Scorpion toxin peptide action at the ion channel subunit level

This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling

Does gated beam delivery impact delivery accuracy on an Elekta linac?

In this study, we evaluated the performance of an Elekta linac in the delivery of gated radiotherapy. Delivery accuracy was examined with an emphasis on the impact of using short gating windows (low monitor unit beam-on segments) or long beam hold times. The performance was assessed using a 20cm by 20cm open field with the radiation delivered using a range of beam-on and beam-off time periods. Gated delivery measurements were also performed for two SBRT plans delivered using volumetric modulated arc therapy (VMAT). Tests included both free-breathing based gating (covering a variety of gating windows) and simulated breath-hold based gating. An IBA MatriXX 2D ion chamber array was used for data collection, and the gating accuracy at low MU was evaluated using gamma passing rates. For the 20 cm by 20 cm open field, the measurements generally showed close agreement between the gated and non-gated beam deliveries. Discrepancies, however, began to appear with a 5-to-1 ratio of the beam-off to beam-on times. The discrepancies observed for these tight gating windows can be attributed to the small number of monitor units delivered during each beam-on segment. Dose distribution analysis from the delivery of the two SBRT plans showed gamma passing rates (± 1%, 2%/1 mm) in the range of 95% to 100% for gating windows of 25%, 38%, 50%, 63%, 75%, and 83%. Using a simulated sinusoidal breathing signal with a 4 second period, the gamma passing rate of free-breathing gating and breath-hold gating deliveries were measured in the range of 95.7% to 100%. In conclusion, the results demonstrate that Elekta linacs can accurately deliver respiratory gated treatments for both free-breathing and breath-hold patients. Some caution should be exercised with the use of very tight gating windows

Risk factors and outcome differences in hypoglycaemia-related hospital admissions: a case-control study in England

Aims: To evaluate risk factors for hospital admissions for hypoglycaemia and compare length of hospitalization, inpatient mortality and hospital readmission between hypoglycaemia- and nonhypoglycaemia-related admissions. Materials and methods: We used all admissions for hypoglycaemia in individuals with diabetes to English NHS hospital trusts between 2005 and 2014 (101 475 case admissions) and 3 random admissions per case in individuals with diabetes without hypoglycaemia (304 425 control admissions). Risk factors and differences in the 3 outcomes were estimated with logistic and negative binomial regressions. Results: A U-shaped relationship between age and risk of admission for hypoglycaemia was observed until the age of 85 years; compared to the nadir at 60 years, the risk was progressively higher in younger and older patients and steadily declined after 85 years. Social deprivation (positively) and comorbidities (negatively) were associated with the risk of admission for hypoglycaemia. Compared to Caucasians, other ethnic groups had lower (Bangladeshi, Pakistani,Indians) or higher (Caribbean) risk of admission for hypoglycaemia. Length of hospitalization was 26% shorter while risk of rehospitalization was 65% higher in individuals admitted for hypoglycaemia. Compared to admissions for hypoglycaemia, risk of inpatient mortality was 50% lower for unstable angina but higher for acute myocardial infarction (3 times), acute renal failure (5 times) or pneumonia (8 times). Conclusions: Among hospital-admitted individuals with diabetes, age, social deprivation, comorbidities and ethnicity are associated with higher frequency of hospitalization for hypoglycaemia. Admission for hypoglycaemia is associated with a greater risk of readmission, a shorter length of hospitalisation and a generally lower inpatient mortality compared to admissions for other medical conditions. These results could help in identifying at-risk groups to reduce the burden of hospitalization for hypoglycaemia

Trends in hospital admissions for hypoglycaemia in England: a retrospective, observational study

