a Company of Biologists (Journal of Experimental Biology) Travelling Fellowship awarded to MZ. IB is supported by a postdoctoral fellowship from the Research Foundation–Flanders (FWO)

The cost of emission mitigation by legume crops in French agriculture

Transplantation and immunomodulatio

Estimated Worldwide Mortality Attributed to Secondhand Tobacco Smoke Exposure, 1990-2016

Importance: The World Health Organization estimates that the 1 billion individuals who smoke worldwide contribute to the 880 000 secondhand smoke (SHS)-related deaths among individuals who do not smoke each year. A better understanding of the scale of harm of SHS to those who do not smoke could increase awareness of the consequences of smoking and help to design measures to protect individuals who do not smoke, especially children. Objective: To calculate the number of individuals who smoke associated with the death of 1 individual who died of SHS exposure both on a global scale and in various World Bank regions. Design, Setting, and Participants: In this cross-sectional epidemiologic assessment, data from Our World in Data were used to tabulate the number of individuals who smoke in each country and number of premature deaths related to SHS in that country from 1990 to 2016. The mean number of cigarettes consumed in all countries was also included in analyses. Data were collected for the following World Bank regions: North America, Latin America and the Caribbean, Europe and Central Asia, the Middle East and North Africa, sub-Saharan Africa, South Asia, and East Asia and the Pacific from 1990 and 2016. Statistical analysis was conducted in July 2019. Exposure: Secondhand smoke. Main Outcomes and Measures: The pack-year index, calculated as the number of pack-years associated with the death of 1 individual who does not smoke but was exposed to SHS, and the SHS index, calculated as the number of individuals who smoked for 24 years (ie, the mean duration of smoking) associated with the death of 1 individual who does not smoke. Results: Globally, the SHS index changed favorably, from 31.3 (95% CI, 30.6-32.0) individuals who smoked associated with the death of 1 individual who did not smoke in 1990 to 52.3 (95% CI, 51.2-53.5) individuals who smoked in 2016. There was a wide regional variation in the 2016 secondhand smoke index, from 42.6 (95% CI, 41.6-43.5) individuals who smoked in the Middle East and North Africa to 85.7 (95% CI, 83.8-87.7) individuals who smoked in North America. Worldwide, the pack-year index also changed favorably from 751.9 (95% CI, 736.3-770.7) pack-years associated with 1 death in 1990 to 1255.9 (95% CI, 1227.2-1284.4) pack-years in 2016. Conclu