Can we consider medical residents as shift workers?

Although medical residents are characterized by long working hours, night shifts and high levels of work load, it is unclear if their work schedule can be classified as shift work, or if it has a similar impact on residents' well-being. The present paper compared the profile of complaints about sleep or daytime functioning of medical residents to that of rotating shift workers and day workers, of similar ages. Sixty-one residents (aged: 32.2 +/- 2.2 years), after 2 years of residency, participated in the study. The two control groups with a similar age range (26-40 years) were chosen, and included 94 rotating shift workers and 146 day workers. All subjects completed self-administered questionnaires on their sleep habits, and their sleep-wake cycle was monitored by a wrist-worn actigraph. Ten percent of the residents complained about difficulties falling asleep, 34% complained about morning tiredness, 14% complained about mid-sleep awakening, and 20% about prolonged fatigue. The residents slept significantly less than the day workers, and their sleep efficiency was significantly higher. When examining their subjective complaints profile, residents complained more than day workers and their answers were more similar to those of rotating shift workers, therefore they can be considered to be characterized as shift workers.     

Phlebotomine sand flies and Leishmania parasites: friends or foes?

Leishmania parasites need phlebotomine sand flies to complete their life cycle and to propagate. This review looks at Leishmania-sand fly interactions as the parasites develop from amastigotes to infectious metacyclics, highlighting recent findings concerning the evolutionary adaptations that ensure survival of the parasites. Such adaptations include secretion of phosphoglycans, which protect the parasite from digestive enzymes; production of chitinases that degrade the stomodeal valve of the sand fly; secretion of a neuropeptide that arrests midgut and hindgut peristalsis; and attaching to the midgut to avoid expulsion.     

Sustainable systems as organisms?

Schrödinger [Schrödinger, E., 1944. What is Life? Cambridge University Press, Cambridge] marvelled at how the organism is able to use metabolic energy to maintain and even increase its organisation, which could not be understood in terms of classical statistical thermodynamics. Ho [Ho, M.W., 1993. The Rainbow and the Worm, The Physics of Organisms, World Scientific, Singapore; Ho, M.W., 1998a. The Rainbow and the Worm, The Physics of Organisms, 2nd (enlarged) ed., reprinted 1999, 2001, 2003 (available online from ISIS website www.i- sis.org.uk)] outlined a novel “thermodynamics of organised complexity” based on a nested dynamical structure that enables the organism to maintain its organisation and simultaneously achieve non-equilibrium and equilibrium energy transfer at maximum efficiency. This thermodynamic model of the organism is reminiscent of the dynamical structure of steady state ecosystems identified by Ulanowicz [Ulanowicz, R.E., 1983. Identifying the structure of cycling in ecosystems. Math. Biosci. 65, 210–237; Ulanowicz, R.E., 2003. Some steps towards a central theory of ecosystem dynamics. Comput. Biol. Chem. 27, 523–530].The healthy organism excels in maintaining its organisation and keeping away from thermodynamic equilibrium – death by another name – and in reproducing and providing for future generations. In those respects, it is the ideal sustainable system. We propose therefore to explore the common features between organisms and ecosystems, to see how far we can analyse sustainable systems in agriculture, ecology and economics as organisms, and to extract indicators of the system's health or sustainability.We find that looking at sustainable systems as organisms provides fresh insights on sustainability, and offers diagnostic criteria for sustainability that reflect the system's health.In the case of ecosystems, those diagnostic criteria of health translate into properties such as biodiversity and productivity, the richness of cycles, the efficiency of energy use and minimum dissipation. In the case of economic systems, they translate into space-time differentiation or organised heterogeneity, local autonomy and sufficiency at appropriate levels, reciprocity and equality of exchange, and most of all, balancing the exploitation of natural resources – real input into the system – against the ability of the ecosystem to regenerate itself.     

Fibroblast sources: Where can we get them?

