The IntaRNA algorithm enables fast and accurate prediction of RNA-RNA hybrids by incorporating seed constraints and interaction site accessibility. Here, we introduce IntaRNAv2, which enables enhanced parameterization as well as fully customizable control over the prediction modes and output formats. Based on up to date benchmark data, the enhanced predictive quality is shown and further improvements due to more restrictive seed constraints are highlighted. The extended web interface provides visualizations of the new minimal energy profiles for RNA-RNA interactions. These allow a detailed investigation of interaction alternatives and can reveal potential interaction site multiplicity. IntaRNAv2 is freely available (source and binary), and distributed via the conda package manager. Furthermore, it has been included into the Galaxy workflow framework and its already established web interface enables ad hoc usage.
Background and Purpose- The impact of a mobile stroke unit (MSU) on access to intraarterial thrombectomy (IAT) is a prespecified BEST-MSU substudy (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). On the MSU, IAT decision-making steps, such as computed tomography, neurological exam, and tPA (tissue-type plasminogen activator) treatment are completed before emergency department arrival. We hypothesized that such pre-ED assessment of potential IAT patients on an MSU improves the time from ED arrival to skin puncture time (door-to-puncture-time, DTPT). Methods- BEST-MSU is a prospective comparative effectiveness study of MSU versus standard management by emergency medical services (EMS). We compared ED DTPT among the following groups of MSU and EMS patients: all IAT patients, IAT patients post-tPA, and IAT patients post-tPA meeting thrombolytic adjudication criteria over the first 4 years of the study. Results- From August 2014 to July 2018, a total of 161 patients underwent IAT. Ninety-four patients presented to the ED via the MSU and 67 by EMS. One hundred forty patients received tPA before IAT, 85 in the MSU arm, and 55 in the EMS arm. One hundred twenty-six patients received tPA within thrombolytic adjudication criteria: 76 MSU and 50 EMS. DTPT in minutes was shorter for MSU patients (all IAT MSU versus EMS 89 versus 99, P=0.01; IAT post-tPA MSU versus EMS 93 versus 100, P=0.03; and IAT post-tPA within adjudicated criteria MSU versus EMS 93 versus 99.5, P=0.03). From 2014 to 2018, DTPT decreased at a faster rate for EMS compared with MSU-managed patients, improving by about an hour. Conclusions- Pre-ED IAT evaluation on an MSU results in faster DTPT compared with arrival by EMS. Since 2014, dramatic improvement in ED IAT metrics has attenuated this difference. However, DTPT in all groups indicates substantial room for improvement.
Introduction: The impact of a Mobile stroke unit (MSU) on access to Endovascular Thrombectomy (ET) is a pre-specified BEST-MSU sub-study. On the MSU, ET decision-making steps such as CT, neurologic exam, and tPA treatment are completed prior to Emergency Room (ER) arrival. We hypothesized that such pre-ER assessment of potential ET patients on a MSU improves metrics. Methods: BEST-MSU is a prospective comparative effectiveness study of MSU vs Standard Management by Emergency Medical Services (SM). We compared ER door-to-puncture-time (mins, DTPT) among the following groups of MSU and SM patients: all ET patients (ETP), ET patients post-tPA (ETT), and ET patients post-tPA meeting thrombolytic adjudication criteria (ETTA) over the first four years of the study. Results: There were 161 ETP (67 SM, 94 MSU), 140 ETT (55 SM, 85 MSU), and 126 ETTA (50 SM, 76 MSU) patients. DTPT was shorter for MSU patients (ETP 89 vs 99, p=0.01; ETT 93 vs 100, p=0.03; ETTA 93 vs 99.5, p=0.03). From 2015 to 2018, DTPT decreased at a faster rate for SM compared with MSU-managed patients, improving by about an hour (Figure). Conclusion: Pre-ER ET evaluation on a MSU results in faster DTPT. Since 2015, dramatic improvement in ER ET metrics has attenuated this difference. However, DTPT of 90-100 mins in all groups indicates substantial room for improvement.
The small RNA AbcR1 regulates the expression of ABC transporters in the plant pathogen Agrobacterium tumefaciens, the plant symbiont Sinorhizobium meliloti, and the human pathogen Brucella abortus. A combination of proteomic and bioinformatic approaches suggested dozens of AbcR1 targets in A. tumefaciens. Several of these newly discovered targets are involved in the uptake of amino acids, their derivatives, and sugars. Among the latter is the periplasmic sugar-binding protein ChvE, a component of the virulence signal transduction system. We examined 16 targets and their interaction with AbcR1 in close detail. In addition to the previously described mRNA interaction site of AbcR1 (M1), the CopraRNA program predicted a second functional module (M2) as target-binding site. Both M1 and M2 contain single-stranded anti-SD motifs. Using mutated AbcR1 variants, we systematically tested by band shift experiments, which sRNA region is responsible for mRNA binding and gene regulation. On the target site, we find that AbcR1 interacts with some mRNAs in the translation initiation region and with others far into their coding sequence. Our data show that AbcR1 is a versatile master regulator of nutrient uptake systems in A. tumefaciens and related bacteria.
