Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria (AKI UO). We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC) and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78). The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89), which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02) and PC levels independently predicted mortality/non-renal recovery (p=0.04). In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI

Monoclonal antibodies raised against 167-180 aa sequence of human carbonic anhydrase XII inhibit its enzymatic activity

Abstract Human carbonic anhydrase XII (CA XII) is a single-pass transmembrane protein with an extracellular catalytic domain. This enzyme is being recognized as a potential biomarker for different tumours. The current study was aimed to generate monoclonal antibodies (MAbs) neutralizing the enzymatic activity of CA XII. Bioinformatics analysis of CA XII structure revealed surface-exposed sequences located in a proximity of its catalytic centre. Two MAbs against the selected antigenic peptide spanning 167-180 aa sequence of CA XII were generated. The MAbs were reactive with recombinant catalytic domain of CA XII expressed either in E. coli or mammalian cells. Inhibitory activity of the MAbs was demonstrated by a stopped flow CO2 hydration assay. The study provides new data on the surface-exposed linear CA XII epitope that may serve as a target for inhibitory antibodies with a potential immunotherapeutic application

Reaction of Chlorine Molecules with Unsaturated Submicron Organic Particles

The reaction of closed shell Cl2 molecules with sub-micron droplets composed of unsaturated molecules, oleic acid (OA), linoleic acid (LA), linolenic acid (LNA), or squalene (Sqe), are investigated in an atmospheric pressure flow tube reactor in conjunction with a vacuum ultraviolet photoionization aerosol mass spectrometer and a scanning mobility particle sizer. Cl2 is found to react with all particles, and the reactive uptake coefficients depend on the number of unsaturated reaction sites, e.g., γCl2Sqe = (0.66 ± 0.03) × 10-4 versus γCl2OA = (0.23 ± 0.01) × 10-4. In addition, the chemical evolution of squalene and its chlorinated products reveal that the reaction becomes slower for higher chlorinated products

Continued Slow Decay of the Residual Plasma Viremia Level in HIV-1 – Infected Adults Receiving Long-term Antiretroviral Therapy

We measured plasma human immunodeficiency virus type 1 (HIV-1) RNA levels by means of single-copy assay in 334 participants receiving virologically suppressive antiretroviral therapy (ART). A residual viremia load of ≥1 copy/mL after 4 years of ART was predicted by a higher pre-ART HIV-1 RNA level, higher CD8+ T-cell count during treatment, and a lower ratio of CD4+ T cells to CD8+ T cells during treatment but not by initial ART regimen. In a longitudinal subset of 64 individuals, continued decay of the plasma HIV-1 RNA level was observed, with an average annual decrease of 6% and an estimated half-life of 11.5 years. In contrast to prior reports, the persistent viremia level continues to slowly decline during years 4–12 of suppressive ART

Twilight observations suggest unknown sources of HO_x

Measurements of the concentrations of OH and HO_(2) (HO_(x)) in the high-latitude lower stratosphere imply the existence of unknown photolytic sources of HO_(x). The strength of the additional HO_(x) source required to match the observations depends only weakly on solar zenith angle (SZA) for 80° < SZA < 93°. The wavelengths responsible for producing this HO_(x) must be longer than 650 nm because the flux at shorter wavelengths is significantly attenuated at high SZA by scattering and absorption. Provided that the sources involve only a single photon, the strength of the bonds being broken must be < 45 kcal mole^(−1). We speculate that peroxynitric acid (HNO_4) dissociates after excitation to an unknown excited state with an integrated band cross section of 2-3 × 10^(−20) cm^(2) molecule^(−1) nm (650 < λ < 1250 nm)

КЛІНІЧНИЙ ВИПАДОК ПОДВОЄННЯ ПРАВОЇ НИРКОВОЇ АРТЕРІЇ, УСКЛАДНЕНИЙ КОМПРЕСІЄЮ ТА ТРОМБОЗОМ ПРАВОЇ НИРКОВОЇ ВЕНИ, ФЛОТУЮЧИМ ТРОМБОЗОМ НИЖНЬОЇ ПОРОЖНИСТОЇ ВЕНИ