Fibroblasts are cells widely used in cell culture, both for transient primary cell culture or permanent as transformed cell lines. Lately, fibroblasts become cell sources for use in disease modeling after cell reprogramming because it is easily accessible in the body. Fibroblasts in patients will maintain all genetic background during reprogramming into induced pluripotent stem cells. In spite of their large use, fibroblasts are obtained after an invasive procedure, a superficial punch skin biopsy, collected under patient’s local anesthesia. Taking into consideration the minimum patient’s discomfort during and after the biopsy procedure, as well as the aesthetics aspect, it is essential to reflect on the best site of the body for the biopsy procedure combined with the success of getting robust fibroblast cultures in the lab. For this purpose, we compared the efficiency of four biopsy sites of the body (skin from eyelid, back of the ear, abdominal cesarean scar and groin). Cell proliferation assays and viability after cryopreservation were measured. Our results revealed that scar tissue provided fibroblasts with higher proliferative rates. Also, fibroblasts from scar tissues presented a higher viability after the thawing process.     

Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites?

Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L. aethiopica and L. tropica, were tested for their ability to interfere with apoptosis in host macrophages in 2 different lines of human monocyte-derived macrophages (cell lines THP-1 and U937) and the results confirmed in peripheral blood mononuclear cells (PBMC). All 3 species induced early apoptosis 48 h after infection (expression of phosphatidyl serine on the outer membrane). There were significant increases in the percentage of apoptotic cells both for U937 and PBMC following infection with each of the 3 species. Early apoptotic events were confirmed by mitochondrial membrane permeabilization detection and caspase activation 48 and 72 h after infection. Moreover, the percentage of infected THP-1 and U937 macrophages increased significantly (up to 100%) following treatment with an apoptosis inducer. Since phosphatidyl serine externalization on apoptosing cells acts as a signal for engulfment by macrophages, induction of apoptosis in the parasitized cells could actively participate in spreading the infection. In summary, parasite-containing apoptotic bodies with intact membranes could be released and phagocytosed by uninfected macrophages.     

Emerging waterborne pathogens: can we kill them all?

The rapid emergence of Cryptosporidium parvum and Escherichia coli 0157:H7 have created a threat to the drinking water industry and there is a growing need to develop a strategy for recognizing potential emerging waterborne pathogens. Globalization of trade, changing population demographics and changes in treatment technology have been driving factors in the emergence of these new pathogens. An understanding of disinfectant action and microbial resistance to treatment processes is needed to better identify those pathogens likely to be of greatest concern. Recent research on microbial resistance to treatment and disinfection demonstrates that the microbial surface structure and composition and the nature of the genome are key to determining the potential for waterborne transmission of emerging pathogens.     

Imaging for lung physiology: what do we wish we could measure?

The role of imaging as a tool for investigating lung physiology is growing at an accelerating pace. Looking forward, we wished to identify unresolved issues in lung physiology that might realistically be addressed by imaging methods in development or imaging approaches that could be considered. The role of imaging is framed in terms of the importance of good spatial and temporal resolution and the types of questions that could be addressed as these technical capabilities improve. Recognizing that physiology is fundamentally a quantitative science, a recurring emphasis is on the need for imaging methods that provide reliable measurements of specific physiological parameters. The topics included necessarily reflect our perspective on what are interesting questions and are not meant to be a comprehensive review. Nevertheless, we hope that this essay will be a spur to physiologists to think about how imaging could usefully be applied in their research and to physical scientists developing new imaging methods to attack challenging questions imaging could potentially answer.     

Hemophagocytic syndrome--should we consider it more often?

Hemophagocytic syndrome (HPS) is a rare condition characterized by overactive histiocytes, hepatosplenomegaly, fever and cytopenia, with two major types: familial, autosomal recessive genetic disease and acquired that can occur during systemic infections, immunodeficiency or malignancy. Inappropriate activation of macrophages by cytokines is the major mechanism of the disease. We report a case of an adult patient with HPS. After thorough clinical investigation, we have not been able to establish the underlying disease, and corticosteroids therapy was initiated empirically. After 8 months follow-up the patient is well with normal laboratory findings.     

Is sleep per se a zeitgeber in humans?

