Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial.

BACKGROUND: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). METHODS: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. RESULTS: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). CONCLUSION: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

The development of a theory informed behaviour change intervention to improve adherence to dietary and physical activity treatment guidelines in individuals with familial hypercholesterolaemia (FH).

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic condition characterised by elevated levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of cardiovascular disease (CVD). Following dietary and physical activity guidelines could help minimise this risk but adherence is low. Interventions to target these behaviours are therefore required. A comprehensive understanding of the target behaviours and behaviour change theory should drive the process of intervention development to increase intervention effectiveness and scalability. This paper describes the application of a theoretical framework to the findings of a qualitative evidence synthesis (QES) to inform the content and delivery of an intervention to improve adherence to dietary and physical activity guidelines in individuals with FH. METHODS: The Behaviour Change Wheel (BCW) was used to guide intervention development. Factors influencing dietary and physical activity behaviours were identified from an earlier QES and mapped onto factors within the BCW. A comprehensive behavioural diagnosis of these factors was conducted through application of the theoretical domains framework (TDF). Using these data, the most appropriate intervention functions and behaviour change techniques (BCTs) for inclusion in the intervention were identified. Decision making was guided by evaluation criteria recommended by BCW guidance and feedback from individuals with FH. RESULTS: Factors influencing dietary and physical activity behaviours mapped onto twelve of the fourteen TDF domains, with seven intervention functions deemed suitable to target the domains' theoretical constructs. Twenty-six BCTs were identified as being appropriate for delivery within these functions and were included in the intervention. For instance, within the enablement intervention function, the BCT problem solving was incorporated by inclusion of a 'barriers and solutions' section. Guided by evaluation criteria and feedback from individuals with FH, the intervention will be delivered as an hour-long family-based appointment, followed up with four telephone calls. CONCLUSIONS: The novel application of the BCW and TDF to the results of a QES has enabled the development of a theory and evidence informed behaviour change intervention. This systematic approach facilitates evaluation of the intervention as part of an ongoing feasibility trial. The transparent approach taken can be used to guide intervention development by researchers in other fields.

Don't go chasing artificial waterfalls: Artificial line limits and cascading failures in power grids.

Research on cascading failures in power-transmission networks requires detailed data on the capacity of individual transmission lines. However, these data are often unavailable to researchers. Consequently, line limits are often modeled by assuming that they are proportional to some average load. However, there is scarce research to support this assumption as being realistic. In this paper, we analyze the proportional loading (PL) approach and compare it to two linear models that use voltage and initial power flow as variables and are trained on the line limits of a real power network that we have access to. We compare these artificial line-limit methods using four tests: the ability to model true line limits, the damage done during an attack, the order in which edges are lost, and accuracy ranking the relative performance of different attack strategies. We find that the linear models are the top-performing method or are close to the top in all the tests we perform. In comparison, the tolerance value that produces the best PL limits changes depending on the test. The PL approach was a particularly poor fit when the line tolerance was less than two, which is the most commonly used value range in cascading failure research. We also find indications that the accuracy of modeling line limits does not indicate how well a model will represent grid collapse. The findings of this paper provide an understanding of the weaknesses of the PL approach and offer an alternative method of line-limit modeling.

Successful embolisation of pelvic fistulating vessels to the prostate arising after TURP - a rare cause of postoperative bleeding.

Transurethral resection of the prostate (TURP) is considered the gold-standard operation to treat lower urinary tract symptoms due to benign prostatic enlargement in men. Postoperative bleeding is a recognised complication and managing it is a core skill required by attending urologists. We report a rare case of postoperative bleeding caused by fistulating vessels to the prostate which developed after TURP. These fistulas arose from the right internal iliac vessels and communicated with pre-existing pelvic varices affecting the right paraprostaticand seminal vesicle tissues. The fistulating vessels were successfully embolised with liquid embolic agent. Surgeons should be aware that persisting haemorrhage can occur post-TURP from the rare presence of fistulating vessels communicating with pelvic varices. Early computed tomography angiographic assessment is warranted in cases where bleeding is prolonged and refractory to standard management in view of timely referral for percutaneous embolisation.

GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex.

We have examined the role of ras-related rab proteins in transport from the ER to the Golgi complex in vivo using a vaccinia recombinant T7 RNA polymerase virus to express site-directed rab mutants. These mutations are within highly conserved domains involved in guanine nucleotide binding and hydrolysis found in ras and all members of the ras superfamily. Substitutions in the GTP-binding domains of rab1a and rab1b (equivalent to the ras 17N and 116I mutants) resulted in proteins which were potent trans dominant inhibitors of vesicular stomatitis virus glycoprotein (VSV-G protein) transport between the ER and cis Golgi complex. Immunofluorescence analysis indicated that expression of rab1b121I prevented delivery of VSV-G protein to the Golgi stack, which resulted in VSV-G protein accumulation in pre-Golgi punctate structures. Mutants in guanine nucleotide exchange or hydrolysis of the rab2 protein were also strong trans dominant transport inhibitors. Analogous mutations in rab3a, rab5, rab6, and H-ras did not inhibit processing of VSV-G to the complex, sialic acid containing form diagnostic of transport to the trans Golgi compartment. We suggest that at least three members of the rab family (rab1a, rab1b, and rab2) use GTP hydrolysis to regulate components of the transport machinery involved in vesicle traffic between early compartments of the secretory pathway.

Rab1b regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.

We report an essential role for the ras-related small GTP-binding protein rab1b in vesicular transport in mammalian cells. mAbs detect rab1b in both the ER and Golgi compartments. Using an assay which reconstitutes transport between the ER and the cis-Golgi compartment, we find that rab1b is required during an initial step in export of protein from the ER. In addition, it is also required for transport of protein between successive cis- and medial-Golgi compartments. We suggest that rab1b may provide a common link between upstream and downstream components of the vesicular fission and fusion machinery functioning in early compartments of the secretory pathway.

ECOLOGY: Louisiana's Vanishing Wetlands: Going, Going ...

An ambitious $14 billion plan known as Coast 2050 attempts to protect more than 10,000 square kilometers of Louisiana's wetlands, which are disappearing at a rate of up to 90 square kilometers per year, one of the highest rates of land loss in the world. But a number of unanswered scientific questions swirl around the plan. And it could run afoul of powerful interests in the shipping, petroleum, and fishing industries.

The rat temporal association cortical area 2 (Te2) comprises two subdivisions that are visually responsive and develop independently.

In this study, we have used the expression of non-phosphorylated neurofilament (NNF), a protein that exhibits differential areal and laminar neuronal patterning, to assess the chemoarchitectural organization of the rat temporal association cortex (Te). Since expression of NNF is associated with the latter stages of neuronal development, this enabled us to profile the hierarchical development of this region of the cortex. We also examined the expression of the protein Fos, the product of the immediate-early gene cFos, as a neuronal activity marker to determine which areas within this region are visually responsive. Our findings reveal the existence of two previously undescribed subdivisions within the dorsal and ventral domains of the rat temporal association cortical area 2 (Te2) which we have termed Te2d and Te2v, respectively. We also demonstrated the early maturation of the caudal region of Te2d while preceding the primary visual cortex. Within this region of the cortex, the Fos protein indicates that both subdivisions are visually responsive.

No evidence of Mycobacterium avium subsp. paratuberculosis in in vitro produced cryopreserved embryos derived from subclinically infected cows.

The aim of the project was to ascertain if Mycobacterium avium subsp. paratuberculosis (Map) could be cultured from frozen-thawed in vitro produced (IVP) embryos derived from cows with subclinical Johne's disease (JD). Straws of 109 IVP embryos were obtained from 267 cumulus-oocyte-complexes (COCs) collected from 12 clinically normal cows in which antibodies against Map were detected in blood by an enzyme-linked immunosorbent assay (ELISA). These embryos were processed, washed using the standard protocol as described by the International Embryo Transfer Society (IETS) and frozen in a commercial IVP embryo laboratory. Of the 12 donor cows, 11 had histopathological or bacteriological evidence of infection at post-mortem inspection. The frozen embryos were thawed and the contents of the straws were cultured using the radiometric mycobacterial culture method. No Map was detected in any of the 109 embryos or freezing media. This suggests that the use of in vitro produced and cryopreserved embryos derived from cows with subclinical JD poses very low, if any, risk of spreading infection to susceptible animals.

The temporal profile of retinal cell genesis in the marmoset monkey.

The New World marmoset monkey (Callithrix jacchus) has a relatively short gestational period compared with other primates but possesses a retina at a similar stage of maturation by birth. Previous studies have highlighted that the complex fovea of the marmoset undergoes a more rapid postnatal development in comparison with the Macaca monkey, reaching a mature stage earlier than these species. In this current study, we examined the prenatal proliferation profile of cells in the entire retina employing the thymidine analogs and also determined their phenotype by double-label immunocytochemistry using type-specific markers. Akin to other primate species, we demonstrate a centroperipheral gradient in the emergence of both neurons and Müller glia with cones, ganglion cells, and horizontal cells generated first in the fovea at fetal day (Fd)70-74 and with the last generated at the retinal edge at Fd115. Rods, bipolar cells, amacrine cells, displaced amacrine cells, and Müller glia were generated between Fd76 and Fd135 along the same gradient. Similar to foveal development, marmoset neuronal generation was rapid, only taking 51% of gestation whereas in Macaca this takes 81%.

Protocolised approach to end-of-life care in the ICU--the ICU PALCare Pilot Project.

International literature on end-of-life care in intensive care units (ICUs) supports the use of 'protocol bundles', which is not common practice in our 18-bed adult general ICU in Sydney, New South Wales. We conducted a prospective observational study to identify problems related to end-of-life care practices and to determine whether there was a need to develop protocol bundles. Any ICU patient who had 'withdrawal' of life-sustaining treatment to facilitate a comfortable death was eligible. Exclusion criteria included organ donors, unsuitable family dynamics and lack of availability of research staff to obtain family consent. Process-of-care measures were collected using a standardised form. Satisfaction ratings were obtained using de-identified questionnaire surveys given to the healthcare staff shortly after the withdrawal of therapy and to the families 30 days later. Twenty-three patients were enrolled between June 2011 and July 2012. Survey questionnaires were given to 25 family members and 30 healthcare staff, with a high completion rate (24 family members [96%] and 28 staff [93.3%]). Problems identified included poor documentation of family meetings (39%) and symptom management. Emotional/spiritual support was not offered to families (39.1%) or ICU staff (0%). The overall level of end-of-life care was good. The overwhelming majority of families and healthcare staff were highly satisfied with the care provided. Problems identified related to communication documentation and lack of spiritual/emotional support. To address these problems, targeted measures would be more useful than the adoption of protocol bundles. Alternate models of satisfaction surveys may be needed.

Retrograde transneuronal degeneration in the retina and lateral geniculate nucleus of the V1-lesioned marmoset monkey.

Retrograde transneuronal degeneration (RTD) of retinal ganglion cells and dorsal lateral geniculate (LGN) neurons are well described following a lesion of the primary visual cortex (V1) in both Old World monkeys and humans. Based on previous studies of New World monkeys and prosimians, it was suggested that these species displayed no RTD following a lesion of V1. In this study of the New World marmoset monkey, 1 year after a unilateral V1 lesion either in adults or at 14 days after birth, we observed ~20 % ganglion cell (GC) loss in adult but ~70 % in infants. This finding is similar to the RTD previously described for Old World Macaca monkeys. Furthermore, in infants we find a similar amount of RTD at 3 weeks and 1 year following lesion, demonstrating that RTD is very rapid in neonates. This highlights the importance of trying to prevent the rapid onset of RTD following a lesion of V1 in early life as a strategy for improved functional recovery. Despite differences in GC loss, there was little difference between LGN degeneration in infant versus adult lesions. A wedge on the horizontal meridian corresponding to the LGN foveal representation revealed extensive neuronal loss. Retinal afferent input was labeled by cholera toxin B subunit. Input to the degenerated parvocellular layers was difficult to detect, while input to magnocellular and koniocellular layers was reduced but still apparent. Our demonstration that the New World marmoset monkey shares many of the features of neuroplasticity with Old World Macaca monkeys and humans emphasizes the opportunity and benefit of marmosets as models of visual cortical injury.