Summary. Patient K., apply to Ternopil University Hospital with complaints of hematuria and intermittent low back pain. Complaints were noted in the last two days, for the first time. During examination of patient limb edema was detected. Laboratory indexes: general blood tests and electrocardiogram – without pathological changes. Cystourethroscopy, no pathology was detected. According to ultrasonographic examination of the abdomen, retroperitoneal organs, lower extremities, no pathological changes were detected. Computed tomography with contrast of the vessels of the abdominal organs was performed. Doubling of the right renal artery with an atypical abnormal location of the accessory artery was revealed. As a result of the conducted diagnosis of diseases the patient was able to establish a congenital anomaly development of the arterial system of the right kidney which caused compression of the right renal vein, and ectasia, venous stasis of blood and the phenomenon of phlebohypertension in the right kidney, which, in fact, caused hematuria. Venous stasis caused thrombosis with progression of thrombosis to the vena cava inferior with flotation into the lumen. Considering the fact of flotation with the spread of thrombotic masses in the inferior vena cava, the method of treatment is surgery – thrombectomy of the right renal and vena cava inferior.РЕЗЮМЕ. Больной К. обратился в Тернопольскую университетскую больницу с жалобами на гематурию и периодические боли в пояснице. Жалобы возникли за последние два дня впервые. При осмотре у больного обнаружен отек конечностей. Лабораторные показатели – общие анализы крови и электрокардиограмма – без патологических изменений. При проведении цистоуретроскопии патологии не выявлено. По данным УЗИ брюшной полости, забрюшинных органов, нижних конечностей патологических изменений не выявлено. Выполнена компьютерная томография с контрастированием сосудов органов брюшной полости. Выявлено удвоение правой почечной артерии с атипичным патологическим расположением добавочной артерии. В результате проведенной диагностики у пациента удалось установить врожденную аномалию развития артериальной системы правой почки, вызвавшую сдавление правой почечной вены, ее эктазию, венозный застой крови и явления флебогипертензии в правой почке, которое, собственно, и вызвало гематурию. Венозный застой вызвал тромбоз с прогрессированием тромбоза в нижнюю полую вену с флотацией в ее просвет. Учитывая факт флотации с распространением тромботических масс в нижнюю полую вену, методом лечения избрано оперативное вмешательство – тромбэктомия из правой почечной и нижней полой вен.РЕЗЮМЕ. Пацієнт К. звернувся в Тернопільську університетську лікарню зі скаргами на гематурію та періодичний біль у попереку, які з’явилися протягом останніх двох днів, вперше. При об’єктивному фізикальному обстеженні виявлено пастозність шкірних покривів та виражений набряк обох нижніх кінцівок. Лабораторні показники – загальний, біохімічний аналізи крові, коагулограма та електрокардіограма – без патологічних змін. Наявна макрогематурія. При проведенні цистоуретроскопії патології не виявлено. За даними ультрасонографічного обстеження живота, органів заочеревинного простору, нижніх кінцівок патологічних змін не виявлено. Проведено комп’ютерну томографію з контрастуванням судинного русла органів черевної порожнини, в результаті якої виявлено подвоєння правої ниркової артерії з нетиповим аномальним розташуванням додаткової артерії. У результаті проведеної діагностики захворювання у пацієнта вдалось встановити вроджену аномалію розвитку артеріальної системи правої нирки, що спричинила компресію правої ниркової вени, її ектазію, венозний стаз крові та явища флебогіпертензії у правій нирці, що, власне, і стало причиною гематурії. Саме венозний стаз і спричинив тромбоутворення із прогресуванням тромбозу на нижню порожнисту вену з флотацією в її просвіт. Враховуючи явища флотації з поширенням тромботичних мас у нижню порожнисту вену, методом лікування обрано оперативне втручання – тромбектомію з правої ниркової та нижньої порожнистої вен

Crosssectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients.

ABSTRACT Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. We present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire of adherence to antiretroviral (ARV) therapy. Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ARV therapy, motivation to adhere to treatment, and behavioral skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ARV regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ARV regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The PMAQ had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the PMAQ to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of antiretroviral therapy, 80% were failing or had previously failed the ARV treatment. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ARV therapy, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure

Photolysis of sulphuric acid as the source of sulphur oxides in the mesosphere of Venus

The sulphur cycle plays fundamental roles in the chemistry and climate of Venus. Thermodynamic equilibrium chemistry at the surface of Venus favours the production of carbonyl sulphide and to a lesser extent sulphur dioxide. These gases are transported to the middle atmosphere by the Hadley circulation cell. Above the cloud top, a sulphur oxidation cycle involves conversion of carbonyl sulphide into sulphur dioxide, which is then transported further upwards. A significant fraction of this sulphur dioxide is subsequently oxidized to sulphur trioxide and eventually reacts with water to form sulphuric acid. Because the vapour pressure of sulphuric acid is low, it readily condenses and forms an upper cloud layer at altitudes of 60–70 km, and an upper haze layer above 70 km (ref. 9), which effectively sequesters sulphur oxides from photochemical reactions. Here we present simulations of the fate of sulphuric acid in the Venusian mesosphere based on the Caltech/JPL kinetics model, but including the photolysis of sulphuric acid. Our model suggests that the mixing ratios of sulphur oxides are at least five times higher above 90 km when the photolysis of sulphuric acid is included. Our results are inconsistent with the previous model results but in agreement with the recent observations using ground-based microwave spectroscopy and by Venus Express

A Single Gene Target of an ETS-Family Transcription Factor Determines Neuronal CO2-Chemosensitivity

Many animals possess neurons specialized for the detection of carbon dioxide (CO2), which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO2. The ETS-5 transcription factor is necessary for the specification of CO2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO2-detection and transforms neurons into CO2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO2-sensing neurons in other phyla