There has been a rapid increase in the number of prescriptions for baclofen (BLF), gabapentin (GBP) and pregabalin (PGL) in the UK since their introduction to therapy. Recent studies across the ...European Union and USA have shown the illicit abuse potential of these drugs and deaths have been observed. A simple, reliable and fully validated method was developed for the screening and quantification of BLF, GBP and PGL in human post-mortem (PM) blood. The analytes and their deuterated analogs as internal standard were extracted from blood using a single addition acetonitrile protein precipitation reaction followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous confirmation and quantification. The assay was linear from 0.05 to 1.00 µg/mL for BLF and 0.5 to 50.0 µg/mL for GBP and PGL, respectively with r2 > 0.999 (n = 9) for all analytes. Intra-day and inter-day imprecisions (n = 80) were calculated using one-way ANOVA; no significant difference (P > 0.99) was observed for all analytes over 8 non-consecutive days. The average recovery for all analytes was >98.9%. The limits of detection and quantification were both 0.05 µg/mL for BLF, and 0.5 µg/mL for GBP and PGL. The method was highly selective with no interference from endogenous compounds or from 54 drugs commonly encountered in PM toxicology. To prove method applicability, 17 PM blood samples submitted for analysis were successfully analyzed. The concentration range observed in PM blood for BLF was 0.08-102.00 µg/mL (median = 0.25 µg/mL), for GBP 1.0-134.0 µg/mL (median = 49.0 µg/mL) and 2.0-540.0 µg/mL (median = 42.0 µg/mL) for PGL.
Hypertension is associated with enhanced cardiac sympathetic transmission, although the exact mechanisms underlying this are still unknown. We hypothesized that defective function of the ...norepinephrine uptake transporter (NET) may contribute to the sympathetic phenotype of the spontaneously hypertensive rat, and that this may occur before the development of hypertension itself. The dynamic kinetics of NET were monitored temporally using a novel fluorescent assay of the transporter in cultured postganglionic sympathetic neurons from the cardiac stellate ganglion, the superior cervical ganglion, the celiac ganglia/superior mesenteric ganglia, and the renal sympathetic chain. All NET activity was blocked by desipramine. NET rate was significantly impaired in cardiac stellate sympathetic neurons from the prehypertensive spontaneously hypertensive rat compared with age-matched normotensive Wistar-Kyoto rats. A similar response was seen in hypertensive spontaneously hypertensive rats stellate sympathetic neurons. However, no reduction in transporter rate was observed at either age in the other major noncardiac sympathetic ganglia. Depolarization of cardiac stellate neurons by electrical field stimulation further potentiated the difference in transporter rate observed between the hypertensive and normotensive rats at both developmental ages. In conclusion, dysregulation of the norepinephrine transporter in the hypertensive rat is ganglion-specific, where NET impairment in the stellate neurons may contribute to the increased cardiac norepinephrine spillover seen in hypertension.
The incidence of esophageal carcinoma continues to increase whilst its prognosis remains poor. The most dramatic reduction in mortality is likely to follow early diagnosis of the preinvasive ...precursor lesion, Barrett's esophagus (BE), coupled with treatment of dysplastic lesions. The major risk factor for BE is gastroesophageal reflux disease, however this is highly prevalent and only a small proportion of individuals have BE, therefore an endoscopy-based screening strategy to detect BE is unfeasible. Minimally invasive esophageal sampling devices offer an alternative, cost-effective strategy which can be deployed within an at-risk population in a primary care setting to identify individuals with probable BE who can then be referred for endoscopic confirmation. The device that has currently progressed furthest in clinical trials is the Cytosponge
which collects cells from the gastric cardia, gastroesophageal junction and along the whole esophageal length. The cell sample is processed into a formalin-fixed paraffin-embedded block and sections assessed for the presence of intestinal metaplasia. TFF3 immunohistochemistry has consistently been shown to be a valuable adjunct that increases the accuracy of the Cytosponge
test by highlighting early goblet cells which may be missed on morphological assessment and by allowing pseudogoblet cells to be differentiated from true goblet cells.
