Tickborne Pathogen Detection, Western Siberia, Russia

Ixodes and Dermacentor ticks harbor Borrelia, Anaplasma/Ehrlichia, Bartonella, and Babesia species

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

IMPROVEMENT OF THE ORGANIZATIONAL AND ECONOMIC MECHANISM OF ANTI-CRISIS MANAGEMENT AT INDUSTRIAL ENTERPRISES

The present paper deals with the issues of anti-crisis management of an industrial enterprise. Weprovide a clear definition of anti-crisis management and the key problems that hinder it. Within the framework of solving these problems, we have improved the organizational and economic mechanism of anti-crisis management of an industrial enterprise through a new approach to assessing the effectiveness of anti-crisis measures and using dynamic programming methods to form an anti-crisis program. The proposed mechanism is based on instant exclusion and fundamental diagnosis of the enterprise condition. The diagnosis lets reveal the reasons and prerequisites for the emergence of crisis situations, as well as the places of their possible occurrence, duration and complexity. We offer a list of measures as the next steps to overcome the crisis situations, to assess and compare them, and to form an effective anti-crisis program in the conditions of limited resources. The final stage consists in the implementation and monitoring of the designed anti-crisis program. We pay special attention to the evaluation of the effectiveness of anti-crisis measures. The expert method for evaluating the effectiveness of the anti-crisis measures has been further described in the paper, which makes it possible to obtain an integral assessment that takes into account not only economic, but also resource, social, environmental and production-technological components. This approach is especially relevant for large industrial enterprises, which are responsible for replenishing the budget, for ecology and social tension. This integral indicator lies at the basis of the economic and mathematical model of the formation of optimal anti-crisis program developed under the present research. We suggest using the maximum efficiency gain obtained after implementing one of the program measures per unit of invested funds as a criterion of optimality

Phosphate Record in Pleistocene-Holocene Sediments from Denisova Cave: Formation Mechanisms and Archaeological Implications

The distribution of authigenic phosphates in the sedimentary sequence of prehistoric Denisova Cave (Altai, South Siberia) has important archeological implications. The sampled Late Pleistocene&ndash;Early Holocene sedimentary sequence in the East Chamber of the cave consists of argilo-sandy-phosphatic sediments intercalated with guano layers of insectivorous bats. The sediments bear partially degraded N-rich organic matter (OM); chitin fragments enriched in S, P, Zn, and Cu; and a set of phosphates. The guano layers record at least three prolonged episodes of cave occupation by colonies of insectivorous bats between 10 kyr and 5 kyr BP, after people had left the cave or visited it rarely in small groups. The formation of phosphates follows the OM biodegradation pathways, with acidic leaching and gradual neutralization of P-rich solutions. The depth profile of authigenic phosphates shows a suite of mineral assemblages that mark a trend from acidic to slightly alkaline pH conditions of guano degradation (from top to bottom): ardealite, taranakite, and leucophosphite corresponding to acidic environments; whitlockite, brushite, and hydroxylapatite, which are stable under slightly acidic and neutral conditions; and hydroxylapatite in coexistence with calcite and stable at the bottom of the leaching profile under alkaline conditions. Authigenic phosphates can be used as reliable indicators of human non-occupation (abandonment) periods of Denisova Cave. Acidic leaching is responsible for disturbance and/or elimination of archaeological and paleontological materials in Late Pleistocene&ndash;Early Holocene sediments that were exposed to at least three &ldquo;acidic waves&rdquo;

The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1

Akt kinases mediate cell growth and survival. Here, we report that a pro-apoptotic kinase, Mst1/STK4, is a physiological Akt1 interaction partner. Mst1 was identified as a component of an Akt1 multiprotein complex isolated from lipid raft-enriched fractions of LNCaP human prostate cancer cells. Endogenous Mst1, along with its paralog, Mst2, acted as inhibitors of endogenous Akt1. Surprisingly, mature Mst1 as well as both of its caspase cleavage products, which localize to distinct subcellular compartments and are not structurally homologous, complexed with and inhibited Akt1. cRNAs encoding full-length Mst1, and N- and C-terminal caspase Mst1 cleavage products, reverted an early lethal phenotype in zebrafish development induced by expression of membrane-targeted Akt1. Mst1 and Akt1 localized to identical subcellular sites in human prostate tumors. Mst1 levels declined with progression from clinically localized to hormone refractory disease, coinciding with an increase in Akt activation with transition from hormone naïve to hormone-resistant metastases. These results position Mst1/2 within a novel branch of the phosphoinositide 3-kinase/Akt pathway and suggest an important role in cancer progression