Background: Germline knockout mice are invaluable in understanding the function of the targeted genes. Sometimes, however, unexpected phenotypes are encountered, due in part to the activation of compensatory mechanisms. Germline ablation of cardiac myosin light chain kinase (cMLCK) causes mild cardiac dysfunction with cardiomyocyte hypertrophy, whereas ablation in adult hearts results in acute heart failure with cardiomyocyte atrophy. We hypothesized that compensation after ablation of cMLCK is dependent on developmental staging and perinatal-onset of cMLCK ablation will result in more evident heart failure than germline ablation, but less profound when compared to adult-onset ablation.Methods and Results: The floxed-Mylk3 gene was ablated at the beginning of the perinatal stage using a single intra-peritoneal tamoxifen injection of 50 mg/kg into pregnant mice on the 19th day of gestation, this being the final day of gestation. The level of cMLCK protein level could no longer be detected 3 days after the injection, with these mice hereafter denoted as the perinatal Mylk3-KO. At postnatal day 19, shortly before weaning age, these mice showed reduced cardiac contractility with a fractional shortening 22.8 ± 1.0% (n = 7) as opposed to 31.4 ± 1.0% (n = 11) in controls. The ratio of the heart weight relative to body weight was significantly increased at 6.68 ± 0.28 mg/g (n = 12) relative to the two control groups, 5.90 ± 0.16 (flox/flox, n = 11) and 5.81 ± 0.33 (wild/wild/Cre, n = 5), accompanied by reduced body weight. Furthermore, their cardiomyocytes were elongated without thickening, with a long-axis of 101.8 ± 2.4 μm (n = 320) as opposed to 87.1 ± 1.6 μm (n = 360) in the controls.Conclusion: Perinatal ablation of cMLCK produces an increase of heart weight/body weight ratio, a reduction of contractility, and an increase in the expression of fetal genes. The perinatal Mylk3-KO cardiomyocytes were elongated in the absence of thickening, differing from the compensatory hypertrophy shown in the germline knockout, and the cardomyocyte thinning shown in adult-inducible knockout.
ObjectivesDerive and validate a shortlist of chief complaints to describe unscheduled acute and emergency care in Uganda.SettingA single, private, not-for profit hospital in rural, southwestern Uganda.ParticipantsFrom 2009 to 2015, 26 996 patient visits produced 42 566 total chief complaints for the derivation dataset, and from 2015 to 2017, 10 068 visits produced 20 165 total chief complaints for the validation dataset.MethodsA retrospective review of an emergency centre quality assurance database was performed. Data were abstracted, cleaned and refined using language processing in Stata to produce a longlist of chief complaints, which was collapsed via a consensus process to produce a shortlist and turned into a web-based tool. This tool was used by two local Ugandan emergency care practitioners to categorise complaints from a second longlist produced from a separate validation dataset from the same study site. Their agreement on grouping was analysed using Cohen’s kappa to determine inter-rater reliability. The chief complaints describing 80% of patient visits from automated and consensus shortlists were combined to form a candidate chief complaint shortlist.ResultsAutomated data cleaning and refining recognised 95.8% of all complaints and produced a longlist of 555 chief complaints. The consensus process yielded a shortlist of 83 grouped chief complaints. The second validation dataset was reduced in Stata to a longlist of 451 complaints. Using the shortlist tool to categorise complaints produced 71.5% agreement, yielding a kappa of 0.70 showing substantial inter-rater reliability. Only one complaint did not fit into the shortlist and required a free-text amendment. The two shortlists were identical for the most common 14 complaints and combined to form a candidate list of 24 complaints that could characterise over 80% of all emergency centre chief complaints.ConclusionsShortlists of chief complaints can be generated to improve standardisation of data entry, facilitate research efforts and be employed for paper chart usage.
Acute urinary retention is a common problem in the emergency department. Patients can present in significant distress, necessitating the placement of a urinary catheter. Foley catheter placement can be difficult to accomplish depending on the etiology of the retention and the degree of the obstruction. In the case presented here, we used ultrasound guidance, a guidewire, and a Foley catheter to successfully relieve a patient’s urinary retention after multiple failed attempts.
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