A Randomised Controlled Trial to Reduce Sedentary Time in Young Adults at Risk of Type 2 Diabetes Mellitus: Project STAND (Sedentary Time ANd Diabetes)

Aims

Type 2 diabetes mellitus (T2DM), a serious and prevalent chronic disease, is traditionally associated with older age. However, due to the rising rates of obesity and sedentary lifestyles, it is increasingly being diagnosed in the younger population. Sedentary (sitting) behaviour has been shown to be associated with greater risk of cardio-metabolic health outcomes, including T2DM. Little is known about effective interventions to reduce sedentary behaviour in younger adults at risk of T2DM. We aimed to investigate, through a randomised controlled trial (RCT) design, whether a group-based structured education workshop focused on sitting reduction, with self-monitoring, reduced sitting time.

Methods

Adults aged 18–40 years who were either overweight (with an additional risk factor for T2DM) or obese were recruited for the Sedentary Time ANd Diabetes (STAND) RCT. The intervention programme comprised of a 3-hour group-based structured education workshop, use of a self-monitoring tool, and follow-up motivational phone call. Data were collected at three time points: baseline, 3 and 12 months after baseline. The primary outcome measure was accelerometer-assessed sedentary behaviour after 12 months. Secondary outcomes included other objective (activPAL) and self-reported measures of sedentary behaviour and physical activity, and biochemical, anthropometric, and psycho-social variables.

Results

187 individuals (69% female; mean age 33 years; mean BMI 35 kg/m²) were randomised to intervention and control groups. 12 month data, when analysed using intention-to-treat analysis (ITT) and per-protocol analyses, showed no significant difference in the primary outcome variable, nor in the majority of the secondary outcome measures.

Conclusions

A structured education intervention designed to reduce sitting in young adults at risk of T2DM was not successful in changing behaviour at 12 months. Lack of change may be due to the brief nature of such an intervention and lack of focus on environmental change. Moreover, some participants reported a focus on physical activity rather than reductions in sitting per se. The habitual nature of sedentary behaviour means that behaviour change is challenging.

Trial Registration

Controlled-Trials.com ISRCTN08434554     

Seasonal changes in pod characteristics of eastern Australian humpback whales (Megaptera novaeangliae), Hervey Bay 1992–2005

We investigated the characteristics and composition of 4,506 humpback whale pods observed in Hervey Bay between 1992 and 2005. We use these data to analyze and model the variability of pod size and composition, and to assess the importance of Hervey Bay for particular classes of humpback whales. Pods ranged in size from one to nine individuals. Pairs were the most frequent pod type (1,344, 29.8%), followed by mother‐calf alone (1,249, 27.7%), trios (759, 16.8%), singletons (717, 15.9%), and 4+ whales (437, 9.7%). Of the 4,506 pods, calves were present in 40%, and 10.8% of all pods had one or more escorts present. Of the 1,804 pods observed with calves present, 1,251 (69.4%) were mothers alone with their calves. The size and composition of pods in the study area varied significantly as the season progressed. Pods with calves present were rarely recorded early in the season but dominated later in the season. A significant increase over years in larger groups may be related to social and behavioral changes as the population expands. The data indicate that Hervey Bay is important to immature males and females early in the season, to mature males and females in mid‐season, and to mother‐calf pairs (either alone or with escorts) in mid‐to‐late season.     

Conservation of a masked nuclear export activity of La proteins and its effects on tRNA maturation

La is an RNA-processing-associated phosphoprotein so highly conserved that the human La protein (hLa) can replace the tRNA-processing function of the fission yeast La protein (Sla1p) in vivo. La proteins contain multiple trafficking elements that support interactions with RNAs in different subcellular locations. Prior data indicate that deletion of a nuclear retention element (NRE) causes nuclear export of La and dysfunctional processing of associated pre-tRNAs that are spliced but 5' and 3' unprocessed, with an accompanying decrease in tRNA-mediated suppression, in fission yeast. To further pursue these observations, we first identified conserved residues in the NREs of hLa and Sla1p that when substituted mimic the NRE deletion phenotype. NRE-defective La proteins then deleted of other motifs indicated that RNA recognition motif 1 (RRM1) is required for nuclear export. Mutations of conserved RRM1 residues restored nuclear accumulation of NRE-defective La proteins. Some RRM1 mutations restored nuclear accumulation, prevented disordered pre-tRNA processing, and restored suppression, indicating that the tRNA-related activity of RRM1 and its nuclear export activity could be functionally separated. When mapped onto an hLa structure, the export-sensitive residues comprised surfaces distinct from the RNA-binding surface of RRM1. The data indicate that the NRE has been conserved to mask or functionally override an equally conserved nuclear export activity of RRM1. The data suggest that conserved elements mediate nuclear retention, nuclear export, and RNA-binding activities of the multifunctional La protein and that their interrelationship contributes to the ability of La to engage its different classes of RNA ligands in different cellular locations.     

