Особливості синтаксичної організації художньої прози Редьярда Кіплінга

Статья посвящена исследованию синтаксических конструкций, с помощью которых в художественной прозе Редьярда Киплинга отображаются особенности английской и индийской культур.Стаття присвячена дослідженню синтаксичних конструкцій, за допомогою яких у художній прозі Редьярда Кіплінга відображено особливості англійської та індійської культур.The article is dedicated to the investigation of the main syntactic constractions with the help of which in the prose of Rudyard Kipling there are depicted the peculiarities of English and Indian cultures

On the Origin of Regioselectivity in Palladium-Catalyzed Oxidation of Glucosides

The palladium-catalyzed oxidation of glucopyranosides has been investigated using relativistic density functional theory (DFT) at ZORA-BLYP−D3(BJ)/TZ2P. The complete Gibbs free energy profiles for the oxidation of secondary hydroxy groups at C2, C3, and C4 were computed for methyl β-glucoside and methyl carba-β-glucoside. Both computations and oxidation experiments on carba-glucosides demonstrate the crucial role of the ring oxygen in the C3 regioselectivity observed during the oxidation of glucosides. Analysis of the model systems for oxidized methyl β-glucoside shows that the C3 oxidation product is intrinsically favored in the presence of the ring oxygen. Subsequent energy decomposition analysis (EDA) and Hirschfeld charge analysis reveal the role of the ring oxygen: it positively polarizes C1/C5 by inductive effects and disfavors any subsequent buildup of positive charge at neighboring carbon atoms, rendering C3 the most favored site for the β-hydride elimination

Prolonged antibiotic prophylaxis after pancreatoduodenectomy:systematic review and meta-analysis

Background: Previous studies have reported conflicting results of prolonged antibiotic prophylaxis on infectious complications after pancreatoduodenectomy. This study evaluated the effect of prolonged antibiotics on surgical-site infections (SSIs) after pancreatoduodenectomy. Methods: A systematic review and meta-analysis was undertaken of SSIs in patients with perioperative (within 24 h) versus prolonged antibiotic (over 24 h) prophylaxis after pancreatoduodenectomy. SSIs were classified as organ/space infections or superficial SSI within 30 days after surgery. ORs were calculated using a Mantel–Haenszel fixed-effect model.Results:Ten studies were included in the qualitative analysis, of which 8 reporting on 1170 patients were included in the quantitative analysis. The duration of prolonged antibiotic prophylaxis varied between 2 and 10 days after surgery. Four studies reporting on 782 patients showed comparable organ/space infection rates in patients receiving perioperative and prolonged antibiotics (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, among patients with preoperative biliary drainage (5 studies reporting on 577 patients), organ/space infection rates were lower with prolonged compared with perioperative antibiotics (OR 2.09, 1.43 to 3.07). Three studies (633 patients) demonstrated comparable superficial SSI rates between patients receiving perioperative versus prolonged prophylaxis (OR 1.54, 0.97 to 2.44), as well as in patients with preoperative biliary drainage in 4 studies reporting on 431 patients (OR 1.60, 0.89 to 2.88). Conclusion: Prolonged antibiotic prophylaxis is associated with fewer organ/space infection in patients who undergo preoperative biliary drainage. However, the optimal duration of antibiotic prophylaxis after pancreatoduodenectomy remains to be determined and warrants confirmation in an RCT.</p

Renal Handling of Galectin-3 in the General Population, Chronic Heart Failure, and Hemodialysis

Background-Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF. Methods and Results-In Sprague-Dawley rats, we infused galectin-3 and studied distribution and renal clearance. Furthermore, galectin-3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin-3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin-3. Plasma galectin-3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P Conclusions-In this small cross-sectional study, we report that urine levels of galectin-3 are not increased in HF patients, despite substantially increased plasma galectin-3 levels. The impaired renal handling of galectin-3 in patients with HF may explain the described relation between renal function and galectin-3 and may account for the elevated plasma galectin-3 in HF

Early Trajectory Prediction in Elite Athletes

Cerebellar plasticity is a critical mechanism for optimal feedback control. While Purkinje cell activity of the oculomotor vermis predicts eye movement speed and direction, more lateral areas of the cerebellum may play a role in more complex tasks, including decision-making. It is still under question how this motor-cognitive functional dichotomy between medial and lateral areas of the cerebellum plays a role in optimal feedback control. Here we show that elite athletes subjected to a trajectory prediction, go/no-go task manifest superior subsecond trajectory prediction accompanied by optimal eye movements and changes in cognitive load dynamics. Moreover, while interacting with the cerebral cortex, both the medial and lateral cerebellar networks are prominently activated during the fast feedback stage of the task, regardless of whether or not a motor response was required for the correct response. Our results show that cortico-cerebellar interactions are widespread during dynamic feedback and that experience can result in superior task-specific decision skills

