Notes

Early idea associated with tumour-response to be able to radiotherapy within NSCLC patients.
Acetaminophen inhibits cell-free hemoglobin-induced lipid peroxidation and improves renal function in severe falciparum malaria but has not been evaluated in other infections with prominent hemolysis, including Plasmodium knowlesi malaria.

PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500mg or 1000mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis.

During 2016-2018, 396 patients (aged 12-96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively).

Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis.

NCT03056391.
NCT03056391.
Pulmonary function (PF) progressively declines with aging. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) are predictors of morbidity of pulmonary and cardiovascular diseases and all-cause mortality. In addition, reduced PF is associated with elevated chronic low-grade systemic inflammation, glucose metabolism, body fatness, and low muscle strength. It may suggest pleiotropic genetic effects between PF with these age-related factors.

We evaluated whether FEV1 and FVC share common pleiotropic genetic effects factors with interleukin-6, high-sensitivity C-reactive protein, body mass index, muscle (grip) strength, plasma glucose, and glycosylated hemoglobin in 3,888 individuals (age range 26-106). We employed sex-combined and sex-specific correlated meta-analyses to test whether combining genome-wide association p-values from two or more traits enhances the ability to detect variants sharing effects on these correlated traits.

We identified 32 loci for PF, including 29 ations. Integration of gene expression and genomic annotation data shows enrichment of our genetic variants in lung, blood, adipose, pancreas, and muscles, among others. Our findings highlight the critical roles of identified gene/locus in systemic inflammation, glucose metabolism, strength performance, PF, and pulmonary disease, which are involved in accelerated biological aging.
Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse.

The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM).

We analyzed data from the ongoing observational PREG study (NCT04270578).

The study was conducted at the University Hospital Tübingen.

We examined 167 women (33 with GDM) during gestational week 27 ± 2.2.

Subjects underwent 5-point OGTT with a 75-g glucose load.

We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome.

Insulin secretion was significantly lower in women with GDM (P < 0.001). Postload GLP-1 and GIP were ~20% higher in women with GDM (all P < 0.05) independent of age, body mass index, and gestational age. GLP-1 increase was associated with insulin secretion only in GDM, but not in normal glucose tolerance. Postprandial GLP-1 levels were negatively associated with birth weight.

The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.
The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.
Rhizomes are important organs allowing many clonal plants to persist and reproduce under stressful climates with longer rhizomes, indicating enhanced ability of the plants to spread vegetatively. We do not, however, know either how rhizome construction costs change with increasing length or how they vary with environmental conditions.

We analysed the rhizome length vs. mass scaling relationship, the plasticity in the scaling relationships, their genetic basis and how scaling relationships are linked to plant fitness. We used data from 275 genotypes of a clonal grass Festuca rubra originating from 11 localities and cultivated under four contrasting climates. Data were analysed using standard major axis regression, mixed-effect regression models and a structural equation model.

Rhizome construction costs increased (i.e. lower specific rhizome length) with increasing length. The trait scaling relationships were modulated by cultivation climate, and its effects also interacted with the climate of origin of the experimental plants. With increasing length, increasing moisture led to a greater increase in rhizome construction costs. Plants with lower rhizome construction costs showed significantly higher fitness.

