Selenium and diabetes: an enigma?

In recent years diabetes has become one of the most common metabolic diseases in developed countries and it is closely related to supernutrition and obesity. Since untreated diabetes produces oxidative stress responsible for secondary complications of the disease, antioxidant supplements were considered as being favourable for the therapy of diabetes. However, the situation has changed recently, since large cross-sectional and interventional trials revealed a positive correlation between a high Se status and diabetes incidence in humans. Thus, currently available data on the role of Se in diabetes are inconsistent and an enigma appears to exist for the relation between selenium and diabetes. This review summarizes selected human and animal studies, pointing to beneficial and critical virtues of Se in diabetes. Moreover, the review discusses possible underlying mechanisms how Se may influence diabetes in both directions. From the current literature, the following information can be extracted: (1) In populations with a high Se status, with the single exception of pregnant women, Se supplements cannot be recommended for the prevention of diabetes; (2) Anti-diabetic effects of Se seem to be restricted to high and nearly toxic doses which cannot be used in humans; and (3) Future investigations should consider the stage of the disease.     

Genetics: still a discipline?

In the institutional sense of the term "discipline" (laboratories, societies, congresses, curricula, etc.), genetics remains a discipline. In the intellectual sense of the term (consensus on a definite array of concepts, methods and theoretical purposes), it is doubtful that genetics is still a discipline. At first, molecular biology seemed to have introduced an unequivocal structural (or molecular) definition of the gene: a definite sequence of nucleotides that code for a protein. In fact, as it appears in retrospect, this was not the case. Even in 1961, when Jacob and Monod proposed their first model of genetic regulation in bacteria, there was no possibility of constructing a non equivocal concept of the gene. More recent developments in molecular genetics have made this situation worse. There is no possible definition of the gene as a general category. The reasons why biologists keep the word are pragmatic rather than theoretical: communication among scientists, economic interests and ideology.     

Costs of immune defense: an enigma wrapped in an environmental cloak?

Host defense against parasites and pathogens has been recognized as a costly life-history trait that can generate trade-offs with other fitness components. However, universality of immunological costs and associated trade-offs remains questionable in animal–parasite systems. This discrepancy could be a result of environmental effects, which have the potential to modulate the detection of trade-offs associated with immune function. Here, attention is drawn to the role that environmental factors can play in the manifestation and detection of costs associated with immune function and resistance. Moreover, we stress the importance of considering multiple external factors, host ontogeny and estimates of immunological function in studies investigating immune-related costs in animals.     

The 1989 James A. F. Stevenson memorial lecture. The knee jerk: still an enigma?

This is a wide-ranging review of muscle proprioceptors, intended primarily for the nonspecialist. It emphasizes how much more they are concerned with, than just the production of the knee jerk; it concentrates on principle rather than documenting detail and cites selectively. The main topics covered are the effect of deafferentation, position sense, the proprioceptors themselves, the control of the muscle spindle by the CNS, and spinal and long-latency "stretch" reflexes. The emphasis is on human work. The knee jerk itself is seen as a "physiological artefact," resulting from a mode of stimulation that does not occur in life, with the normal function of its underlying circuitry still under debate.     

The exercise ECG: still a useful exercise?

What is wrong with traditional ST-segment criteria during the exercise ECG? As we all know from daily practice, poor sensitivity of the exercise ECG for the detection of myocardial ischaemia is a major diagnostic weakness and a critical limitation of the exercise procedure. In standard meta-analyses, 1.0 mm (0.1 mV) of horizontal or downward-sloping ST depression has a sensitivity of only 68% for the detection of coronary artery disease (CAD), and this figure is even lower for women. This might explain our increasing reliance on noninvasive imaging modalities such as nuclear imaging (SPECT), magnetic resonance imaging (MRI), and computed tomography angiography (CTA), all of which show sensitivities between 80 and 90% for detecting CAD. As a result, there is a tendency to consider the exercise ECG as a poor man’s procedure to demonstrate myocardial ischaemia due to CAD. Is this the right consideration?     

Neuronal glucose sensing: still a physiological orphan?

Although hypothalamic glucose sensing is a long-established phenomenon, its physiological role remains unclear. New studies (Parton et al., 2007; Claret et al., 2007) disrupting glucose sensing in pro-opiomelanocortin neurons via differing methods have yielded disparate energy and glucose homeostasis phenotypes, suggesting that neuronal glucose sensing is not critical for these processes.     

Croatia: still a low-level HIV epidemic?--seroprevalence study

Central Europe is a region with a low prevalence of infection with human immunodeficiency virus (HIV). Until the end of 2007, 663 HIV cases were recorded in Croatia, almost exclusively among most at-risk populations. The aim of this research was to determine the HIV prevalence among most at-risk populations and the level of the HIV epidemic in Croatia. According to the World Health Organization classification there are three levels of HIV epidemics: generalized (prevalence in general population > 1%), concentrated (prevalence in general population < 1% and prevalence in at least one of the most at-risk populations > 5%) and low-level epidemic (prevalence in general population < 1% and prevalence in each most at-risk population < 5%). This was a research with convenience samples of most at-risk populations. The respondents were recruited by their peers, all non-governmental organizations that provide services for most at-risk populations and the researchers. Sera were tested using the fourth generation enzyme-linked fluorescent assay (EIA test) and reactive test were confirmed using the Western Blot test. In this research, the highest HIV prevalence was found within the men who have sex with men group (7/232 = 3%, 95% CI = 1.3-6.3%) and commercial sex workers (1/70 = 1.4%, 95% CI = 1-7.8%). In these samples we were unable to determine whether Croatia is facing a low-level epidemic due to the fact that the prevalences were not statistically significantly lower than 5% (p = 0.115 and p = 0.1, respectively). For the remaining samples the prevalence was statistically significantly lower than 5%, which points to a low-level epidemic. The prevalences in these samples were 7/593 = 1.2% (95% CI = 0.5-2.4%) in people with more than two sexual partners within the last 12 months, 2/249 = 0.8% (95% CI = 0-2.9%) in people with sexually transmitted infections in history, 2/317 = 0.6% (95% CI = 0-2.2%) in clients of sexual workers, 2/323 = 0.6% (95% CI = 0-2.2%) in injecting drug users and 0.2% (95% CI = 0-1%) in the sample of migrant workers. Based on the results of this survey, Croatia would be classified as having a low-level HIV epidemic although the confidence limits in two most-at-risk groups, men who have sex with men and commercial sex workers, overlap 5%.     