It is not clear whether shifting of sleep per se, without a concomitant change in the light-dark cycle, can induce a phase shift of the human circadian pacemaker. Two 9-day protocols (crossover, counterbalanced order) were completed by 4 men and 6 women (20-34 years) after adherence to a 2330 to 0800 h sleep episode at home for 2 weeks. Following a modified baseline constant routine (CR) protocol on day 2, they remained under continuous near-darkness (< 0.2 lux, including sleep) for 6 days. Four isocaloric meals were equally distributed during scheduled wakefulness, and their timing was held constant. Subjects remained supine inbed from 2100 to 0800 h on all days; sleep was fixed from 2330 to 0800 h in the control condition and was gradually advanced 20 min per day during the sleep advance condition until a 2-h difference had been attained. On day 9, a 25 to 27 h CR protocol (approximately 0.1 lux) was carried out. Phase markers were the evening decline time of the core body temperature (CBT) rhythm and salivary melatonin onset (3 pg/ml threshhold). In the fixed sleep condition, the phase drift over 7 days ranged from +1.62 to -2.56 h (for both CBT and melatonin rhythms, which drifted in parallel). The drifts were consistently advanced in the sleep advance schedule by +0.66 +/- 0.23 (SEM) h for CBT (p = 0.02) and by 0.27 +/- 0.14 h for melatonin rhythms (p = 0.09). However, this advance was small to medium according to effect size. Sleep per se may feed back onto the circadian pacemaker, but it appears to be a weak zeitgeber in humans.     

Resistance to xenobiotics and parasites: can we count the cost?

The nature and cost of single genes of major effect is one of the longest running controversies in biology. Resistance, whether to xenobiotics or to parasites, is often paraded as an obvious example of a single gene effect that must carry an associated fitness 'cost'. However, a review of the xenobiotic resistance literature shows that empirical evidence for this hypothesis is, in fact, scarce. We postulate that such fitness costs can only be fully interpreted in the light of the molecular mutations that might underlie them. We also derive a theoretical framework both to encompass our current understanding of xenobiotic resistance and to begin to dissect the probable cost of parasite resistance.     

Basic concepts in nervous system: Are the nerves wired as we have thought them to be?

Fundamentals of neurology as passed down through the instruction of medical schooling say that nerves are broadly classified into three types; namely the motor, sensory and mixed nerves. But, is this truly so with regard to cranial nerves? This short communication aims at cautioning the pioneers, experts and medical instructors in the field of neurology about the use of misconstrued terminology in the basic concepts of nervous system. May be it is time for us to re-visit the basics of neurology?     

Do bumblebees always forage as much as they could?

Summary Bumblebees must forage to provide food to the colony. However, foraging is costly as worker longevity is inversely related to foraging effort. Given this trade-off, workers from colonies with abundant food supplies could either maintain foraging to increase reserves for future use or forage less to avoid the associated costs. We tested these hypotheses over one summer, using 13 pairs of field colonies of Bombus impatiens. Half of the colonies were provided with a sucrose solution ad libitum and pollen at regular intervals throughout their entire development, while the other half served as controls. We measured the forager activity rates in colonies with infra-red motion detectors fit in nest box entrances. However, due to reasons beyond our control (loss of the queen, usurpation by Psithyrus, debris in the entrance tunnel, etc.), we could use data from only two pairs of colonies for the analysis. Food supplemented colonies had a forager activity rate per worker 25% lower than controls which supports the hypothesis that workers reduce risks when given the opportunity.Received 15 May 2003; revised 15 January 2004; accepted 19 February 2004.     

Denatured bactericidal proteins: Active per se,or reservoirs of active peptides?

According to the structure-to-function paradigm proteins fold into a 3D structure for exerting their functions. Intrinsically destructured proteins with important biological functions have been identified and studied, but they assume a structure when interacting in the cell with their partners. There are instead bactericidal proteins, endowed also with other diverse activities (glycoside hydrolases, RNases, a defensin), which are lost when the proteins are denatured or inactivated, whereas the bactericidal activity is surprisingly conserved.The hypothesis is advanced that these proteins are not bactericidal per se, but because they store in their amino acid sequences peptide segments that display bactericidal activity when cut out as free peptides from the proteins. These bactericidal proteins would thus be merely containers of bactericidal peptides.     

Pathogenomics of fungal plant parasites: what have we learnt about pathogenesis?

