In a randomized trial involving 4000 patients in the ICU who required sedation for mechanical ventilation, dexmedetomidine had no benefit on 90-day mortality as compared with usual care and was ...associated with more adverse events. Additional drugs were required for prescribed sedation levels in the two groups.
Background
There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel (SBTT), colon (CTT) and whole gut transit (WGTT) times are conveniently ...obtained by SmartPill® wireless motility capsule (WMC) that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (MotiliGI®) were investigated for diagnostic application. GET and SBTT were separately measured using video capsule endoscopy (VCE). The aim of this investigation was to assess same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam® SB (small bowel) VCE motility data.
Methods
Seventy three healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT. Nineteen subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted.
Key Results
Visually derived data from WMC yielded GET 3.46±0.27, SBTT 5.15±0.21, CTT 20.76±1.19 and WGTT 29.53±1.28 hours (mean±SEM). Pearson's correlation coefficients (r) against software derived results were: GET 0.78 (P<.0001), SBTT 0.28 (P<.05), CTT 0.96 (P<.0001), WGTT 0.99 (P<.0001). VCE yielded lower GET (0.71±0.08 hours) and SBTT (4.15±0.13 hours).
Conclusions and Inferences
GET, SBTT, CTT and WGTT obtained by WMC are commensurate with literature values, including by other methods. Visually and software derived transit times have strongest correlations for CTT and WGTT. WMC yields longer GET and SBTT than VCE, perhaps due to meal related effects on motility.
Gastric emptying time and small bowel transit time for SmartPill® WMC (mixed meal) and Pillcam® SB VCE (fasted) (mean +/‐ SEM).
Background
Ghrelin has been shown to stimulate gastric emptying in healthy humans and patients with delayed gastric emptying. The aim of this study is to assess the effect of ghrelin on gastric ...emptying on day 2 after open colorectal surgery.
Methods
Twenty‐four patients (mean age 69.2 ± 1.4, BMI 25.8 ± 0.8 kg m−2) were randomized to saline or ghrelin infusion (15 pmol kg−1 min−1) during 3 h before and on day 2 after open colorectal surgery. Of these, 20 were assessed both before and after surgery. At start of infusion, a liquid meal (480 kcal, 200 mL) was administered together with 1.5 g acetaminophen. Plasma was obtained at regular intervals together with visual analogue scales for hunger, satiety and nausea. Acetaminophen was analyzed as a marker of gastric emptying. Plasma glucose, insulin, acyl‐ghrelin, glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinoptrophic peptide (GIP), pancreatic polypeptide and peptide YY (PYY) were analyzed.
Key Results
Gastric emptying was faster during ghrelin infusion compared to saline before and after surgery (P < 0.02). In addition, plasma glucose was increased (P < 0.05). With ghrelin infusion, plasma insulin was unchanged except for lower values postoperatively (P < 0.05). Ghrelin did not alter plasma concentrations of gut peptides. After surgery, ghrelin shortened the time to first bowel movement compared to saline (2.1 ± 0.3 vs 3.5 ± 0.4 days, P = 0.02).
Conclusions & Inferences
A 3‐h ghrelin infusion increased the gastric emptying rate and hastened the time to first bowel movement after surgery. Ghrelin/ghrelin receptor agonists have a therapeutic potential in postoperative ileus; Karolinska Clinical Trial Registry nr CT20110084.
Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited.
...We pooled individual-level data from seven cohort and five case–control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect.
At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 95% CI 0.76–0.98 and 0.86 95% CI 0.76–0.97, respectively, for aspirin; 0.87 95% CI 0.76–1.00 and 0.84 0.74–0.96, respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2–6 times/week (OR = 0.81, 95% CI 0.68–0.96) than for daily use (0.91, 0.80–1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen.
Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.
Cloud feedbacks are the leading cause of uncertainty in climate sensitivity. The complex coupling between clouds and the large‐scale circulation in the tropics contributes to this uncertainty. To ...address this problem, the coupling between clouds and circulation in the latest generation of climate models is compared to observations. Significant biases are identified in the models. The implications of these biases are assessed by combining observations of the present day with future changes predicted by models to calculate observationally constrained feedbacks. For the dynamic cloud feedback (i.e., due to changes in circulation), the observationally constrained values are consistently larger than the model‐only values. This is due to models failing to capture a nonlinear minimum in cloud brightness for weakly descending regimes. Consequently, while the models consistently predict that these regimes increase in frequency in association with a weakening tropical circulation, they underestimate the positive cloud feedback associated with this increase.
Plain Language Summary
Climate models are crucial for understanding the impacts of climate change. Yet there are significant differences between models even for the global mean temperature increase due to a doubling of carbon dioxide concentrations (known as the climate sensitivity). These differences in climate sensitivity are largely due to differences in cloud responses to warming between the models (known as cloud feedbacks). Cloud feedback uncertainty is particularly large for tropical clouds. One reason for this is the two‐way interactions between clouds and the large‐scale circulation. This remains relatively poorly understood and involves processes that occur at a wide range of scales which cannot be captured by climate models. This study examines relationships between clouds and circulation in the tropics in the latest generation of climate models. Cloud feedbacks can be separated into dynamic (changes in circulation) and thermodynamic (changes in cloud for a given circulation regime) components. We use this framework to calculate the cloud feedbacks models would predict if the relationships between clouds and circulation matched observations. This results in an increase in the dynamic component of the cloud feedback which is due to the models' failure to capture the observed nonlinear relationships between clouds and circulation.
Key Points
Climate models miss key details of the observed links between tropical clouds and circulation, notably for common weak subsidence regimes
Using observations to constrain thermodynamic and dynamic cloud feedbacks in models increases the dynamic and hence total feedback
This is due to subtle nonlinear changes in the observed SW cloud radiative effect across circulation regimes that the models predict will change in frequency
Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are ...sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Biogenic dimethylsulfide (DMS) is a significant contributor to sulfur flux from the oceans to the atmosphere, and the most significant source of aerosol non sea-salt sulfate (NSS-SO
), a key ...regulator of global climate. Here we present the longest running time-series of DMS-water (DMS
) concentrations in the world, obtained at the Rothera Time-Series (RaTS) station in Ryder Bay, West Antarctic Peninsula (WAP). We demonstrate the first ever evaluation of interseasonal and interannual variability in DMS
and associated flux to the atmosphere from the Antarctic coastal zone and determine the scale and importance of the region as a significant source of DMS. Impacts of climate modes such as El Niňo/Southern Oscillation are evaluated. Maximum DMS
concentrations occurred annually in January and were primarily associated with sea-ice break-up. These concentrations resulted in extremely high (up to 968 µmol m
d
) DMS flux over short timescales, which are not parameterised in global-scale DMS climatologies. Calculated DMS flux stayed above the aerosol nucleation threshold of 2.5 µmol m
d
for 60% of the year. Overall, using flux determinations from this study, the total flux of DMS-sulfur from the Austral Polar Province (APLR) was 1.1 Tg sulfur yr
, more than double the figure suggested by the most recent DMS climatologies.
AIMS: Three soils that varied in their physicochemical characteristics and microbial diversity were inoculated with Escherichia coli O157:H7 and Salmonella to determine the relative impact of abiotic ...and biotic factors on the pathogens' survival when the soil was held at 25°C. METHODS AND RESULTS: Three soils that were classified as having low, medium and high microbial diversity were divided into two batches for adjustment to 20% of water‐holding capacity and to 40% of water‐holding capacity. Soils were inoculated with both green fluorescent‐labelled E. coli O157:H7 and red fluorescent‐labelled Salmonella (5 log CFU g⁻¹dry weight) and held at 25°C. Pathogens inoculated into an acidic soil died off within 9 weeks, whereas they were still detected in the other two soils by enrichment culture after 18 weeks. Moisture did not affect inactivation of E. coli O157:H7, but did affect Salmonella inactivation in soil having the greatest organic load and microbial diversity. Using multiple linear regression analysis, 98·7% of the variability in the inactivation rate for E. coli O157:H7 was explained by a model that included the variables of initial pH and electrical conductivity. Salmonella's inactivation rate was predicted by a model that included pH and initial cell numbers of copiotrophic and oligotrophic bacteria. CONCLUSION: This study provided evidence of specific properties that impact inactivation of E. coli O157:H7 and Salmonella in soils at 25°C. SIGNIFICANCE AND IMPACT OF THE STUDY: Identification of factors influential in the die‐off of enteric pathogens will assist in developing guidelines for safe intervals between field contamination events and planting or harvesting of fresh‐cut produce crops.