The development of non-hydrolysable oligosaccharide activity-based inactivators for endoglycanases : a case study on a-1,6 mannanases

There is a vast genomic resource for enzymes active on carbohydrates. Lagging far behind, however, are functional chemical tools for the rapid characterization of carbohydrate-active enzymes. Activity-based probes (ABPs) offer one chemical solution to these issues with ABPs based upon cyclophellitol epoxide and aziridine covalent and irreversible inhibitors representing a potent and widespread approach. Such inhibitors for enzymes active on polysaccharides are potentially limited by the requirement for several glycosidic bonds, themselves substrates for the enzyme targets. Here, it is shown that non-hydrolysable trisaccharide can be synthesized and applied even to enzymes with challenging subsite requirements. It was found that incorporation of carbasugar moieties, which was accomplished by cuprate-assisted regioselective trans-diaxial epoxide opening of carba-mannal synthesised for this purpose, yields inactivators that act as powerful activity-based inhibitors for alpha-1,6 endo-mannanases. 3-D structures at 1.35-1.47 angstrom resolutions confirm the design rationale and binding to the enzymatic nucleophile. Carbasugar oligosaccharide cyclophellitols offer a powerful new approach for the design of robust endoglycosidase inhibitors, while the synthesis procedures presented here should allow adaptation towards activity-based endoglycosidase probes as well as configurational isosteres targeting other endoglycosidase families

Prolonged antibiotic prophylaxis after pancreatoduodenectomy: systematic review and meta-analysis

Background: Previous studies have reported conflicting results of prolonged antibiotic prophylaxis on infectious complications after pancreatoduodenectomy. This study evaluated the effect of prolonged antibiotics on surgical-site infections (SSIs) after pancreatoduodenectomy. Methods: A systematic review and meta-analysis was undertaken of SSIs in patients with perioperative (within 24 h) versus prolonged antibiotic (over 24 h) prophylaxis after pancreatoduodenectomy. SSIs were classified as organ/space infections or superficial SSI within 30 days after surgery. ORs were calculated using a Mantel–Haenszel fixed-effect model. Results: Ten studies were included in the qualitative analysis, of which 8 reporting on 1170 patients were included in the quantitative analysis. The duration of prolonged antibiotic prophylaxis varied between 2 and 10 days after surgery. Four studies reporting on 782 patients showed comparable organ/space infection rates in patients receiving perioperative and prolonged antibiotics (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, among patients with preoperative biliary drainage (5 studies reporting on 577 patients), organ/space infection rates were lower with prolonged compared with perioperative antibiotics (OR 2.09, 1.43 to 3.07). Three studies (633 patients) demonstrated comparable superficial SSI rates between patients receiving perioperative versus prolonged prophylaxis (OR 1.54, 0.97 to 2.44), as well as in patients with preoperative biliary drainage in 4 studies reporting on 431 patients (OR 1.60, 0.89 to 2.88). Conclusion: Prolonged antibiotic prophylaxis is associated with fewer organ/space infection in patients who undergo preoperative biliary drainage. However, the optimal duration of antibiotic prophylaxis after pancreatoduodenectomy remains to be determined and warrants confirmation in an RCT

Mechanism based heparanase inhibitors reduce cancer metastasis in vivo

Heparan sulfate proteoglycans (HSPGs) mediate essential interactions throughout the extracellular matrix (ECM), providing signals that regulate cellular growth and development. Altered HSPG composition during tumorigenesis strongly aids cancer progression. Heparanase (HPSE) is the principal enzyme responsible for extracellular heparan sulfate catabolism and is markedly up-regulated in aggressive cancers. HPSE overactivity degrades HSPGs within the ECM, facilitating metastatic dissemination and releasing mitogens that drive cellular proliferation. Reducing extracellular HPSE activity reduces cancer growth, but few effective inhibitors are known, and none are clinically approved. Inspired by the natural glycosidase inhibitor cyclophellitol, we developed nanomolar mechanism-based, irreversible HPSE inhibitors that are effective within physiological environments. Application of cyclophellitol-derived HPSE inhibitors reduces cancer aggression in cellulo and significantly ameliorates murine metastasis. Mechanism-based irreversible HPSE inhibition is an unexplored anticancer strategy. We demonstrate the feasibility of such compounds to control pathological HPSE-driven malignancies.NWO"Endoglycoprobe”714.018.002Bio-organic Synthesi

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

Rationale &amp; Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting &amp; Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P &lt; 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P &lt; 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P &lt; 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P &lt; 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.</p

Minimally invasive versus open distal pancreatectomy (LEOPARD): Study protocol for a randomized controlled trial

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. Methods: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. Discussion: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Trial registration: Dutch Trial Register, NTR5188. Registered on 9 April 201