Rapid treatment of acute ischemic stroke (AIS) depends on sufficient staffing which differs between Stroke Centers and Stroke Units in Switzerland. We studied the effect of admission time on performance measures of AIS treatment and related temporal trends over time.We compared treatment rates, door-to-image-time, door-to-needle-time, and door-to-groin-puncture-time in stroke patients admitted during office hours (Monday-Friday 8:00-17:59) and non-office hours at all certified Stroke Centers and Stroke Units in Switzerland, as well as secular trends thereof between 2014 and 2019, using data from the Swiss Stroke Registry. Secondary outcomes were modified Rankin Scale and mortality at 3 months.Data were eligible for analysis in 31,788 (90.2%) of 35,261 patients. Treatment rates for IVT/EVT were higher during non-office hours compared with office hours in Stroke Centers (40.8 vs 36.5%) and Stroke Units (21.8 vs 18.5%). Door-to-image-time and door-to-needle-time increased significantly during non-office hours. Median (IQR) door-to-groin-puncture-time at Stroke Centers was longer during non-office hours compared to office hours (84 (59-116) vs 95 (66-130) minutes). Admission during non-office hours was independently associated with worse functional outcome (1.11 [95%CI: 1.04-1.18]) and increased mortality (1.13 [95%CI: 1.01-1.27]). From 2014 to 2019, median door-to-groin-puncture-time improved and the treatment rate for wake-up strokes increased.Despite differences in staffing, patient admission during non-office hours delayed IVT to a similar, modest degree at Stroke Centers and Stroke Units. A larger delay of EVT was observed during non-office hours, but Stroke Centers sped up delivery of EVT over time. Patients admitted during non-office hours had worse functional outcomes, which was not explained by treatment delays.
Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes.Admission hyponatremia is associated with worse clinical outcome in stroke patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination.This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values.We analyzed data of hospitalized patients treated at University Hospital of Basel.Stroke patients whose data and informed consent were available.Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records.Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio [OR] 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization.In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.
Marine algae are known to contain a wide variety of bioactive compounds, many of which have commercial applications in pharmaceutical, medical, cosmetic, nutraceutical, food and agricultural industries. Natural antioxidants, found in many algae, are important bioactive compounds that play an important role against various diseases and ageing processes through protection of cells from oxidative damage. In this respect, relatively little is known about the bioactivity of Hawaiian algae that could be a potential natural source of such antioxidants. The total antioxidant activity of organic extracts of 37 algal samples, comprising of 30 species of Hawaiian algae from 27 different genera was determined. The activity was determined by employing the FRAP (Ferric Reducing Antioxidant Power) assays. Of the algae tested, the extract of Turbinaria ornata was found to be the most active. Bioassay-guided fractionation of this extract led to the isolation of a variety of different carotenoids as the active principles. The major bioactive antioxidant compound was identified as the carotenoid fucoxanthin. These results show, for the first time, that numerous Hawaiian algae exhibit significant antioxidant activity, a property that could lead to their application in one of many useful healthcare or related products as well as in chemoprevention of a variety of diseases including cancer.
In this study, we aimed to investigate whether body composition analysis (BCA) derived from bioelectrical impedance vector analysis (BIVA) could be used to monitor the hydration status of patients with acute heart failure (AHF) during intensified diuretic therapy.This observational, single-centre study involved a novel, validated eight-electrode segmental body composition analyser to perform BCA derived from BIVA with an alternating current of 100 μA at frequencies of 5, 7.5, 50, and 75 kHz. The BCA-derived and BIVA-derived parameters were estimated and compared with daily body weight measurements in hospitalized patients with AHF. A total of 867 BCA and BIVA assessments were conducted in 142 patients (56.3% men; age 76.8 ± 10.7 years). Daily changes in total body water (TBW) and extracellular water (ECW) were significantly associated with changes in body weight in 62.2% and 89.1% of all measurements, respectively (range, ±1 kg). Repeated measures correlation coefficients between weight loss and TBW loss resulted with rho 0.43, P < 0.01, confidence interval (CI) [0.36, 0.50] and rho 0.71, P > 0.01, CI [0.67, 0.75] for ECW loss. Between the first and last assessments, the mean weight loss was -2.5 kg, compared with the -2.6 L mean TBW loss and -1.7 L mean ECW loss. BIVA revealed an increase in mean Resistance R and mean Reactance Xc across all frequencies, with the subsequent reduction in body fluid (including corresponding body weight) between the first and last assessments.Body composition analysis derived from BIVA with a focus on ECW is a promising approach to detect changes in hydration status in patients undergoing intensified diuretic therapy. Defining personalized BIVA reference values using bioelectrical impedance devices is a promising approach to monitor hydration status.
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