Aims/hypothesis
Cardiovascular events and death are better predicted by postprandial glucose (PPG) than by fasting blood glucose or HbA
1c
. While chronic exercise reduces HbA
1c
in patients with ...type 2 diabetes, short-term exercise improves measures of insulin sensitivity but does not consistently alter responses to the OGTT. The purpose of this study was to determine whether short-term exercise training improves PPG and glycaemic control in free-living patients with type 2 diabetes, independently of the changes in fitness, adiposity and energy balance often associated with chronic exercise training.
Methods
Using continuous glucose monitors, PPG was quantified in previously sedentary patients with type 2 diabetes not using exogenous insulin (
n
= 13, age 53 ± 2 years, HbA
1c
6.6 ± 0.2% (49.1 ± 1.9 mmol/mol)) during 3 days of habitual activity and during the final 3 days of a 7 day aerobic exercise training programme (7D-EX) which does not elicit measurable changes in cardiorespiratory fitness or body composition. Diet was standardised across monitoring periods, with modifications during 7D-EX to offset increases in energy expenditure. OGTTs were performed on the morning following each monitoring period.
Results
7D-EX attenuated PPG (
p
< 0.05) as well as the frequency, magnitude and duration of glycaemic excursions (
p
< 0.05). Conversely, average 24 h blood glucose did not change, nor did glucose, insulin or C-peptide responses to the OGTT.
Conclusions/interpretation
7D-EX attenuated glycaemic variability and PPG in free-living patients with type 2 diabetes but did not significantly alter responses to the laboratory-based OGTT. These effects appeared to be independent of changes in fitness, body composition or energy balance.
ClinicalTrials.gov numbers:
NCT00954109 and NCT00972452.
Funding:
This project was funded by the University of Missouri Institute for Clinical and Translational Sciences (CRM), NIH grant T32 AR-048523 (CRM), Diabetes Action Research and Education Foundation (JPT). Medtronic supplied CGMS sensors at a discounted rate.
Viva la VOSCE? Boyle, J G; Colquhoun, I; Noonan, Z ...
BMC medical education,
12/2020, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The COVID-19 pandemic lockdown precluded face-to-face final Objective Structured Clinical Examinations (OSCE) in the UK.
In response, we rapidly developed and then successfully implemented a novel ...Virtual Objective Structured Clinical Examination (VOSCE).
In this article we both describe and reflect on our experience as well as discuss the implications for future undergraduate assessment as the situation evolves.
To determine short-term outcomes of infants with evidence of hypoxia-ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age.
Prospective multicenter study. Mild NE was ...defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge.
A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing.
A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.
Abstract We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the ...first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 10 51 –10 57 erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB.
We examined the in vivo growth, dissemination, and reactivation of strains of the protozoan parasite Toxoplasma gondii using a bioluminescence-based imaging system. Two T. gondii strains, one with a ...highly virulent disease phenotype in mice (S23) and the other with a 1,000-fold-lower virulence phenotype (S22), were engineered to stably express the light-emitting protein luciferase. One clone of each wild-type strain was isolated, and the two clones (S23-luc7 and S22-luc2) were found to express similar levels of luciferase. Mice were infected intraperitoneally with S23-luc7 (50 or 5 parasites) or S22-luc2 (500, 50, or 5 parasites), and the progress of the infections was examined noninvasively following injection of the substrate for luciferase, D-luciferin. In mice infected with 50 S23-luc7 parasites, the parasites grew exponentially within the peritoneal cavity (as measured by light emitted from luciferase-expressing parasites) during days 1 to 10 p.i., and this proliferation continued until there was severe disease. In mice infected with 500 S22-luc2 parasites, the parasites proliferated in a fashion similar to the S23-luc7 proliferation during days 1 to 6, but this was followed by a precipitous drop in the signal to levels below the limit of detection. Using this technique, we were also able to observe the process of reactivation of T. gondii in chronically infected mice. After treatment with dexamethasone, we detected reactivation of toxoplasmosis in mice infected with S23-luc7 and S22-luc2. During reactivation, growth of S23-luc7 was initially detected primarily in the head and neck area, while in S22-luc2-infected mice the parasites were detected primarily in the abdomen. This method has great potential for identifying important differences in the dissemination and growth of different T. gondii strains, especially strains with dramatically different disease outcomes.
Abstract
The CHIME/FRB Project has recently released its first catalog of fast radio bursts (FRBs), containing 492 unique sources. We present results from angular cross-correlations of CHIME/FRB ...sources with galaxy catalogs. We find a statistically significant (
p
-value ∼ 10
−4
, accounting for look-elsewhere factors) cross-correlation between CHIME FRBs and galaxies in the redshift range 0.3 ≲
z
≲ 0.5, in three photometric galaxy surveys: WISE × SCOS, DESI-BGS, and DESI-LRG. The level of cross-correlation is consistent with an order-one fraction of the CHIME FRBs being in the same dark matter halos as survey galaxies in this redshift range. We find statistical evidence for a population of FRBs with large host dispersion measure (∼400 pc cm
−3
) and show that this can plausibly arise from gas in large halos (
M
∼ 10
14
M
⊙
), for FRBs near the halo center (
r
≲ 100 kpc). These results will improve in future CHIME/FRB catalogs, with more FRBs and better angular resolution.
Toxoplasma gondii is an intracellular protozoan pathogen of humans that can cross the placenta and result in adverse pregnancy outcomes and long-term birth defects. The mechanisms used by T. gondii ...to cross the placenta are unknown, but complex interactions with the host immune response are likely to play a role in dictating infection outcomes during pregnancy. Prior work showed that T. gondii infection dramatically and specifically increases the secretion of the immunomodulatory chemokine CCL22 in human placental cells during infection. Given the important role of this chemokine during pregnancy, we hypothesized that CCL22 induction was driven by a specific T. gondii-secreted effector. Using a combination of bioinformatics and molecular genetics, we have now identified T. gondii GRA28 as the gene product required for CCL22 induction. GRA28 is secreted into the host cell, where it localizes to the nucleus, and deletion of the GRA28 gene results in reduced CCL22 placental cells as well as a human monocyte cell line. The impact of GRA28 on CCL22 production is also conserved in mouse immune and placental cells both
and
. Moreover, parasites lacking GRA28 are impaired in their ability to disseminate throughout the animal, suggesting a link between CCL22 induction and the ability of the parasite to cause disease. Overall, these data demonstrate a clear function for GRA28 in altering the immunomodulatory landscape during infection of both placental and peripheral immune cells and show a clear impact of this immunomodulation on infection outcome.
Toxoplasma gondii is a globally ubiquitous pathogen that can cause severe disease in HIV/AIDS patients and can also cross the placenta and infect the developing fetus. We have found that placental and immune cells infected with T. gondii secrete significant amounts of a chemokine (called CCL22) that is critical for immune tolerance during pregnancy. In order to better understand whether this is a response by the host or a process that is driven by the parasite, we have identified a T. gondii gene that is absolutely required to induce CCL22 production in human cells, indicating that CCL22 production is a process driven almost entirely by the parasite rather than the host. Consistent with its role in immune tolerance, we also found that T. gondii parasites lacking this gene are less able to proliferate and disseminate throughout the host. Taken together, these data illustrate a direct relationship between CCL22 levels in the infected host and a key parasite effector and provide an interesting example of how T. gondii can directly modulate host signaling pathways in order to facilitate its growth and dissemination.
Background
Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective ...randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices.
Methods
We allocated mothers of food‐allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer‐generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi‐Q), without device‐specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events.
Results
We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful – RR 1.00 (95% CI 0.68–1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi‐Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001).
Conclusions
AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio‐prompt device Auvi‐Q.
Flux Calibration of CHIME/FRB Intensity Data Andersen, Bridget C.; Patel, Chitrang; Brar, Charanjot ...
The Astronomical journal,
10/2023, Letnik:
166, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
Fast radio bursts (FRBs) are bright radio transients of microsecond to millisecond duration and unknown extragalactic origin. Central to the mystery of FRBs are their extremely high ...characteristic energies, which surpass the typical energies of other radio transients of similar duration, like Galactic pulsar and magnetar bursts, by orders of magnitude. Calibration of FRB-detecting telescopes for burst flux and fluence determination is crucial for FRB science, as these measurements enable studies of the FRB energy and brightness distribution in comparison to progenitor theories. The Canadian Hydrogen Intensity Mapping Experiment (CHIME) is a radio interferometer of cylindrical design. This design leads to a high FRB detection rate but also leads to challenges for CHIME/FRB flux calibration. This paper presents a comprehensive review of these challenges, as well as the automated flux calibration software pipeline that was developed to calibrate bursts detected in the first CHIME/FRB catalog, consisting of 536 events detected between 2018 July 25 and 2019 July 1. We emphasize that, due to limitations in the localization of CHIME/FRB bursts, flux and fluence measurements produced by this pipeline are best interpreted as lower limits, with uncertainties on the limiting value.
Abstract Objectives Aortoiliac aneurysms comprise up to 43% of the specialist endovascular caseload. In such cases endovascular aneurysm repair (EVAR) requires distal extension of the aortoiliac ...endograft beyond the ostium of the internal iliac artery (IIA) and into the external iliac artery, conventionally necessitating the embolisation of one or both IIA. This has been associated with a wide range of complications, and the use of an Iliac Branch-graft Device (IBD) offers an appealing endovascular solution. Design Medline, trial registries, conference proceedings and article reference lists were searched to identify case series reporting IBD use. Data were extracted for review. Results Nine series have reported the use of IBD in a total of 196 patients. Technical success was 85–100%. Median operating times were 101–290 min and median contrast dose was 58–208 g, with no aneurysm-related mortality. Claudication developed in 12/24 patients after IBD occlusion. One type I endoleak and two type III endoleaks occurred and were managed endovascularly. Re-occlusion occurred in 24/196 patients. Conclusion IBD was performed with high technical success rates and encouraging mid-term patency. Formalised risk stratification and morphological data are required to identify the group of patients who will benefit most. Cost-effectiveness appraisals are needed for this technique.
PDF