BackgroundStudies in the USA and Canada have reported increasing or stable rates of hospital admissions for hypoglycaemia. Some data from small studies are available for other countries. We aimed to gather information about long-term trends in hospital admission for hypoglycaemia and subsequent outcomes in England to help widen understanding for the global burden of hospitalisation for hypoglycaemia.MethodsWe collected data for all hospital admissions listing hypoglycaemia as primary reason of admission between Jan 1, 2005, and Dec 31, 2014, using the Hospital Episode Statistics database, which contains details of all admissions to English National Health Service (NHS) hospital trusts. We calculated trends in crude and adjusted (for age, sex, ethnic group, social deprivation, and Charlson comorbidity score) admissions for hypoglycaemia; in admissions for hypoglycaemia per total hospital admissions and per diabetes prevalence in England; and in length of stay, in-hospital mortality, and 1 month readmissions for hypoglycaemia.Findings79 172 people had 101 475 admissions for hypoglycaemia between 2005 and 2014, of which 72 568 (72%) occurred in people aged 60 years or older. 13 924 (18%) people had more than one admission for hypoglycaemia during the study period. The number of admissions increased steadily from 7868 in 2005, to 11 756 in 2010 (49% increase) and then remained more stable until 2014 (10 977; 39% increase from baseline, range across English regions 11–89%); the trend was similar after adjustment for risk factors, with a rate ratio of 1·53 (95% CI 1·29–1·81) for 2014 versus 2005. Admissions for hypoglycaemia per 100 000 total hospital admissions increased from 63·6 to 78·9 between 2005–06 and 2010–11 (24% increase), and then fell to 72·3 per 100 000 in 2013–14 (14% overall increase). Accounting for diabetes prevalence data, rates declined from 4·64 to 3·86 admissions per 1000 person-years with diabetes between 2010–11 and 2013–14. We were unable to compare prevalence rates with data prior to 2010, as the populations were not comparable; data were available for all individuals prior to 2010 but only for those aged 17 years or older after 2010. With some differences across regions, from 2005 to 2014, the adjusted proportion of admissions to receive same-day discharge increased by 43·8% (from 18·9 to 27·1 same-day discharges per 100 admissions); in-hospital mortality decreased by 46·3% (from 4·2 to 2·3 deaths per 100 admissions); and 1 month readmissions decreased by 63·0% (from 48·1 to 17·8 per 100 readmissions).InterpretationOver 10 years, hospital admissions in England for hypoglycaemia increased by 39% in absolute terms and by 14% considering the general increase in hospitalisation; however, accounting for diabetes prevalence, there was a reduction of admission rates. Hospital length of stay, mortality, and 1 month readmissions decreased progressively and consistently during the study period. Given the continuous rise of diabetes prevalence, ageing population, and costs associated with hypoglycaemia, individual and national initiatives should be implemented to reduce the burden of hospital admissions for hypoglycaemia

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Abstract Aims/hypothesis Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. Methods We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score ('base' model). In the second model, we added to the 'base' model the 20 most common medical conditions and applied a stepwise backward selection of variables ('disease' model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. Conclusions/interpretation This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia

Rapid and High-Throughput Detection of Highly Pathogenic Bacteria by Ibis PLEX-ID Technology

In this manuscript, we describe the identification of highly pathogenic bacteria using an assay coupling biothreat group-specific PCR with electrospray ionization mass spectrometry (PCR/ESI-MS) run on an Ibis PLEX-ID high-throughput platform. The biothreat cluster assay identifies most of the potential bioterrorism-relevant microorganisms including Bacillus anthracis, Francisella tularensis, Yersinia pestis, Burkholderia mallei and pseudomallei, Brucella species, and Coxiella burnetii. DNA from 45 different reference materials with different formulations and different concentrations were chosen and sent to a service screening laboratory that uses the PCR/ESI-MS platform to provide a microbial identification service. The standard reference materials were produced out of a repository built up in the framework of the EU funded project “Establishment of Quality Assurances for Detection of Highly Pathogenic Bacteria of Potential Bioterrorism Risk” (EQADeBa). All samples were correctly identified at least to the genus level

In situ multi-frequency measurements of magnetic susceptibility as an indicator of planetary regolith maturity

Space weathering is now generally accepted to modify the optical and magnetic properties of airless planetary regoliths such as those on the Moon and Mercury. Under micrometeorite and ion bombardment, ferrous iron in such surfaces is reduced to metallic iron spheres, found in amorphous coatings on almost all exposed regolith grains. The size and number distribution of these particles and their location in the regolith all determine the nature and extent of the optical and magnetic changes. These parameters in turn reflect the formation mechanisms, temperatures, and durations involved in the evolution of the regolith. Studying them in situ is of intrinsic value to understanding the weathering process, and useful for determining the maturity of the regolith and providing supporting data for interpreting remotely sensed mineralogy. Fine-grained metallic iron has a number of properties that make it amenable to magnetic techniques, of which magnetic susceptibility is the simplest and most robust. The magnetic properties of the lunar regolith and laboratory regolith analogues are therefore reviewed and the theoretical basis for the frequency dependence of magnetic susceptibility presented. Proposed here is then an instrument concept using multi-frequency measurements of magnetic susceptibility to confirm the presence of fine grained magnetic material and attempt to infer its quantity and size distribution. Such an instrument would be invaluable on a future mission to an asteroid, the Moon, Mercury or other airless rocky Solar System body

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Aims/hypothesis: Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. Methods: We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score (‘base’ model). In the second model, we added to the ‘base’ model the 20 most common medical conditions and applied a stepwise backward selection of variables (‘disease’ model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. Results: In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. Conclusions/interpretation: This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia

Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity