The RNA world scenario posits replication by RNA polymerases. On early Earth, a geophysical setting is required to separate hybridized strands after their replication and to localize them against ...diffusion. We present a pointed heat source that drives exponential, RNA-catalyzed amplification of short RNA with high efficiency in a confined chamber. While shorter strands were periodically melted by laminar convection, the temperature gradient caused aggregated polymerase molecules to accumulate, protecting them from degradation in hot regions of the chamber. These findings demonstrate a size-selective pathway for autonomous RNA-based replication in natural nonequilibrium conditions.
Proton gradients are essential for biological systems. They not only drive the synthesis of ATP, but initiate molecule degradation and recycling inside lysosomes. However, the high mobility and ...permeability of protons through membranes make pH gradients very hard to sustain in vitro. Here we report that heat flow across a water-filled chamber forms and sustains stable pH gradients. Charged molecules accumulate by convection and thermophoresis better than uncharged species. In a dissociation reaction, this imbalances the reaction equilibrium and creates a difference in pH. In solutions of amino acids, phosphate, or nucleotides, we achieve pH differences of up to 2 pH units. The same mechanism cycles biomolecules by convection in the created proton gradient. This implements a feedback between biomolecules and a cyclic variation of the pH. The finding provides a mechanism to create a self-sustained proton gradient to drive biochemical reactions.
We assessed the therapeutic contribution of the individual components of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) agonists alone and in combination upon energy ...homeostasis and glycemic control in diet-induced obese, diabetic nonhuman primates. The pharmacological active dose ranges of selective agonists were established through a dose-finding study, followed by a 6-week chronic study. Repeated subcutaneous administration of a selective GCGR agonist (30 µg/kg once daily) did not affect food intake or body weight, whereas the selective GLP-1R agonist (3 µg/kg once daily) alone decreased energy intake by 18% and body weight by 3.8% ± 0.9%. Combination of both agonists reduced significantly cumulative food intake by 27% and body weight by 6.6% ± 0.9%. Fasting plasma glucose (FPG) was improved by GLP-1R agonist (baseline vs end of study, 176.7 ± 34.0 vs 115.9 ± 16.1 mg/dL). In contrast, groups exposed to GCGR agonist experienced nonsignificant elevations of FPG. More accurate assessment of therapeutic interventions on glucose homeostasis was tested by an IV glucose tolerance test. Glucose excursion was significantly elevated by chronic GCGR agonist administration, whereas it was significantly decreased in GLP-1R agonist-treated monkeys. In the combination group, a nonsignificant increase of glucose excursion was seen, concomitantly with significantly increased insulin secretion. We conclude that chronic glucagon agonism does not affect energy homeostasis in nonhuman primates. In combination with GLP-1R agonism, glucagon agonism synergistically enhances negative energy balance with resulting larger body weight loss. However, adding GCGR to GLP-1R agonism diminishes glycemic control in diabetic monkeys. Therefore, long-term therapeutic implications of using GLP-1R/GCGR coagonists for weight management in diabetes warrants further scrutiny.
Summary
Expectations, real or false, affect the way patients respond to their illnesses. We assessed therapy-related expectations in relation to global quality of life in 55 cancer patients before ...and after radiotherapy.
Factor analysis indicated that therapy-related expectations come into three broad categories—pain/emotional control, healing and tumour/symptom control. 35 patients expected ‘healing’ even though curative treatment was intended in only 19 and all patients had been fully informed. The expectation of healing was associated with high quality of life, and the same was true of perception of healing after radiotherapy. In the group as a whole, quality of life was little altered by radiotherapy, but it became substantially worse in those patients who had expected healing but perceived that this had failed, even though physician-assessed Karnofsky status did not change.
These findings indicate that the expectation of healing, in cancer patients, is a component of a good global quality of life, whereas more limited expectations (pain control, tumour control) relate to lower quality of life. Patients’ expectations deserve further study as a novel approach to improving care.
Evaluation of the effects of radiotherapy with respect to following dependants variables: patients’ quality of life, patients’ expectation toward the therapy and their subjective evaluation of ...treatment effects, physicians’ expectation toward the therapy and their evaluation of the effects.
(1) Does the therapeutic concept help to improve the patients’ quality of life? (2) Does the radiotherapy achieve the patients’ expectations concerning the therapy? (3) Does the radiotherapy achieve the physicians’ therapeutical aims after the patients’ treatment in hospital and at a later presentation?
Prospective observational study with repeated measurement. Three points of measurement: at admission to hospital, at the end of inpatient therapy and at outpatient follow-up.
42 patients with cancer of various sites. All variables were assessed by means of questionnaires: EORTC QLQ C-30, PLC (Siegrist), patient expectancy and satisfaction scales, physician expectancy and satisfaction scales.
Data analyses will focus on MANOVAS and on calculating of correlations and differences regarding patients’ and physicians’ ratings. The study has just been completed and data analysis is underway.
The present study investigates patients' expectations toward radiotherapy and their associations to quality of life and physician judgements. Fifty-five patients with tumors of different sites (30 ...with previous tumor-related surgery, 25 without surgery) admitted to the department of radiotherapy filled out a standardized questionnaire (EORTC QLQ-C30, PLC by Siegrist et al., therapy-related expectations and success) before and after inpatient radiotherapy. The corresponding physician ratings were collected. Fifty-eight percent of the patients expected the therapeutic goal "healing", whereas from the physician's standpoint this was realistic in only 7% of cases. The specific radiotherapy-related expectations "tumor control" and "pain relief" reached almost the same levels in patients and physician (71% vs 71% and 40% vs 44%). Patients with healing expectancy reported higher quality of life at the beginning of the therapy (53.4% vs 39.9%); patients expecting pain relief reported lower quality of life (37.1% vs 54.5%). Surgical patients who had been operated on within the past year (n = 18) showed a particularly high healing expectancy (83%), whereas patients whose operation dated back more than 1 year focused on pain relief as therapeutic goal (83%). The surgeon, as the primary contact person for patients, can influence patients' therapy-related expectations. In explaining the overall therapeutic strategy, surgeons should also mention the scope and limits of adjuvant therapies.
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