Xylem-borne cytokinins: still in search of a role?

Leaf expansion and xylem cytokinin concentration ([X-CK]) decrease in response to nitrogen (N) deprivation. Debate continues over cause, effect, and correlation. Supporting studies provide, at best, correlative evidence that [X-CK] controls leaf growth in response to N-deprivation, while dissenting studies indicate that leaf growth responses to N can be independent of changes in X-CK supply to leaves. A model is proposed to evaluate the physiological significance to leaf growth of changes in plant and environment N concentrations, and plant CK concentrations.     

Lipoprotein lipase, a key role in atherosclerosis?

Enzymes from hyperthermophiles can be efficiently purified after expression in mesophilic hosts and are well-suited for crystallisation attempts. Two enzymes of histidine biosynthesis from Thermotoga maritima, N'-((5'-phosphoribosyl)-formimino)-5-aminoimidazol-4-carb oxamid ribonucleotide isomerase and the cyclase moiety of imidazoleglycerol phosphate synthase, were overexpressed in Escherichia coli, both in their native and seleno-methionine-labelled forms, purified by heat precipitation of host proteins and crystallised. N'-((5'-phosphoribosyl)-formimino)-5-aminoimidazol-4-carb oxamid ribonucleotide isomerase crystallised in four different forms, all suitable for X-ray structure solution, and the cyclase moiety of imidazoleglycerol phosphate synthase yielded one crystal form that diffracted to atomic resolution. The obtained crystals will enable the determination of the first three-dimensional structures of enzymes from the histidine biosynthetic pathway.     

Cyprinotus incongruens (Ostracoda): an ancient asexual?

Although unisexual ostracods are common, their evolutionary history is now known only from inferences gained through examination of the fossil record. Here we use mtDNA, allozyme and genome size analyses to investigate the origins of unisexuality, polyploidy and clonal diversity in the freshwater ostracod Cyprinotus incongruens . Our genetic evidence suggests that transitions to polyploidy have been common in this taxon and may sometimes involve internal genome-fusion events, in contrast to the usual origin of animal polyploids through interspecific hybridization. Both the extent and congruent patterns of allozyme and mtDNA divergence amongst clones of C. incongruens are consistent with its persistence as an asexual taxon for approximately 5 million years. However, the detected patterns of genetic variation might also reflect the origins of this ostracod through a series of independent transitions to asexuality by several closely related ancestral taxa. The results make it clear that efforts to demonstrate the antiquity of asexual taxa, solely from surveys of the extent of genetic divergence among their component lineages, will ordinarily be ambiguous, requiring confirmation through investigations which search the genome for the genetic consequences of long abandoned recombination.     

Is being a doctor still fun?

Over the past two decades, a decline in physician job and career satisfaction has been reported. This study was developed to determine the current state of physician satisfaction and to define factors correlated with overall satisfaction. We mailed a survey to 406 physicians in Solano County, California. Responses were anonymous, and data were analyzed by several methods. Of the 406 physicians, 251 (62%) responded. Most respondents were satisfied with their jobs (80%). The vast majority felt good about their ability to help their patients (92%), enjoyed the relationships they had with patients (93%) and colleagues (86%), and found their work intellectually satisfying (89%). Nearly two thirds (63%) of respondents thought their job was "fun." This ability to derive great pleasure from work showed the strongest correlation with overall satisfaction. Overall satisfaction did not differ between primary care and non-primary care physicians or between physicians in a large health maintenance organization and those in mostly solo and small-group fee-for-service practices. Despite substantial challenges to physician morale and autonomy, most responding physicians in our study continued to enjoy overall job satisfaction, and a solid majority thought that their work was fun.     

Interleukin 12: still a promising candidate for tumor immunotherapy?

Interleukin 12 (IL-12) seemed to represent the ideal candidate for tumor immunotherapy, due to its ability to activate both innate (NK cells) and adaptive (cytotoxic T lymphocytes) immunities. However, despite encouraging results in animal models, very modest antitumor effects of IL-12 in early clinical trials, often accompanied by unacceptable levels of adverse events, markedly dampened  hopes of the successful use of this cytokine in cancer patients. Recently, several clinical studies have been initiated in which IL-12 is applied as an adjuvant in cancer vaccines, in gene therapy including locoregional injections of IL-12 plasmid and in the form of tumor-targeting immunocytokines (IL-12 fused to monoclonal antibodies). The near future will show whether this renewed interest in the use of IL-12 in oncology will result in meaningful therapeutic effects in a select group of cancer patients.