Aging of Non-Visual Spectral Sensitivity to Light in Humans: Compensatory Mechanisms?

The deterioration of sleep in the older population is a prevalent feature that contributes to a decrease in quality of life. Inappropriate entrainment of the circadian clock by light is considered to contribute to the alteration of sleep structure and circadian rhythms in the elderly. The present study investigates the effects of aging on non-visual spectral sensitivity to light and tests the hypothesis that circadian disturbances are related to a decreased light transmittance. In a within-subject design, eight aged and five young subjects were exposed at night to 60 minute monochromatic light stimulations at 9 different wavelengths (420–620 nm). Individual sensitivity spectra were derived from measures of melatonin suppression. Lens density was assessed using a validated psychophysical technique. Although lens transmittance was decreased for short wavelength light in the older participants, melatonin suppression was not reduced. Peak of non-visual sensitivity was, however, shifted to longer wavelengths in the aged participants (494 nm) compared to young (484 nm). Our results indicate that increased lens filtering does not necessarily lead to a decreased non-visual sensitivity to light. The lack of age-related decrease in non-visual sensitivity to light may involve as yet undefined adaptive mechanisms.     

Unveiling the Biodiversity of Deep-Sea Nematodes through Metabarcoding: Are We Ready to Bypass the Classical Taxonomy?

Nematodes inhabiting benthic deep-sea ecosystems account for >90% of the total metazoan abundances and they have been hypothesised to be hyper-diverse, but their biodiversity is still largely unknown. Metabarcoding could facilitate the census of biodiversity, especially for those tiny metazoans for which morphological identification is difficult. We compared, for the first time, different DNA extraction procedures based on the use of two commercial kits and a previously published laboratory protocol and tested their suitability for sequencing analyses of 18S rDNA of marine nematodes. We also investigated the reliability of Roche 454 sequencing analyses for assessing the biodiversity of deep-sea nematode assemblages previously morphologically identified. Finally, intra-genomic variation in 18S rRNA gene repeats was investigated by Illumina MiSeq in different deep-sea nematode morphospecies to assess the influence of polymorphisms on nematode biodiversity estimates. Our results indicate that the two commercial kits should be preferred for the molecular analysis of biodiversity of deep-sea nematodes since they consistently provide amplifiable DNA suitable for sequencing. We report that the morphological identification of deep-sea nematodes matches the results obtained by metabarcoding analysis only at the order-family level and that a large portion of Operational Clustered Taxonomic Units (OCTUs) was not assigned. We also show that independently from the cut-off criteria and bioinformatic pipelines used, the number of OCTUs largely exceeds the number of individuals and that 18S rRNA gene of different morpho-species of nematodes displayed intra-genomic polymorphisms. Our results indicate that metabarcoding is an important tool to explore the diversity of deep-sea nematodes, but still fails in identifying most of the species due to limited number of sequences deposited in the public databases, and in providing quantitative data on the species encountered. These aspects should be carefully taken into account before using metabarcoding in quantitative ecological research and monitoring programmes of marine biodiversity.     

3D-Printed Drugs for Children—Are We Ready Yet?

The first medicine manufactured by three-dimensional (3D) printing was recently approved by the Food and Drug Administration (FDA). The advantages of printing as a manufacturing route enabling more flexibility regarding the dose, and enlarging individual treatment options, have been demonstrated. There is a particular need for flexible drug delivery solutions when it comes to children. Printing as a new pharmaceutical manufacturing technology brings manufacturing closer to the patient and can easily be adjusted to the required dosing scheme, offering more flexibility for treatments. Printing of medicine may therefore become the manufacturing route of choice to provide tailored and potentially on-demand treatments for patients with individual needs. This paper intends to summarize and discuss the state of the art, the crucial aspects which should be taken into account, and the still-open questions, in order to make 3D printing a suitable manufacturing route for pediatric drugs.     

Pesticide-Induced Immunotoxicity: Are Humans at Risk?

One of the first immunotoxicology studies determined that exposure of ducks to DDT reduced their resistance to a virus infection. The immunotoxic potential of insecticides and herbicides has subsequently been studied extensively in laboratory animals, driven by the global distribution and use of these chemicals. (Ten of the twelve persistent organic pollutants, identified by the United Nations Environmental Program as posing the greatest threat to humans and wildlife, are pesticides; all have been reported to alter immune function under laboratory conditions.) Nevertheless, our knowledge of the human health risks associated with pesticide use and exposure is far from complete. This paper provides a brief overview of the potential effects of chemicals on the immune system, and host factors that mitigate or exacerbate immunotoxic effects. Examples of rodent studies that exemplify categories of pesticide-induced immune system effects are then provided as an introduction to a discussion of pesticide immunotoxicity in humans.     

Barriers to Participation in a Patient Satisfaction Survey: Who Are We Missing?

Background

A common weakness of patient satisfaction surveys is a suboptimal participation rate. Some patients may be unable to participate, because of language barriers, physical limitations, or mental problems. As the role of these barriers is poorly understood, we aimed to identify patient characteristics that are associated with non-participation in a patient satisfaction survey.

Methodology

At the University Hospitals of Geneva, Switzerland, a patient satisfaction survey is regularly conducted among all adult patients hospitalized for >24 hours on a one-month period in the departments of internal medicine, geriatrics, surgery, neurosciences, psychiatry, and gynaecology-obstetrics. In order to assess the factors associated with non-participation to the patient satisfaction survey, a case-control study was conducted among patients selected for the 2005 survey. Cases (non respondents, n = 195) and controls (respondents, n = 205) were randomly selected from the satisfaction survey, and information about potential barriers to participation was abstracted in a blinded fashion from the patients'' medical and nursing charts.

Principal Findings

Non-participation in the satisfaction survey was independently associated with the presence of a language barrier (odds ratio [OR] 4.53, 95% confidence interval [CI95%]: 2.14–9.59), substance abuse (OR 3.75, CI95%: 1.97–7.14), cognitive limitations (OR 3.72, CI95%: 1.64–8.42), a psychiatric diagnosis (OR 1.99, CI95%: 1.23–3.23) and a sight deficiency (OR 2.07, CI95%: 0.98–4.36). The odds ratio for non-participation increased gradually with the number of predictors.

Conclusions

Five barriers to non-participation in a mail survey were identified. Gathering patient feedback through mailed surveys may lead to an under-representation of some patient subgroups.     

Risk Sensitivity in Behavior: Where Are We Now? Introduction to the Symposium

Risk-sensitive behavior is the phenomenon of animals exhibitingpreferences when offered choices whose outcomes differ in theirdegree of variance. It is now well demonstrated that many animalsare sensitive to differences in the magnitude of variance inrewards. A considerable body of literature on risk sensitivityhas been generated in recent years, encompassing theoreticaland empirical work, from both functional and mechanistic approaches.Nevertheless, it is less than clear how animal preferences forvariability are determined. It is therefore timely to look broadlyat what has been accomplished, and to identify the most promisingsynthetic approaches for future work.     

Strategies to Combat Coccidioidomycosis: Are We Making Any Progress?

Coccidioidomycosis is caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. One of the endemic mycoses, this organism has been found solely in the semiarid to arid life zones of the southwestern United States, Mexico, and parts of Central America and South America. Clinical manifestations of disease vary greatly between patients and are largely dependent upon both the extent of exposure and the immune status of the host. The incidence of coccidioidomycosis continues to rise within the United States. Primary coccidioidal pneumonia accounts for close to 25% of all community-acquired pneumonia within endemic regions, reflecting the substantial burden of disease and health care costs associated with this infection. Although most patients with coccidioidomycosis resolve their initial infection without long-term complications, a minority of patients develop complications of disease ranging from asymptomatic pulmonary nodules to life-threatening disease such as meningitis. This review focuses on the epidemiology, clinical manifestations, spectrum of disease, and treatment options currently available for coccidioidomycosis.     

When Are We Most Vulnerable to Temperature Variations in a Day?

Daily temperature measures are commonly used when examining the association between temperature and mortality. In fact, temperature measures are available 24 hours a day and more detailed records may provide a better prediction of mortality compared to daily statistics. In this article, monthly stratified analysis modeling for mortality is conducted for the total population as well as the stratified elderly and younger subgroups. We identified the most significant time during the day that is associated with daily mortality. Surprisingly, the estimates of relative risk and magnitude of associations derived from the hourly temperature measures are similar or even stronger compared to those modeled by the daily statistics. This phenomenon remains true for lagged hourly temperature measures and the changing patterns of associations from January through December are revealed. In summary, people are the most vulnerable to temperature variations in the early morning around 5 am and the night time around 8 pm.     

Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.     

Quality-by-Design: Are We There Yet?

In 2012, the Quality-by-Design and Product Performance Focus Group of AAPS conducted a survey to assess the state of adoption and perception of Quality-by-Design (QbD). Responses from 149 anonymous individuals from industry—including consultants—(88%), academia (7%), and regulatory body (4%), were collected. A majority of respondents (54% to 76%) reported high frequency of utilization of several tools and most QbD elements outlined by International Conference on Harmonization Q8, with design of experiments, risk assessment, and the quality target product profile ranked as the top three. Over two thirds of respondents agreed that the benefits of QbD included both the positive impact it can have on the patient (78%), as well as on internal processes such as knowledge management (85%), decision making (79%), and lean manufacture (71%). However, more than 50% from industry were neutral about or disagreed with QbD leading to a better return on investment. This suggests that, despite the recognized scientific, manufacture, and patient-related benefits, there is not yet a clearly articulated business case for QbD available. There was a difference of opinion between industry and regulatory agency respondents as to whether a QbD-based submission resulted in increased efficiency of review. These contrasting views reinforce the idea that QbD implementation can benefit from further dialog between industry and regulatory authorities. A majority of respondents from academia indicated that QbD has influenced their research. In total, the results indicate the broad adoption of QbD but also suggest we are yet in a journey and that the process of gathering all experience and metrics required for connecting and demonstrating QbD benefits to all stakeholders is still in progress.     

Are We Misinterpreting Seed Predation in Palms?

The inadvertent inclusion of weevil‐infested seeds when evaluating seed predation by vertebrates, and particularly rodents, may lead to an overestimation of predation rates, thereby confusing the roles of rodents and invertebrates as ecological filters. A study of weevils, rodents and Syagrus romanzoffiana palm seeds indicates the usefulness of X‐rays to improve evaluation of invertebrate seed predation.     

Aging: all in the head?

Global reduction in insulin signaling has been linked to extended life span in a range of organisms. New work on mice with brain-specific or whole-body reductions in insulin receptor substrate 2 (IRS2) (Taguchi et al., 2007) points to a role for insulin/IGF-1 signaling in the central control of mammalian aging.