Medicine’s collision with false hope: The False Hope Harms (FHH) argument

The goal of this paper is to introduce the false hope harms (FHH) argument, as a new concept in healthcare. The FHH argument embodies a conglomerate of specific harms that have not convinced providers to stop endorsing false hope. In this paper, it is submitted that the healthcare profession has an obligation to avoid collaborating or participating in, propagating or augmenting false hope in medicine. Although hope serves important functions—it can be ‘therapeutic’ and important for patients’ ‘self-identity as active agents’— the presentation of false hope along the hope continuum entails a misconstrued balancing act. By not speaking up against unrealistic patient and family requests—including some requests for rights to try, resuscitative efforts in terminally ill patients, or other demands for non-beneficial treatments—healthcare providers precipitate harms, i.e., the FHH. These harms arise on both individual and communal levels and cannot be ignored. The goal of this paper is not to offer a definition of false hope, because the phenomenon of false hope is too complex for any simple definition. Instead, this paper seeks to make four points while outlining the FHH argument: consumer medicine and false hope are connected; providers and patients are very vulnerable in the system of consumer medicine; providers have a responsibility to stand up against false hope; and how the FHH argument could perhaps offer a footing to resist giving in to false hope.     

Temperature Affects the Use of Storage Fatty Acids as Energy Source in a Benthic Copepod (Platychelipus littoralis,Harpacticoida)

The utilization of storage lipids and their associated fatty acids (FA) is an important means for organisms to cope with periods of food shortage, however, little is known about the dynamics and FA mobilization in benthic copepods (order Harpacticoida). Furthermore, lipid depletion and FA mobilization may depend on the ambient temperature. Therefore, we subjected the temperate copepod Platychelipus littoralis to several intervals (3, 6 and 14 days) of food deprivation, under two temperatures in the range of the normal habitat temperature (4, 15°C) and under an elevated temperature (24°C), and studied the changes in FA composition of storage and membrane lipids. Although bulk depletion of storage FA occurred after a few days of food deprivation under 4°C and 15°C, copepod survival remained high during the experiment, suggesting the catabolization of other energy sources. Ambient temperature affected both the degree of FA depletion and the FA mobilization. In particular, storage FA were more exhausted and FA mobilization was more selective under 15°C compared with 4°C. In contrast, depletion of storage FA was limited under an elevated temperature, potentially due to a switch to partial anaerobiosis. Food deprivation induced selective DHA retention in the copepod’s membrane, under all temperatures. However, prolonged exposure to heat and nutritional stress eventually depleted DHA in the membranes, and potentially induced high copepod mortality. Storage lipids clearly played an important role in the short-term response of the copepod P. littoralis to food deprivation. However, under elevated temperature, the use of storage FA as an energy source is compromised.     

Flavonoid Intake in European Adults (18 to 64 Years)

BackgroundFlavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations.ObjectiveThe objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union.DesignWe use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids.ResultsMean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d).ConclusionsThe habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.     

Peroxisome proliferation in Hansenula polymorpha requires Dnm1p which mediates fission but not de novo formation

We show that the dynamin-like proteins Dnm1p and Vps1p are not required for re-introduction of peroxisomes in Hansenula polymorpha pex3 cells upon complementation with PEX3-GFP. Instead, Dnm1p, but not Vps1p, plays a crucial role in organelle proliferation via fission. In H. polymorpha DNM1 deletion cells (dnm1) a single peroxisome is present that forms long extensions, which protrude into developing buds and divide during cytokinesis. Budding pex11.dnm1 double deletion cells lack these peroxisomal extensions, suggesting that the peroxisomal membrane protein Pex11p is required for their formation. Life cell imaging revealed that fluorescent Dnm1p-GFP spots fluctuate between peroxisomes and mitochondria. On the other hand Pex11p is present over the entire organelle surface, but concentrates during fission at the basis of the organelle extension in dnm1 cells.Our data indicate that peroxisome fission is the major pathway for peroxisome multiplication in H. polymorpha.     

Genetic Variation in the Leptin Receptor Gene,Leptin, and Weight Gain in Young Dutch Adults

Objective: To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. Research Methods and Procedures: From two large prospective cohorts in The Netherlands (n = 17, 500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range ?2.6 to 3.1 kg) after a mean follow‐up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined. Results: Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log_e‐transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation. Discussion: Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.     