Purpose
Anterior lumbar surgery is a common procedure for anterior lumbar interbody fusion (ALIF) and artificial disc replacement (ADR). Our aim was to study the exposure related complications for ...anterior lumbar spinal surgery performed by spinal surgeons.
Methods
A retrospective review was performed for 304 consecutive patients who underwent anterior lumbar spinal surgery over 10 years (2001–2010) at our institution. Each patient’s records were reviewed for patients’ demographics, diagnosis, level(s) of surgery, procedure and complications related to access surgery. Patients undergoing anterior lumbar access for tumour resection, infection, trauma and revision surgeries were excluded.
Results
All patients underwent an anterior paramedian retroperitoneal approach from the left side. The mean age of patients was 43 years (10–73; 197 males, 107 females). Indications for surgery were degenerative disc disease (DDD 255), degenerative spondylolisthesis (23), scoliosis (18), iatrogenic spondylolisthesis (5) and pseudoarthrosis (3). The procedures performed were single level surgery—L5/S1 (
n
= 147), L4/5 (
n
= 62), L3/4 (
n
= 7); two levels—L4/5 and L5/S1 (
n
= 74), L3/4 and L4/5 (
n
= 4); three levels—L3/4, L4/5, L5/S1 (
n
= 5); four levels—L2/3, L3/4, L4/5, L5/S1 (
n
= 5). The operative procedures were single level ADR (
n
= 131), a single level ALIF (
n
=
87) with or without posterior fusion, two levels ALIF (
n
= 54), two levels ADR (
n
= 14), a combination of ADR/ALIF (
n
= 10), three levels ALIF (
n
= 1), three levels ADR/ALIF/ALIF (
n
= 1), ADR/ADR/ALIF (
n
= 2), four levels ALIF (
n
= 1) and finally 3 patients underwent a four level ADR/ADR/ALIF/ALIF. The overall complication rate was 61/304 (20 %). This included major complications (6.2 %)—venous injury requiring suture repair (
n
= 14, 4.6 %) and arterial injury (
n
= 5 1.6 %, 3 repaired, 2 thrombolysed). Minor complications (13.8 %) included venous injury managed without repair (
n
= 5, 1.6 %), infection (
n
= 13, 4.3 %), incidental peritoneal opening (
n
= 12, 3.9 %), leg oedema (
n
= 2, 0.6 %) and others (
n
= 10, 3.3 %). We had no cases of retrograde ejaculation.
Conclusion
We report a very thorough and critical review of our anterior lumbar access surgeries performed mostly for DDD and spondylolisthesis at L4/5 and L5/S1 levels. Vascular problems of any type (24/304, 7.8 %) were the most common complication during this approach. The incidence of major venous injury requiring repair was 14/304 (4.6 %) and arterial injury 5/304 (1.6 %). The requirement for a vascular surgeon with the vascular injury was 9/304 (3 %; 5 arterial injuries; 4 venous injuries). This also suggests that the majority of the major venous injuries were repaired by the spinal surgeon (10/14, 71 %). Our results are comparable to other studies and support the notion that anterior access surgery to the lumbar spine can be performed safely by spinal surgeons. With adequate training, spinal surgeons are capable of performing this approach without direct vascular support, but they should be available if required.
The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug ...targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13348/full. G protein‐coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC‐IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR‐DB and GRAC and provides a permanent, citable, point‐in‐time record that will survive database updates.
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