Hospital hypoglycemia: From observation to action

Background: A preponderance of evidence indicates that when treatment of hyperglycemia with insulin is provided for certain hospitalized populations, the attainment of appropriate glycemic targets improves nonglycemic outcomes such as mortality rates, morbidities (eg, wound infection, critical illness polyneuropathy, bacteremia, new renal insufficiency), duration of ventilator dependency, transfusion requirements, and length of hospital stay. Nevertheless, randomized controlled trials (RCTs) of intensive insulin therapy and studies of outcomes before and after implementation of tight glycemic control have consistently recognized an increased incidence of hypoglycemia as a complication associated with the use of lower glycemic targets and higher doses of insulin.Objectives: This commentary compares the quality of the available evidence on the clinical impact of iatrogenic hypoglycemia. We present treatment strategies designed to prevent iatrogenic hypoglycemia in the hospital setting.Methods: The PubMed database and online citations of articles tracked subsequent to publication were searched for articles on the epidemiology, clinical impact, and mechanism of harm of hypoglycemia published since 1986. In addition, we searched the literature for RCTs conducted since 2001 concerning intensive insulin therapy in the hospital critical care setting, including meta-analyses; letters to the editor were excluded. The retrieved studies were scanned and chosen selectively for full-text review based on the study size and design, novelty of findings, and evidence related to the possible clinical impact of hypoglycemia. Reference lists from the retrieved studies were searched for additional studies. Reports were summarized for the purpose of comparing and contrasting the qualitative nature of information about iatrogenic hypoglycemia in the hospital.Results: Eight RCTs of intensive glycemic management, 16 observational studies of hospitalized patients with hypoglycemia (including studies of outcomes before and after implementation of tight glycemic control), and 4 case reports on patients with hypoglycemia were selected for discussion of the incidence of hypoglycemia, significance of hypoglycemia as a marker or cause of poor prognosis, and clinical harm of hypoglycemia. Hypoglycemia was identified in clinical trials as either a category of adverse events or a complication of intensified insulin treatment. For example, a recent meta-analysis found that the incidence of severe hypoglycemia was higher among critically ill patients treated with intensive insulin therapy than among control patients, with a pooled relative risk of 6.0 (95% CI, 4.5–8.0). In the largest multisite RCT on glycemic control among patients in intensive care units (ICUs) conducted to date, deaths were reported for 27.5% (829/3010 patients) in the intensive-treatment group and 24.9% (751/3012 patients) in the conventional-treatment group (odds ratio, 1.14; 95% CI, 1.02–1.28; P = 0.02). In another multisite ICU study, although the intensive and control groups had similar mortality rates, the mortality rate was higher among hypoglycemic participants than among nonhypoglycemic participants (32.2% vs 13.6%, respectively; P < 0.01). Pooled data from 2 singlesite studies in medical and surgical ICUs revealed an increased risk of hypoglycemia in the intensive-treatment group compared with the conventional-treatment group (11.3% [154/1360] and 1.8% [25/1388], respectively; P < 0.001), but the hospital mortality rate was similar for the 2 groups (50.6% [78/154] and 52.0% [13/25], respectively). Specific sequelae of hypoglycemia affecting individual patients were described in the RCTs as well as in the observational studies. New guidelines for glycemic control have recently been issued, but results of the studies using the new targets are not yet available. We propose treatment strategies designed to prevent iatrogenic hypoglycemia in the hospital setting.Conclusions: In response to the growing evidence on the risk of hypoglycemia during intensified glycemic management of hospitalized patients, professional organizations recently revised targets for glycemic control. It is appropriate for institutions to reevaluate hospital protocols for glycemic management with intravenous insulin and, on general wards, to implement standardized order sets for use of subcutaneous insulin to achieve beneficial targets using safe strategies.     

Pain perception, aversion and fear in fish

There is now compelling evidence that teleost fish possess similar nociceptive processing systems to those found in terrestrial vertebrates. Noxious stimulation of these nociceptors--specialised pain receptors -in the skin around the snout of fish generates neural activity that can be electrophysiologically recorded, and induces a number of behavioural and physiological changes. To determine whether changes in behaviour are more than simple responses to the noxious stimulation it is necessary to demonstrate that higher order cognitive processes such as mental state or 'affective state' are involved. However, quantifying the 'motivational affected state' of an animal--a concept encompassing not just pain but also fear, hunger, thirst and pleasure - is difficult owing to its subjectivity. Recent empirical work is beginning to test these concepts in fish, and we review a number of these studies and suggest how these general methodologies could be used to further our understanding of fish cognition and the capacity for fish to experience mental states such as fear or suffering.     

Patterns of genetic variation in populations of infectious agents

Background  

The analysis of genetic variation in populations of infectious agents may help us understand their epidemiology and evolution. Here we study a model for assessing the levels and patterns of genetic diversity in populations of infectious agents. The population is structured into many small subpopulations, which correspond to their hosts, that are connected according to a specific type of contact network. We considered different types of networks, including fully connected networks and scale free networks, which have been considered as a model that captures some properties of real contact networks. Infectious agents transmit between hosts, through migration, where they grow and mutate until elimination by the host immune system.     

Similar hypotensive responses to resistance exercise with and without blood flow restriction

Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances.     

Disentangling the relative importance of climate,size and competition on tree growth in Iberian forests: implications for forest management under global change

Most large‐scale multispecies studies of tree growth have been conducted in tropical and cool temperate forests, whereas Mediterranean water‐limited ecosystems have received much less attention. This limits our understanding of how growth of coexisting tree species varies along environmental gradients in these forests, and the implications for species interactions and community assembly under current and future climatic conditions. Here, we quantify the absolute effect and relative importance of climate, tree size and competition as determinants of tree growth patterns in Iberian forests, and explore interspecific differences in the two components of competitive ability (competitive response and effect) along climatic and size gradients. Spatially explicit neighborhood models were developed to predict tree growth for the 15 most abundant Iberian tree species using permanent‐plot data from the Spanish Second and Third National Forest Inventory (IFN). Our neighborhood analyses showed a climatic and size effect on tree growth, but also revealed that competition from neighbors has a comparatively much larger impact on growth in Iberian forests. Moreover, the sensitivity to competition (i.e. competitive response) of target trees varied markedly along climatic gradients causing significant rank reversals in species performance, particularly under xeric conditions. We also found compelling evidence for strong species‐specific competitive effects in these forests. Altogether, these results constitute critical new information which not only furthers our understanding of important theoretical questions about the assembly of Mediterranean forests, but will also be of help in developing new guidelines for adapting forests in this climatic boundary to global change. If we consider the climatic gradients of this study as a surrogate for future climatic conditions, then we should expect absolute growth rates to decrease and sensitivity to competition to increase in most forests of the Iberian Peninsula (in all but the northern Atlantic forests), making these management considerations even more important in the future.     

Some p53-binding proteins that can function as arbiters of life and death

Four sets of p53-binding proteins are discussed in this review. These are the E2F family, the ASPP family, Y-box-binding protein YB1, and the prolyl isomerase Pin1. Each appears to play a role in the decision by p53 to induce an arrest of cell proliferation or apoptosis and they may also be independent markers of cancer. Their activities appear to be linked with the cell cycle and they may also interact with each other. In this review, the properties of each protein class are discussed as well as how they affect p53 functions. A model is proposed as to how their activities might be coordinated.     

Single-nucleotide base excision repair DNA polymerase activity in C. elegans in the absence of DNA polymerase β

The base excision DNA repair (BER) pathway known to occur in Caenorhabditis elegans has not been well characterized. Even less is known about the DNA polymerase (pol) requirement for the gap-filling step during BER. We now report on characterization of in vitro uracil-DNA initiated BER in C. elegans. The results revealed single-nucleotide (SN) gap-filling DNA polymerase activity and complete BER. The gap-filling polymerase activity was not due to a DNA polymerase β (pol β) homolog, or to another X-family polymerase, since computer-based sequence analyses of the C. elegans genome failed to show a match for a pol β-like gene or other X-family polymerases. Activity gel analysis confirmed the absence of pol β in the C. elegans extract. BER gap-filling polymerase activity was partially inhibited by both dideoxynucleotide and aphidicolin. The results are consistent with a combination of both replicative polymerase(s) and lesion bypass/BER polymerase pol θ contributing to the BER gap-filling synthesis. Involvement of pol θ was confirmed in experiments with extract from pol θ null animals. The presence of the SN BER in C. elegans is supported by these results, despite the absence of a pol β-like enzyme or other X-family polymerase.