The involvement of human ribonucleases H1 and H2 in the variation of response of cells to antisense phosphorothioate oligonucleotides.

We have analyzed the response of a number of human cell lines to treatment with antisense oligodeoxynucleotides (ODNs) directed against RNA polymerase II, replication protein A, and Ha-ras. ODN-delivery to the cells was liposome-mediated or via electroporation, which resulted in different intracellular locations of the ODNs. The ODN-mediated target mRNA reduction varied considerably between the cell lines. In view of the essential role of RNase H activity in this response, RNase H was analyzed. The mRNA levels of RNase H1 and RNase H2 varied considerably in the cell lines examined in this study. The intracellular localization of the enzymes, assayed by green-fluorescent protein fusions, showed that RNase H1 was present throughout the whole cell for all cell types analyzed, whereas RNase H2 was restricted to the nucleus in all cells except the prostate cancer line 15PC3 that expressed the protein throughout the cell. Whole cell extracts of the cell lines yielded similar RNase H cleavage activity in an in vitro liquid assay, in contrast to the efficacy of the ODNs in vivo. Overexpression of RNase H2 did not affect the response to ODNs in vivo. Our data imply that in vivo RNase H activity is not only due to the activity assayed in vitro, but also to an intrinsic property of the cells. RNase H1 is not likely to be a major player in the antisense ODN-mediated degradation of target mRNAs. RNase H2 is involved in the activity assayed in vitro. The presence of cell-type specific factors affecting the activity and localization of RNase H2 is strongly suggested.     

Horizontal and vertical distribution of meiofauna on sandy beaches of the North Sea (The Netherlands, Belgium, France)

Sandy intertidal zones were analysed for the presence of meiofauna. The material was collected on six macro-tidal sandy beaches along the North Sea (The Netherlands, France, Belgium), in order to analyse the vertical and horizontal meiofaunal distribution patterns. Eleven higher meiofauna taxa (one represented by larval stage—Copepoda nauplii) were recorded. The maximum total meiofauna abundance was observed on the Dutch beach (4,295±911 ind. 10 cm⁻²) in the Westerschelde estuary, while the lowest values (361±128 ind. 10 cm⁻²) were recorded in France at the Audresselles beach. Meiofauna of the different localities consisted mainly of nematodes, harpacticoids and turbellarians. Nematodes numerically dominated all sampled stations, comprising more than 45% of the total meiofauna density. Meiofauna was mainly concentrated at the sand surface with about 70% present in the uppermost 5 cm. Meiofauna occurred across the entire intertidal zone. A clear zonation pattern in the distribution of meiofauna taxa across the beaches was observed. The present work suggests that designation of exposed sandy beaches as physically controlled (McLachlan 1988) does not explain their biological variability.     

Radial oxygen loss, a plastic property of dune slack plant species

Mean and environmentally induced differences in radial oxygen loss (ROL) were investigated for three pioneer species (i.e. Schoenus nigricans L., Juncus articulatus L. and Samolus valerandi L.) and two late-successional dune slack species (i.e. Calamagrostis epigejos L. and Carex flacca Schreber). These species were grown in a factorial design at conditions differing in moisture, light, nutrient availability and Fe²⁺ and Mn²⁺ concentrations. On average, ROL was twice as low for late-successional species compared to pioneer species, but it increased on average by a factor 1.5 for these species upon flooding while ROL was unaffected by flooding in pioneer species. Other effects of treatments on pioneer and late-successional species groups were insignificant. Species-specific plasticity in ROL was stronger than that of the species groups and varied highly with the different combinations of – interactions between – environmental cultivation conditions flooding, concentrations of Fe²⁺ and Mn²⁺, nutrient and light levels, but was not affected by differences in relative growth rates. Moreover, ROL activity was almost 20×, and significantly, higher for seedlings than for adults of Schoenus nigricans. This implies that ROL of a species depends on the stage of the life cycle and on growth conditions, something that should be considered when determining ROL. ROL activity of most species increased at (a combination of) high nutrient and at low light levels: ROL activity was strongly negatively correlated to the root/shoot ratio, which was presumably caused by a higher gas transport capacity compared to root oxygen consumption at low root/shoot ratios. The plasticity in ROL leads to a highly dynamic rhizosphere in which the oxygen influx is a function of plant species and particularly of the interactions between plant species and environmental conditions.