Cobbpridgen7249

Finally, we demonstrated increased autophagic death in KLF4-expressing cells in response to glucose starvation. Collectively, these results relate KLF4 to non-Warburg metabolic behaviors that support its role as a tumor suppressor and could make KLF4 a target for new cancer treatments.Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.Cacopsylla pyri (L.) (Hemiptera Psyllidae) is a key pest of pear orchards in Spain. The large number of insecticide treatments necessary for control may be an important contributor to the emergence of resistance. Laboratory toxicity and biochemical assays are necessary to validate the existence of insecticide resistance and establish the underlying mechanisms. All the methodologies developed to evaluate enzyme activity in C. pyri to date have incorporated "pools" of adults to detect minimum activity ranges. In this study, we determined the optimal working conditions for evaluation of the activities of esterase, glutathione S-transferase and NADPH-cytochrome P450 reductase in individual insects via colorimetric methods using a microplate reader. The main factors affecting enzymatic analysis activity, such as enzyme source and substrate concentration, filter wavelength, buffer pH, reaction time and additives, were evaluated for optimization. Determining the frequency of resistant individuals within a population could be used as an indicator for the evolution of insecticide resistance over time. Two laboratory strains, one of them selected with cypermethrin, and two field populations were analyzed for this purpose. The data obtained revealed high values and great variation in the activity ranges of esterase (EST) in the insecticide-selected population as well as in the field populations validating the applied methodology.The scope of this paper is the design of an interval observer bundle for the guaranteed state estimation of an uncertain induction machine with linear, time-varying dynamics. These guarantees are of particular interest in the case of safety-critical systems. In many cases, interval observers provide large intervals for which the usability becomes impractical. Hence, based on a reduced-order hybrid interval observer structure, the guaranteed enclosure within intervals of the magnetizing current's estimates is improved using a bundle of interval observers. One advantage of such an interval observer bundle is the possibility to reinitialize the interval observers at specified timesteps during runtime with smaller initial intervals, based on previously observed system states, resulting in decreasing interval widths. Thus, unstable observer dynamics are considered so as to take advantage of their transient behavior, whereby the overall stability of the interval estimation is maintained. An algorithm is presented to determine the parametrization of reduced-order interval observers. To this, an adaptive observer gain is introduced with which the system states are observed optimally by considering a minimal interval width at variable operating points. Furthermore, real-time capability and validation of the proposed methods are shown. The results are discussed with simulations as well as experimental data obtained with a test bench.Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. see more The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50-0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67-0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.Myosteatosis is a complex condition, associated with aging and diverse pathological conditions (e.g., diabetes), that contributes to mobility disability. Improved characterization of myosteatosis is required to develop targeted interventions to maintain muscle health in aging. We first determined the associations between plasma metabolites and intermuscular fat (IMF) in a cross-sectional analysis of 313 older Black men from Health ABC Study. Using partial correlation analysis, 34/350 metabolites were associated with IMF, the majority of which were lipids and organic acids. Next, we used Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), as an indicator of metabolic health to delineate the anthropometric, functional, and metabolic heterogeneity of myosteatosis in a case-control matching analysis. We categorized participants based on their IMF and HOMA-IR levels into Low-IMF with Low- versus High-HOMA, as well as High-IMF with Low- versus High-HOMA. Among participants with similar levels of IMF, those who were metabolically unhealthy, i.e., with High HOMA-IR, had higher fat and lean mass, muscle strength, and had hyperglycemia, hypertriglyceridemia, hyperinsulinemia, and higher levels of plasma metabolites belonging to diacylglycerols, triacylglycerols, fatty acid and aminoacyl-tRNA biosynthesis pathways versus those with Low HOMA-IR. In summary, HOMA-IR delineates the heterogeneity of myosteatosis by distinguishing metabolically healthy versus unhealthy individuals.Solid boosters are an emerging concept for improving the performance and especially the energy storage density of the redox flow batteries, but thermodynamical and practical considerations of these systems are missing, scarce or scattered in the literature. In this paper we will formulate how these systems work from the point of view of thermodynamics. We describe possible pathways for charge transfer, estimate the overpotentials required for these reactions in realistic conditions, and illustrate the range of energy storage densities achievable considering different redox electrolyte concentrations, solid volume fractions and solid charge storage densities. Approximately 80% of charge storage capacity of the solid can be accessed if redox electrolyte and redox solid have matching redox potentials. 100 times higher active areas are required from the solid boosters in the tank to reach overpotentials of less then 10 mV.Despite advances in the development and introduction of vaccines against the major bacterial causes of meningitis, the disease and its long-term after-effects remain a problem globally. The Global Roadmap to Defeat Meningitis by 2030 aims to accelerate progress through visionary and strategic goals that place a major emphasis on preventing meningitis via vaccination. Global vaccination against Haemophilus influenzae type B (Hib) is the most advanced, such that successful and low-cost combination vaccines incorporating Hib are broadly available. More affordable pneumococcal conjugate vaccines are becoming increasingly available, although countries ineligible for donor support still face access challenges and global serotype coverage is incomplete with existing licensed vaccines. Meningococcal disease control in Africa has progressed with the successful deployment of a low-cost serogroup A conjugate vaccine, but other serogroups still cause outbreaks in regions of the world where broadly protective and affordable vaccines have not been introduced into routine immunization programs. Progress has lagged for prevention of neonatal meningitis and although maternal vaccination against the leading cause, group B streptococcus (GBS), has progressed into clinical trials, no GBS vaccine has thus far reached Phase 3 evaluation. This article examines current and future efforts to control meningitis through vaccination.Although coagulation disorders and immune/inflammatory response have been associated with the final outcome of patients with sepsis, their link with thetemporaryclinical deterioration or improvement of patients is unknown. We aimed to investigate this link. We prospectively included consecutive patients admitted to the intensive care unit (ICU) with a suspected diagnosis of infection and evaluated within the first 24 h from admission. Blood levels of many cytokines and inflammatory and coagulation factors were measured and their predictive value was assessed by calculating the Area Under the Receiver Operating Characteristic (AUROC) curves. Patients (n = 102) were allocated in five groups, i.e., sepsis (n = 14), severe sepsis (n = 17), septic shock (n = 28), Systemic Inflammatory Response Syndrome (SIRS) without infection (n = 17), and trauma/surgery without SIRS or infection (n = 26). In septic shock, coagulation factors FVII and FIX and Protein C had AUROCs 0.67-0.78. In severe sepsis, Antithrombin III, Protein C, C-reactive protein, Procalcitonin and Thrombopoietin had AUROCs 0.