The incidence of esophageal carcinoma continues to increase whilst its prognosis remains poor. The most dramatic reduction in mortality is likely to follow early diagnosis of the preinvasive ...precursor lesion, Barrett's esophagus (BE), coupled with treatment of dysplastic lesions. The major risk factor for BE is gastroesophageal reflux disease, however this is highly prevalent and only a small proportion of individuals have BE, therefore an endoscopy‐based screening strategy to detect BE is unfeasible. Minimally invasive esophageal sampling devices offer an alternative, cost‐effective strategy which can be deployed within an at‐risk population in a primary care setting to identify individuals with probable BE who can then be referred for endoscopic confirmation. The device that has currently progressed furthest in clinical trials is the CytospongeTM which collects cells from the gastric cardia, gastroesophageal junction and along the whole esophageal length. The cell sample is processed into a formalin‐fixed paraffin‐embedded block and sections assessed for the presence of intestinal metaplasia. TFF3 immunohistochemistry has consistently been shown to be a valuable adjunct that increases the accuracy of the CytospongeTM test by highlighting early goblet cells which may be missed on morphological assessment and by allowing pseudogoblet cells to be differentiated from true goblet cells.
This study extends our knowledge on co-creation of value in higher education. The paper examines the relationship between support, co-creation of value and students' satisfaction, as well as ...moderating factors including mode of study and fee status, via 979 survey responses from undergraduate students. Analysis using partial least squares found support to be important in determining co-creation of value and, in turn, student satisfaction. Results indicated that student satisfaction is positively influenced through students accessing support mechanisms and their active involvement in co-creation of value activities. Our findings further reveal that fee-paying students are more satisfied when they participate in co-creation activities and access support mechanisms. No significant differences between transnational and domestic students are found.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To understand healthcare worker and patient experience with peripheral intravenous catheter (PIVC) insertion in patients with difficult intravenous access (DIVA) including the use of ultrasound (US). ...Descriptive study using 1-on-1 semi-structured interviews conducted between August 2020 and January 2021. Purposeful sampling was used to recruit healthcare practitioners (HCPs) and patients with DIVA who had PIVC experience. Data were analysed using inductive thematic analysis. Interview data were than mapped to the implementation theory Behaviour Change Wheel to inform implementation strategies. In total 78 interviews (13 patients; 65 HCPs) were completed with respondents from metropolitan (60%), regional (25%) and rural/remote (15%) settings across Australia. Thematic analysis revealed 4 major themes: i) Harmful patient experiences persist, with patient insights not leveraged to effect change; ii) 'Escalation' is just a word on the front lines; iii) Heightened risk of insertion failure without resources and training; and iv) Paving the way forward-'measures need to be in place to prevent failed insertion attempts. Themes were mapped to the behaviour change wheel and implementation strategies developed, these included: staff education, e-health record for DIVA identification, DIVA standard of care and DIVA guidelines to support escalation and ultrasound use. DIVA patients continue to have poor healthcare experiences with PIVC insertion. There is poor standardisation of DIVA assessment, escalation, US use and clinician education across hospitals. Quality, safety, and education improvement opportunities exist to improve the patient with DIVA experience and prevent traumatic insertions. We identified a number of implementation strategies to support future ultrasound and DIVA pathway implementation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This systematic review aimed to identify oncology nurses’ experiences of using health information systems (HIS) in the delivery of cancer care.
The electronic databases searched included CINAHL, ...MEDLINE (EBSCO host), SCOPUS, Web of Science Core Collection, Google Scholar, OVID, and ProQuest Central (using advanced search strategy) and hand searching of reference lists of the included articles and relevant systematic reviews. Studies published in English language were examined.