Members of the kingdom fungi comprise numerous plant pathogens, including the causal agents of many agriculturally relevant plant diseases such as rust, powdery mildew, rice blast and cereal head blight. Data from recent sequencing projects provide deep insight into the genomes of a range of fungi that infect different organs of monocotyledonous or dicotyledonous hosts and that have diverse pathogenic lifestyles. These studies have revealed that, similar to sequenced phytopathogenic oomycetes, these plant parasites possess very plastic and dynamic genomes, which typically encode several hundred candidate secreted effector proteins that can be highly divergent even among related species. A new insight is the presence of lineage-specific genes on mobile and partly dispensable chromosomes that are transferred intraspecifically and possibly interspecifically, thereby constituting pathogenicity and host range determinants. Convergent lifestyle-specific adaptations have shaped the parasite genomes to maximize pathogenic success according to the different infection strategies employed.     

Lipids in cell biology: how can we understand them better?

Lipids are a major class of biological molecules and play many key roles in different processes. The diversity of lipids is on the same order of magnitude as that of proteins: cells express tens of thousands of different lipids and hundreds of proteins to regulate their metabolism and transport. Despite their clear importance and essential functions, lipids have not been as well studied as proteins. We discuss here some of the reasons why it has been challenging to study lipids and outline technological developments that are allowing us to begin lifting lipids out of their “Cinderella” status. We focus on recent advances in lipid identification, visualization, and investigation of their biophysics and perturbations and suggest that the field has sufficiently advanced to encourage broader investigation into these intriguing molecules.Lipids are fundamental building blocks of all cells and play many important and varied roles. They are key components of the plasma membrane and other cellular compartments, including the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, and trafficking vesicles such as endosomes and lysosomes. The lipid composition of different organelles, cell types, and ultimately tissues can vary substantially, suggesting that different lipids are required for different functions (Saghatelian et al., 2006 ; Klose et al., 2013 ). Mammalian cells express tens of thousands of different lipid species and use hundreds of proteins to synthesize, metabolize, and transport them. Although the complexity and diversity of lipids approach those of proteins, we have a much poorer understanding of their functions, making lipids in many ways the “Cinderellas” of cell biology. We discuss here recent advances, and challenges, in investigating how these molecules contribute to the many biological processes in which they participate.Like proteins, lipids can have structural (e.g., by stabilizing different membrane curvatures) or signaling roles. Posttranslational lipidation of proteins (e.g., palmitoylation or farnesylation) and carbohydrate-linked lipids (glycolipids) are also important examples of cellular lipid pools. It is clear that higher-order organization is key to most lipid functions, and they are believed to assemble into signaling platforms that contain both lipids and proteins (Kusumi et al., 2012 ). Some lipid microdomains are termed lipid rafts, and much ongoing effort is being focused on defining their parameters (Simons and Sampaio, 2011 ; Suzuki et al., 2012 ; Klotzsch and Schutz, 2013 ). Because of this focus on lipid rafts, we have a better understanding of the properties of proposed raft lipids (e.g., sphingomyelins and cholesterol) than of many other lipid species. Much of what we know about lipids has come from studying synthetic membranes with specific lipid compositions. Although model membranes usually consist of very few (<10) lipid species, they have been useful for understanding the biophysical properties of lipids. At the other end of the spectrum, lipids have been implicated in various diseases, with cholesterol metabolism being a prominent example. We are now getting to a point at which we can address the roles of lipids in the middle of the spectrum—in cells.     

Malarial parasites as geographical markers in migratory birds?

We tested the hypothesis that malarial parasites (Plasmodium and Haemoproteus) of black-throated blue warblers (Dendroica caerulescens) provide sufficient geographical signal to track population movements between the warbler's breeding and wintering habitats in North America. Our results from 1083 warblers sampled across the species' breeding range indicate that parasite lineages are geographically widespread and do not provide site-specific information. The wide distribution of malarial parasites probably reflects postnatal dispersal of their hosts as well as mixing of breeding populations on the wintering range. When compared to geographically structured parasites of sedentary Caribbean songbirds, patterns of malarial infections in black-throated blue warblers suggest that host-malaria dynamics of migratory and sedentary bird populations may be subject to contrasting selection pressures.