SCH 23390 affords protection against soman-evoked seizures in the freely moving guinea-pig: a concomitant neurochemical, electrophysiological and behavioural study.

We studied the role of striatal dopamine (DA) release in seizure activity evoked by the subcutaneous administration of the cholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman), in the guinea-pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the D(1)-like receptor antagonist SCH 23390 (0.5 mg kg(-1)) or the D(2)-like receptor antagonist sulpiride (30 mg kg(-1)). Microdialysis and HPLC with electrochemical detection were used to monitor changes in extracellular levels of striatal DA and its metabolites, acetylcholine and choline. These data were correlated with changes in the striatal and cortical electroencephalogram and observation of predefined clinical signs. We found that the blockade of the D(1) receptor with SCH 23390 can inhibit seizure activity, while blockade of the D(2) receptor with sulpiride can augment the evoked seizure activity. These results clarify the involvement of the dopaminergic system in soman-evoked seizures.

The Vanderbilt University fast track to IAIMS: transition from planning to implementation.

Vanderbilt University Medical Center is implementing an Integrated Advanced Information Management System (IAIMS) using a fast-track approach. The elapsed time between start-up and completion of implementation will be 7.5 years. The Start-Up and Planning phases of the project are complete. The Implementation phase asks one question: How does an organization create an environment that redirects and coordinates a variety of individual activities so that they come together to provide an IAIMS? Four answers to this question are being tested. First, design resources to be "scalable"--i.e., capable of supporting enterprise-wide use. Second, provide information technology planning activities as ongoing core functions that direct local efforts. Third, design core infrastructure resources to be both reusable and expandable at the local level. Fourth, use milestones to measure progress toward selected endpoints to permit early refinement of plans and strategies.

Radiographic evidence of interstitial pulmonary edema after exercise at altitude.

Pulmonary function abnormalities after exercise are suggestive of pulmonary edema; however, radiographic evidence is lacking. Well-trained cyclists were studied to determine whether there is radiographic evidence of pulmonary edema after endurance exercise (cycling distance 5.3-131.5 km) at altitude. Chest radiographs obtained before exercise were coded for later interpretation. Films obtained after exercise were coded with a different number. A total of 74 sets of posteroanterior and lateral films were analyzed by three radiologists for signs of pulmonary edema. Radiographic changes were graded on a three-point scale. An edema score was calculated by summing the score for each individual radiographic finding for each radiologist and an overall edema score representing the mean scores from all three radiologists. The overall edema score increased from 0.8 +/- 1.2 before exercise to 1.8 +/- 1.6 after exercise (P < 0.01). These results suggest that, after prolonged high-intensity exercise at moderate altitude, there is radiographic evidence of early pulmonary edema in some cyclists.

Neurotoxicity in uremia.

The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms which may be impaired in the abnormal chemical environment imposed in renal failure. It is the behaviors we comprehend as indicators of disordered nervous mechanisms. Therefore, it is logical that neurophysiological and neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective endpoint measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results illustrate that: 1) measures of conduction velocity, distal latency and response amplitudes, as employed by us, were relatively insensitive in the patients and circumstances studied; 2) several neurophysiological measures, i.e., the spontaneous EEG, VER latency and, perhaps, photic stimulation, on the other hand, are highly correlated with the severity of renal failure; 3) behavioral measures of sustained attention and alertness (TMT), of short-term memory (ASTM) and of cognitive manipulation of symbols (AR) are also highly correlated with the severity of renal failure; 4) some measured abnormalities improve following dialysis, but not always to normal--three residual impairments may indicate dialysis in adequacy; 5) several of these measures can provide objective evidence for adequacy of dialysis and other clinical and treatment effects in patients with renal failure.

Binding and agonist/antagonist actions of M35, galanin(1-13)-bradykinin(2-9)amide chimeric peptide, in Rin m 5F insulinoma cells.

The chimeric peptide M35 [galanin(1-13)-bradykinin(2-9) amide] is a high-affinity galanin receptor ligand acting as a galanin receptor antagonist in the rat spinal cord, rat hippocampus and isolated mouse pancreatic islets. We have radiolabelled M35 and performed equilibrium binding studies with [125I]M35 on the rat pancreatic beta-cell line Rin m 5F, whereby we show the existence of high-affinity binding site (KD = 0.9 +/- 0.1 nM) with a Bmax of 72 +/- 3 fmol/mg protein. Galanin displaces [125I]M35 with the same affinity (KD = 1 nM) as it displaces [125I]galanin. Displacement of [125I]galanin by M35 from Rin m 5F cell membranes shows the presence of two binding sites for M35 with KD-values of 0.3 +/- 0.1 nM and 0.52 +/- 0.03 microM, respectively. The GTP- and pertussis toxin-sensitivity of M35 binding to Rin m 5F membranes shows that binding of [125I]M35 is almost completely abolished by the presence of GTP or after pertussis toxin treatment of the cells, indicating an agonist-like binding of M35 to the galanin receptors. M35 has a dual effect on the galanin mediated inhibition of forskolin stimulated cyclic AMP production in Rin m 5F cells: at low concentrations M35 antagonises the effect of galanin, whereas at concentrations above 10 nM M35 acts as a galanin receptor agonist. These agonist-like effects of galanin and M35 are not additive, thus the mixed agonist/antagonist properties arise from the chimeric nature of M35[galanin(1-13)-bradykinin(2-9)amide] acting solely at galanin receptors.

Novel method of monitoring electroencephalography at the site of microdialysis during chemically evoked seizures in a freely moving animal.

This paper covers the design, development and operation of a novel piece of equipment, based around the CMA/12 guide probe (Carnegie Medicin, Sweden), which offers a low cost alternative for monitoring EEG at the site of microdialysis in a freely moving animal. This equipment is entirely based on commercially available parts, and thus can be easily replicated. Moreover, it is less intrusive than earlier models, offering advantages for experiments in which behavioural testing or chronic monitoring is required. We illustrate its use in a study of changes in electrical seizure activity, in both cortex and basal nuclei, evoked by the administration of the chemoconvulsant soman. The inference from the many experimental paradigms looking at the mechanisms of chemoconvulsants is that paroxysmal discharges are a better correlate of seizure activity than behavioural signs. The correlation of the EEG with extracellular neurotransmitter data, over a period of hours post-injection of chemoconvulsant, allows the determination of whether extracellular neurotransmitter changes are a cause or consequence of the evoked electrical activity.

Changes in striatal electroencephalography and neurochemistry induced by kainic acid seizures are modified by dopamine receptor antagonists.

We investigated the involvement of striatal dopamine release in electrographic and motor seizure activity evoked by kainic acid in the guinea pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the dopamine D(1) receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.5 mg kg(-1)), or the dopamine D(2) antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg(-1)). Microdialysis and high performance liquid chromatography were used to monitor changes in extracellular levels of striatal dopamine and its metabolites, glutamate, aspartate and gamma-amino-butyric acid (GABA). These data were correlated with changes in the striatal and cortical electroencephalographs and clinical signs. We found that, although neither dopamine receptor antagonist inhibited behavioural seizure activity, blockade of the dopamine D(1)-like receptor with SCH 23390 significantly reduced both the 'power' of the electrical seizure activity and the associated change in extracellular striatal concentration of glutamate, whilst increasing the extracellular striatal concentration of GABA. In contrast, blockade of the dopamine D(2)-like receptor with sulpiride significantly increased the extracellular, striatal content of glutamate and the dopamine metabolites. These results confirm previous evidence in other models of chemically-evoked seizures that antagonism of the dopamine D(1) receptor tends to reduce motor and electrographic seizure activity as well as excitatory amino-acid transmitter activity, while antagonism of the dopamine D(2) receptor has relatively less apparent effect.