Twenty-six studies were included. Three themes emerged: (1) the transparency and application of the nursing process within HIS, (2) HIS enhancing and facilitating communication between nurses and patients, and (3) the impact of HIS on the elements of person-centered care. Nurses’ experiences with HIS were overall positive. However, digital systems do not fully capture all elements of the nursing processes; this was confirmed in this review, through the nurses’ lens. Most studies used HIS for symptom reporting and monitoring within non-inpatient settings and largely biomedical and lack insight into the person-centeredness and overall holistic care.
There are evidently varied views of HIS adoption across the globe. HIS can improve health-related quality of life and symptom burden, including self-reporting of symptoms among patients. However, there is a need for ongoing high-quality research, and clearer reporting than is evident in the current 26 studies, to fully understand the impact of HIS within the nursing processes and patient outcomes across all specialty cancer fields.
Understanding microplastic exposure and effects is critical to understanding risk. Here, we used large, in-lake closed-bottom mesocosms to investigate exposure and effects on pelagic freshwater ...ecosystems. This article provides details about the experimental design and results on the transport of microplastics and exposure to pelagic organisms. Our experiment included three polymers of microplastics (PE, PS, and PET) ranging in density and size. Nominal concentrations ranged from 0 to 29,240 microplastics per liter on a log scale. Mesocosms enclosed natural microbial, phytoplankton, and zooplankton communities and yellow perch (Perca flavescens). We quantified and characterized microplastics in the water column and in components of the food web (biofilm on the walls, zooplankton, and fish). The microplastics in the water stratified vertically according to size and density. After 10 weeks, about 1% of the microplastics added were in the water column, 0.4% attached to biofilm on the walls, 0.01% within zooplankton, and 0.0001% in fish. Visual observations suggest the remaining >98% were in a surface slick and on the bottom. Our study suggests organisms that feed at the surface and in the benthos are likely most at risk, and demonstrates the value of measuring exposure and transport to inform experimental designs and achieve target concentrations in different matrices within toxicity tests.
Normal readers make immediate and precise adjustments in eye movements during sentence reading in response to individual word features, such as lexical difficulty (e.g., common or uncommon words) or ...word length. Our purpose was to assess the effect of infantile nystagmus (IN) on these adaptive mechanisms.
Eye movements were recorded from 29 participants with IN (14 albinism, 12 idiopathic, and 3 congenital stationary night blindness) and 15 controls when reading sentences containing either common/uncommon words or long/short target words. Parameters assessed included: duration of first foveation/fixation, number of first-pass and percentage second-pass foveations/fixations, percentage words skipped, gaze duration, acquisition time (gaze + nongaze duration), landing site locations, clinical and experimental reading speeds.
Participants with IN could not modify first foveation durations in contrast to controls who made longer first fixations on uncommon words (P < 0.001). Participants with IN made more first-pass foveations on uncommon and long words (P < 0.001) to increase gaze durations. However, this also increased nongaze durations (P < 0.001) delaying acquisition times. Participants with IN reread shorter words more often (P < 0.005). Similar to controls, participants with IN landed more first foveations between the start and center of long words. Reading speeds during experiments were lower in IN participants compared to controls (P < 0.01).
People with IN make more first-pass foveations on uncommon and long words influencing reading speeds. This demonstrates that the "slow to see" phenomenon occurs during word reading in IN. These deficits are not captured by clinical reading charts.
The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumour is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array ...could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago-gastric adenocarcinomas.
Gene expression profiling from oesophago-gastric tumours (n=75) and preinvasive stages (n=57) identified the active signalling pathways, which was confirmed using immunohistochemistry (n=434). RTK arrays on a cell line panel (n=14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumour samples (n=46).
MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p<0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumours demonstrated diverse activation profiles and 65% of cases had two or more active RTKs.
The MAPK pathway is commonly activated in oesophago-gastric cancer following activation of a variety of RTKs. Molecular phenotyping can inform a rational choice of targeted therapy.
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