The effect of experience, simulator-training and biometric feedback on manual ventilation technique

Objective To determine the frequency of provision and main providers (veterinary surgeons, nurses or trainees) of manual ventilation in UK veterinary practices. Furthermore, to determine the variation in peak inspiratory (inflation) pressure (PIP), applied to a lung model during manual ventilation, by three different groups of operators (inexperienced, experienced and specialist), before and after training. Study Design Questionnaire survey. Development of a lung model simulator with real-time biometric (manometry) feedback capability and its testing as a training tool on operators with a range of experiences. Methods Postal questionnaires were sent to 100 randomly selected veterinary practices. The lung model simulator was manually ventilated, in a staged process over three weeks, with and without real-time biometric feedback (PIP display), by three groups of volunteer operators: inexperienced, experienced and specialist. Results The questionnaires determined that veterinary nurses were responsible for providing the majority of manual ventilation in veterinary practices, mainly drawing on theoretical knowledge rather than any specific training. Thoracic surgery and apnoea were the main reasons for provision of manual ventilation. Specialists performed well when manually ventilating the lung model, regardless of feedback-training. Both inexperienced and experienced operators showed significant improvement in technique when using the feedback training tool: variation in PIP decreased significantly until subjects provided manual ventilation at peak inspiratory pressures within the defined optimum range. Preferences for different forms of feedback (graphical, numerical or scale display), revealed that the operators’ choice was not always the method which gave least variation in PIP. Conclusions and Clinical Relevance This study highlighted a need for training in manual ventilation at an early stage in veterinary and veterinary nursing careers and demonstrated how feedback is important in the process of experiential learning. A manometer device which can provide immediate feedback during training, or indeed in a real clinical setting, should improve patient safety

Enhanced Vaccine Effectiveness during the Delta Phase of the COVID-19 Pandemic in the Medicare Population Supports a Multilayered Prevention Approach

Throughout the pandemic, individuals 65 years and older have contributed most COVID-19 related deaths. To best formulate effective vaccination and other prevention policies to protect older adults, large scale observational studies of these higher risk individuals are needed. We conducted a Vaccine Effectiveness (VE) study during the B.1.617.2 Delta variant phase of the pandemic in July and August 2021 in a cohort of 17 million Medicare beneficiaries of which 5.7 million were fully vaccinated. We found that individuals fully vaccinated with the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines in January 2021 had 2.5 times higher breakthrough infections and hospitalizations than those fully vaccinated in March 2021, consistent with waning of vaccine-induced immunity. Measuring VE weekly, we found that VE against hospitalization, and even more so against infection, increased from July 2021 through August 2021, suggesting that in addition to the protective role of vaccination, increased masking or social distancing might have contributed to the unexpected increase in VE. Ongoing monitoring of Medicare beneficiaries should be a priority as new variants continue to emerge, and the VE of the new bivalent vaccines remains to be established. This could be accomplished with a large Medicare claims database and the analytics platform used for this study

Expression of rat fibroblast growth factor receptor 1 as three splicing variants during kidney development

Fibroblast growth factors (FGF) are known to participate in the processes of embryogenesis and angiogenesis. This study was undertaken to examine the transcriptional and posttranscriptional regulation of the FGF receptor 1 (FGFR-1) subclass in the embryonic rat kidney. Two full-length FGF receptor cDNAs were cloned using low-stringency screening of a neonatal rat kidney library with a chicken FGFR-1 cDNA probe. Sequencing revealed these cloned cDNAs to be rat homologues of the FGFR-1 subtype, with the two clones representing splicing variants ?? and ?? of the FGFR-1. Evidence for renal expression of a third splicing variant (??) was obtained by use of the polymerase chain reaction. Splicing variants ?? and ?? of FGFR-1 are predicted to produce cell-surface FGF receptors with three and two immunoglobulin-like domains, respectively, whereas the ??-isoform may represent an intracellular form of the receptor. Although all three splicing variants were expressed in the developing kidney at days 14, 17, and 20 of gestation, at neonatal days 1 and 7 and in mature rats the ??-isoform was present in vastly larger abundance than ??- and ??-isoforms at all stages studied. Northern blot analysis revealed enhanced expression of FGFR-1 in the neonatal compared with the mature kidney. It is concluded that FGFR-1 is expressed in the kidney predominantly as the ??-isoform splicing variant and that expression of this receptor is enhanced during kidney development.open171

Apical Plasma Membrane Mispolarization of NaK-ATPase in Polycystic Kidney Disease Epithelia Is Associated with Aberrant Expression of the β2 Isoform

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease of the kidney, characterized by cystic enlargement of renal tubules, aberrant epithelial proliferation, and ion and fluid secretion into the lumen. Previous studies have shown abnormalities in polarization of membrane proteins, including mislocalization of the NaK-ATPase to the apical plasma membranes of cystic epithelia. Apically located NaK-ATPase has previously been shown to be fully functional in vivo and in membrane-grown ADPKD epithelial cells in vitro, where basal-to-apical 22Na transport was inhibited by application of ouabain to the apical membrane compartment. Studies were conducted with polymerase chain reaction-generated specific riboprobes and polyclonal peptide antibodies against human sequences of α1, α3, β1, and β2 subunits of NaK-ATPase. High levels of expression of α1 and β1 messenger RNA were detected in ADPKD and age-matched normal adult kidneys in vivo, whereas β2 messenger RNA was detected only in ADPKD kidneys. Western blot analysis and immunocytochemical studies showed that, in normal adult kidneys, peptide subunit-specific antibodies against α1 and β1 localized to the basolateral membranes of normal renal tubules, predominantly thick ascending limbs of Henle’s loop. In ADPKD kidneys, α1 and β2 subunits were localized to the apical epithelial cell membranes, whereas β1 was distributed throughout the cytoplasm and predominantly in the endoplasmic reticulum, but was not seen associated with cystic epithelial cell membranes or in cell membrane fractions. Polarizing, renal-derived epithelial Madin Darby canine kidney cells, stably expressing normal or N-terminally truncated chicken β1 subunits, showed selective accumulation in the basolateral Madin Darby canine kidney cell surface, whereas c-myc epitope-tagged chicken β2 or human β2 subunits accumulated selectively in the apical cell surface. Similarly, human ADPKD epithelial cell lines, which endogenously expressed α1 and β2 NaK-ATPase subunits, showed colocalization at the apical cell surface and coassociation by immunoprecipitation analysis. These results are consistent with a model in which the additional transcription and translation of the β2 subunit of NaK-ATPase may result in the apical mislocalization of NaK-ATPase in ADPKD cystic epithelia