• Energy Research
• 3. Good health close
• 1. No poverty close
• DE close
• RU close

Concentrations of carotenoids, retinoids and tocopherols were determined in the homogenate of macroscopically normal appearing oropharyngeal mucosa from 10 chronic alcoholics and from 11 control patients. All the alcoholics except one had oropharyngeal cancer. No significant difference was found in tissue levels of carotenoids and tocopherols between alcoholics and controls. Furthermore, in seven of 11 controls, retinol was undetectable in the oropharyngeal mucosa, while in the alcoholics only two out of 10 had unmeasurable retinol levels. These results do not support the concept that ethanol-associated oropharyngeal carcinogenesis is due, at least in part, to local deficiencies in retinoids, carotenoids or alpha-tocopherols.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, antagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including intersection points to the new generation of antidiabetic drugs. We provide insight into the effectiveness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Large uncertainties still dominate the hypothesis of an abrupt large-scale shift of the Amazon forest caused by climate change [Amazonian forest dieback (AFD)] even though observational evidence shows the forest and regional climate changing. Here, we assess whether mitigation or adaptation action should be taken now, later, or not at all in light of such uncertainties. No action/later action would result in major social impacts that may influence migration to large Amazonian cities through a causal chain of climate change and forest degradation leading to lower river-water levels that affect transportation, food security, and health. Net-present value socioeconomic damage over a 30-year period after AFD is estimated between US dollar (USD) $957 billion (×10 9 ) and $3,589 billion (compared with Gross Brazilian Amazon Product of USD $150 billion per year), arising primarily from changes in the provision of ecosystem services. Costs of acting now would be one to two orders of magnitude lower than economic damages. However, while AFD mitigation alternatives—e.g., curbing deforestation—are attainable (USD $64 billion), their efficacy in achieving a forest resilience that prevents AFD is uncertain. Concurrently, a proposed set of 20 adaptation measures is also attainable (USD $122 billion) and could bring benefits even if AFD never occurs. An interdisciplinary research agenda to fill lingering knowledge gaps and constrain the risk of AFD should focus on developing sound experimental and modeling evidence regarding its likelihood, integrated with socioeconomic assessments to anticipate its impacts and evaluate the feasibility and efficacy of mitigation/adaptation options.

Patients with alcoholic liver disease frequently exhibit iron overload in association with increased hepatic fibrosis. Even moderate alcohol consumption elevates body iron stores; however, the underlying molecular mechanisms are unknown. Hepcidin, a circulatory peptide synthesized in the liver, is a key mediator of iron metabolism. Ethanol metabolism significantly down-regulated both in vitro and in vivo hepcidin mRNA and protein expression. 4-Methylpyrazole, a specific inhibitor of the alcohol-metabolizing enzymes, abolished the effects of ethanol on hepcidin. However, ethanol did not alter the expression of transferrin receptor1 and ferritin or the activation of iron regulatory RNA-binding proteins, IRP1 and IRP2. Mice maintained on 10-20% ethanol for 7 days displayed down-regulation of liver hepcidin expression without changes in liver triglycerides or histology. This was accompanied by elevated duodenal divalent metal transporter1 and ferroportin protein expression. Injection of hepcidin peptide negated the effect of ethanol on duodenal iron transporters. Ethanol down-regulated hepcidin promoter activity and the DNA binding activity of CCAAT/enhancer-binding protein alpha (C/EBPalpha) but not beta. Interestingly, the antioxidants vitamin E and N-acetylcysteine abolished both the alcohol-mediated down-regulation of C/EBPalpha binding activity and hepcidin expression in the liver and the up-regulation of duodenal divalent metal transporter 1. Collectively, these findings indicate that alcohol metabolism-mediated oxidative stress regulates hepcidin transcription via C/EBPalpha, which in turn leads to increased duodenal iron transport.

Purpose: The study tests conventional and behavioral pricing multifactor impact on price fragility from the equity market of Pakistan.Methodology: The positivist approach is used to deduct study rationale via probability sampling. At the same time, systematic sampling for data collection of PSX is tested in parallel to mean-variance random walk theory.Findings: The impact of conventional factors is significant on price fragility in the short run and vice versa in the long run. Specifically, herd behavior and disposition effects are found to be insignificant. But size, value, illiquidity, and price earning had a significant impact on price fragility in the short run.Limitations: The current research has not covered the desired scope of the topic due to time limitations, lack of harmony in corporate data on databases, and literature on price fragility being very scarce.Implication: In PSX, there is a need to develop a corporate culture to promote the standard modern financial practice to enhance financial productivity and sustainability. For corporate culture to be established, corporate governance boards should be established, and family governance systems should be replaced by an independent democratic board. Mispricing and arbitragers need serious control.Originality: The value of the research is that little research currently exists on about pricing multifactor impact on price fragility.

Abstract The clinical implementation of a variable relative biological effectiveness (RBE) in proton therapy is currently controversially discussed. Initial clinical evidence indicates a variable proton RBE, which needs to be verified. In this study, a radiation response modelling framework for assessing clinical RBE variability is established. It was applied to four selected glioma patients (grade III) treated with adjuvant radio(chemo)therapy and who developed late morphological image changes on T1-weighted contrast-enhanced (T1w-CE) magnetic resonance (MR) images within approximately two years of recurrence-free follow-up. The image changes were correlated voxelwise with dose and linear energy transfer (LET) values using univariable and multivariable logistic regression analysis. The regression models were evaluated by the area-under-the-curve (AUC) method performing a leave-one-out cross validation. The tolerance dose TD50 at which 50% of patient voxels experienced toxicity was interpolated from the models. A Monte Carlo (MC) model was developed to simulate dose and LET distributions, which includes variance reduction (VR) techniques to decrease computation time. Its reliability and accuracy were evaluated based on dose calculations of the clinical treatment planning system (TPS) as well as absolute dose measurements performed in the patient specific quality assurance. Morphological image changes were related to a combination of dose and LET. The multivariable models revealed cross-validated AUC values of up to 0.88. The interpolated TD50 curves decreased with increasing LET indicating an increase in biological effectiveness. The MC model reliably predicted average TPS dose within the clinical target volume as well as absolute water phantom dose measurements within 2% accuracy using dedicated VR settings. The observed correlation of dose and LET with late brain tissue damage suggests considering RBE variability for predicting chronic radiation-induced brain toxicities. The MC model simulates radiation fields in patients precisely and time-efficiently. Hence, this study encourages and enables in-depth patient evaluation to assess the variability of clinical proton RBE.

We investigated induction of chromosome aberrations (CA) in human lymphocytes when exposed to 150 MeV and spread out Bragg peak (SOBP) proton beams, and 199 MeV/u carbon beam which are currently widely used for cancer treatment and simultaneously are important components of cosmic radiation. For a comparison, the boron ions of much lower energy 22 MeV/u and a 60Co γ rays were used. Dose-effect curves as well as the distributions of CA were studied using Poisson and Neyman type A statistics. Systematics of experimentally determined parameters, their dependence on applied doses and irradiation quality are presented.