The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer.

Background: Systemic inflammation is associated with reduced quality of life and increased symptoms in patients with advanced cancer. The aims of this study were to examine the relationships between inflammatory biomarkers and the Patient Reported Outcome Measures (PROMs) of pain, appetite and fatigue; and to explore whether levels of baseline biomarkers were associated with changes in these PROMs following treatment with corticosteroids. Material and methods: An exploratory analysis was done on a trial examining the analgesic properties of corticosteroids in patients with advanced cancer. Inclusion criteria were: >18 years, taking opioids for moderate or severe cancer pain; pain ≥4 (numerical rating scale 0–10). Serum was extracted and levels of inflammatory biomarkers were assessed. PROMs of pain, appetite and fatigue were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30). The relationships between PROMs and inflammatory biomarkers were examined using Spearman Rho-Rank and multiple regression analysis. Results: Data were available on 49 patients. Levels of sTNF-r1, IL-6, IL-18, MIF, MCP-1, TGF-β1, IL-1ra, and C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) were elevated; IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12(p70), interferon-γ, MIP-1α, and TNF-α were below the level of detection. The following correlations were observed: appetite and IL-6 and CRP; fatigue and IL-1ra (rs: 0.38–0.41, p< .01). There was no association between pretreatment biomarkers and effect from corticosteroid treatment. Conclusion: In patients with advanced cancer and pain, some pro-inflammatory cytokines were related to appetite and fatigue. Inflammatory biomarkers were not associated with pain or with the efficacy of corticosteroid therapy. Further research examining the attenuation of the systemic inflammatory response and possible effects on symptoms would be of interest

Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output.

Neural organoids have the potential to improve our understanding of human brain development and neurological disorders. However, it remains to be seen whether these tissues can model circuit formation with functional neuronal output. Here we have adapted air-liquid interface culture to cerebral organoids, leading to improved neuronal survival and axon outgrowth. The resulting thick axon tracts display various morphologies, including long-range projection within and away from the organoid, growth-cone turning, and decussation. Single-cell RNA sequencing reveals various cortical neuronal identities, and retrograde tracing demonstrates tract morphologies that match proper molecular identities. These cultures exhibit active neuronal networks, and subcortical projecting tracts can innervate mouse spinal cord explants and evoke contractions of adjacent muscle in a manner dependent on intact organoid-derived innervating tracts. Overall, these results reveal a remarkable self-organization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and disease

Evaluation of MLH1 variants of unclear significance

Inactivating mutations in the MLH1 gene cause the cancer predisposition Lynch syndrome, but for small coding genetic variants it is mostly unclear if they are inactivating or not. Nine such MLH1 variants have been identified in South American colorectal cancer (CRC) patients (p.Tyr97Asp, p.His112Gln, p.Pro141Ala, p.Arg265Pro, p.Asn338Ser, p.Ile501del, p.Arg575Lys, p.Lys618del, p.Leu676Pro), and evidence of pathogenicity or neutrality was not available for the majority of these variants. We therefore performed biochemical laboratory testing of the variant proteins and compared the results to protein in silico predictions on structure and conservation. Additionally, we collected all available clinical information of the families to come to a conclusion concerning their pathogenic potential and facilitate clinical diagnosis in the affected families. We provide evidence that four of the alterations are causative for Lynch syndrome, four are likely neutral and one shows compromised activity which can currently not be classified with respect to its pathogenic potential. The work demonstrates that biochemical testing, corroborated by congruent evolutionary and structural information, can serve to reliably classify uncertain variants when other data are insufficient.Barretos Cancer Hospital was partially funded by FINEP‐CT‐INFRA, Grant Number: 02/2010, Radium Hospital Foundation (Oslo, Norway), Helse Sør‐Øst (Norway); Deutsche Forschungsgemeinschaft, Grant Number: PL688/2‐1info:eu-repo/semantics/publishedVersio

Personal determinants of change agents’ decision-making behavior in community health promotion: a qualitative study

Abstract Background Implementing environmental changes to promote healthier communities requires initial positive decisions by change agents from local politics and government. However, there is little research on what influences the change agents' decisions. This explorative, qualitative study aims to identify the personal determinants of the decision-making behavior of local change agents. Methods We conducted semi-structured interviews to assess the personal determinants of decision-making behavior among 22 change agents from local politics and government. Relevant determinants were identified through a structured content analysis of the interview transcripts using the software MAXQDA 2020. Results We found the following seven essential clusters of personal determinants of the decision-making behavior of change agents from local politics and government: Imprinting, socialization, and biography; experiences and involvement; attitudes and outcome expectations towards important issues and aspects; knowledge; emotions; personal benefits; and the perceived influences of others. Conclusions The identified personal determinants might serve as a source of understanding the decision-making behavior of change agents in community decision-making processes. Our findings can contribute to the effective planning and implementation of evidence-based multilevel interventions related to changing environmental conditions in communities and provide important information on which personal determinants should be considered when derive strategies for community health promotion within a systematic approach of developing an intervention program theory

Risk-Benefit Assessment of an Increase in the Iodine Fortification Level of Foods in Denmark-A Pilot Study

Iodine deficiency is one of the most common nutritional disorders worldwide. In Denmark, the mandatory iodine fortification of salt of 13 ppm was introduced in 2000 to eradicate mild to moderate iodine deficiency and the fortification level was increased to 20 ppm in 2019. However, the optimal iodine intake is a narrow interval, and the risk of disease increases with intakes both below and above this interval. In this study, we quantified the risk–benefit balance in the Danish adult population by increasing the mandatory fortification level. We applied a risk–benefit assessment approach in which population-level iodine intakes before and after the increase in fortification were integrated with epidemiological evidence of the association between iodine nutrition status and risk of relevant diseases to estimate the number of cases caused or prevented and estimated health impact in terms of disability-adjusted life years (DALY). We estimated an overall beneficial health impact and prevention of 34.9 (95% UI: −51.6; −21.7) DALY per 100,000 adults in the population annually with the increase in fortification level. Prevention of low IQ in children due to maternal iodine deficiency was the primary contributor to overall health gain. The gain in healthy life years comes at the expense of extra cases of goiter due to iodine excess. Due to lack of data, hypo- and hyperthyroidism related to iodine status were not included. Neither were children as a population group. Because of this, as well as uncertainties inherent in the model and data used, results should be interpreted with caution. We argue that nation-specific, quantitative assessments of the public health impact of fortification programs provide transparent, evidence-based decision support. Future research should aim to enable the inclusion of all relevant health effects as well as children in the assessment

Correlations between the analysed cytokines.

<p>Correlations between the analysed cytokines.</p

Biomarkers and observed serum concentrations.

<p>Biomarkers and observed serum concentrations.</p

EORTC QLQ-C30 measurements at baseline and correlations with cytokine serum concentrations.

<p>EORTC QLQ-C30 measurements at baseline and correlations with cytokine serum concentrations.</p