All in the Family: Kin Contact Leads to Outer Membrane Exchange

The ability to recognize related cells in a population can confer evolutionary benefits. For example, some bacteria use contact-dependent inhibition proteins to distinguish kin from nonkin. Kinship recognition is taken to a new level in Myxococcus, which uses the dual-purpose TraA protein for kin recognition and outer membrane and lipoprotein exchange. In this issue of the Journal of Bacteriology, Wei et al. (X. Wei, C. N. Vassallo, D. T. Pathak, D. Wall, J. Bacteriol. 196:1807–1814, 2014) show that Tra-dependent exchange can be uncoupled from outer membrane vesicle/tube formation, reported elsewhere to mediate outer membrane exchange.     

Whales sustain fisheries: Blue whales stimulate primary production in the Southern Ocean

It has previously been asserted that baleen whales compete with fisheries by consuming potentially harvestable marine resources. The regularly applied “surplus‐yield model” suggests that whale prey becomes available to fisheries if whales are removed, and has been presented as a justification for whaling. However, recent findings indicate that whales enhance ecosystem productivity by defecating iron that stimulates primary productivity in iron‐limited waters. While juvenile whales and whales that are pregnant or lactating retain iron for growth and milk production, nonbreeding adult whales defecate most of the iron they consume. Here, we modify the surplus‐yield model to incorporate iron defecation. After modeling a simplistic trajectory of blue whale recovery to historical abundances, the traditional surplus‐yield model predicts that 10¹¹ kg of carbon yr^?1 would become unavailable to fisheries. However, this ignores the nutrient recycling role of whales. Our model suggests the population of blue whales would defecate 3 × 10⁶ kg of iron yr^?1, which would stimulate primary production equivalent to that required to support prey consumption by the blue whale population. Thus, modifying the surplus‐yield model to include iron defecation indicates that blue whales do not render marine resources unavailable to fisheries. By defecating iron‐rich feces, blue whales promote Southern Ocean productivity, rather than reducing fishery yields.     

Empirical power and sample size calculations for cluster-randomized and cluster-randomized crossover studies

In recent years, the number of studies using a cluster-randomized design has grown dramatically. In addition, the cluster-randomized crossover design has been touted as a methodological advance that can increase efficiency of cluster-randomized studies in certain situations. While the cluster-randomized crossover trial has become a popular tool, standards of design, analysis, reporting and implementation have not been established for this emergent design. We address one particular aspect of cluster-randomized and cluster-randomized crossover trial design: estimating statistical power. We present a general framework for estimating power via simulation in cluster-randomized studies with or without one or more crossover periods. We have implemented this framework in the clusterPower software package for R, freely available online from the Comprehensive R Archive Network. Our simulation framework is easy to implement and users may customize the methods used for data analysis. We give four examples of using the software in practice. The clusterPower package could play an important role in the design of future cluster-randomized and cluster-randomized crossover studies. This work is the first to establish a universal method for calculating power for both cluster-randomized and cluster-randomized clinical trials. More research is needed to develop standardized and recommended methodology for cluster-randomized crossover studies.     

The proteomes of human parotid and submandibular/sublingual gland salivas collected as the ductal secretions

Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications--914 in parotid and 917 in submandibular/sublingual saliva--were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets.     

Mind the Gap: Genetic Manipulation of Basicranial Growth within Synchondroses Modulates Calvarial and Facial Shape in Mice through Epigenetic Interactions

Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual locus upon which a particular selective pressure is acting. Phenotypic changes observed over the course of evolution may not all require adaptationist explanations; rather, it is likely that a substantial portion of observed phenotypic variation over the history of a clade is not directly adaptive but rather a secondary consequence of some local response to selection.     

Passive immunotherapy in advanced HIV infection and therapeutic plasmapheresis in asymptomatic HIV-positive individuals: a four-year clinical experience

We have been treating patients with advanced HIV disease using passiveimmunotherapy (PIT). Earlier studies of PIT which have been publishedconcerned relatively short periods of treatment: our study is by far the longest and reports also on the long-term effects of plasmapheresis onhealthy HIV-infected individuals. Fifty-nine patients with an average CD4+T-cell count of 55 per cu.mm. at baseline were transfused at monthlyintervals with 500 ml of hyperimmune plasma. No disease progression ordeath occurred among the 8 asymptomatic patients under the treatment, whichlasted for 36.25 months on average. Seven of the 15 ARC patients progressedto AIDS but none died in an average period of 25.9 months. Seven of the 36symptomatic AIDS patients with advanced disease died in an average period of19.6 months. PIT appears to be nontoxic and to have beneficial effectslasting at least four years under continuous treatment. It probably delaysdisease progression in ARC and AIDS patients, and almost certainly does soin asymptomatic late HIV infection with a very low CD4+ T-cell count. Noneof the 51 donors suffered adverse effects, nor did any progress to ARC orAIDS in an average period of 30.1 months. Their laboratory parametersindicated a nearly stable condition: in particular, their average CD4+T-cell count rose from 478 to 498. The study of our plasma donors indicatedthat repeated and frequent plasma donation by asymptomatic HIV-infectedindividuals could delay disease progression, although further studies areneeded to investigate this.