This study suggests that rhizome scaling relationships are plastic, but also show genetic differentiation and are linked to plant fitness. Therefore, to persist under variable environments, modulation in scaling relationships could be an important plant strategy.
This study suggests that rhizome scaling relationships are plastic, but also show genetic differentiation and are linked to plant fitness. Therefore, to persist under variable environments, modulation in scaling relationships could be an important plant strategy.Effect of Nitrous Oxide and of Narcotic Premedication on the Alveolar Concentration Required for Anesthesia. By , Eger EI II. Anesthesiology 1964; 25302-6. Hyperthermia during Anesthesia. By Saidman LJ, Havard ES, Eger EI II. JAMA 1964; 1901029-32. The minimum alveolar concentration (MAC) of an inhaled anesthetic preventing movement in response to a surgical incision as a measure of equipotency was "invented" in 1964 at the University of California, San Francisco. The principal advantage of MAC is that it allows the pharmacologic effects of inhaled anesthetics to be compared against each other at a similar anesthetic depth. Thus, if the hemodynamic effect (hypotension, decreased cardiac output) of anesthetic "A" is greater than that of anesthetic "B," the anesthesiologist may elect to use "A" in patients with myocardial dysfunction. A rare side effect of a volatile anesthetic is that in some patients, malignant hyperthermia may occur with or without succinylcholine use. This phenomenon was detected in a patient in whom halothane MAC was being measured. The availability of the Severinghaus blood gas device allowed for the first ever measurement of the metabolic and respiratory acidemia that accompanies malignant hyperthermia.Nonsteroidal anti-inflammatory drugs are among the most commonly administered drugs in the perioperative period due to their prominent role in pain management. However, they potentially have perioperative consequences due to immune-modulating effects through the inhibition of prostanoid synthesis, thereby affecting the levels of various cytokines. These effects may have a direct impact on the postoperative outcome of patients since the immune system aims to restore homeostasis and plays an indispensable role in regeneration and repair. By affecting the immune response, consequences can be expected on various organ systems. This narrative review aims to highlight these potential immune system-related consequences, which include systemic inflammatory response syndrome, acute respiratory distress syndrome, immediate and persistent postoperative pain, effects on oncological and neurologic outcome, and wound, anastomotic, and bone healing.Chemotactic migration is a fundamental cellular behavior relying on the coordinated flux of lipids and cargo proteins toward the leading edge. We found here that the core autophagy protein ATG9A plays a critical role in the chemotactic migration of several human cell lines, including highly invasive glioma cells. Depletion of ATG9A protein altered the formation of large and persistent filamentous actin (F-actin)-rich lamellipodia that normally drive directional migration. Using live-cell TIRF microscopy, we demonstrated that ATG9A-positive vesicles are targeted toward the migration front of polarized cells, where their exocytosis correlates with protrusive activity. Finally, we found that ATG9A was critical for efficient delivery of β1 integrin to the leading edge and normal adhesion dynamics. Collectively, our data uncover a new function for ATG9A protein and indicate that ATG9A-positive vesicles are mobilized during chemotactic stimulation to facilitate expansion of the lamellipodium and its anchorage to the extracellular matrix.
Post-operative delirium (POD) is associated with increased morbidity and mortality rates in older patients. Neuroinflammation, the activation of the intrinsic immune system of the brain, seems to be one of the mechanisms behind the development of POD. The aim of this study was to explore the association between the perioperative inflammatory response and the development of POD in a cohort of older oncological patients in need for surgery.

In this prospective cohort study, patients 65years and older in need for oncologic surgery were included. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1β), IL-6, IL10 and Neutrophil gelatinase-associated lipocalin (NGAL) were measured in plasma samples pre- and post-operatively. Delirium Observation Screening Scale (DOS) was used as screening instrument for POD in the first week after surgery. LL37 price In case of positive screening, diagnosis of POD was assessed by a clinician.

Between 2010 and 2016, plasma samples of 311 patients with median age of 72years (range 65-89) were collected. A total of 38 (12%) patients developed POD in the first week after surgery. The perioperative increase in plasma levels of IL-10 and NGAL were associated with POD in multivariate logistic regression analysis (OR 1.33 [1.09-1.63] P = 0.005 and OR 1.30 [1.03-1.64], P = 0.026, respectively). The biomarkers CRP, IL-1β and IL-6 were not significantly associated with POD.

Increased surgery-evoked inflammatory responses of IL-10 and NGAL are associated with the development of POD in older oncological patients. The outcomes of this study contribute to understanding the aetiology of neuroinflammation and the development of POD.
Increased surgery-evoked inflammatory responses of IL-10 and NGAL are associated with the development of POD in older oncological patients. The outcomes of this study contribute to understanding the aetiology of neuroinflammation and the development of POD.
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