Non-redundancy of cytidine deaminases in class switch recombination

Class switch recombination (CSR), somatic hypermutation, and gene conversion are immunoglobulin diversification mechanisms that are strictly dependent on the activity of the activation-induced cytidine deaminase (AID). The precise role and substrate(s) of AID in these processes remain to be well defined. The closest homologue of AID is APOBEC-1, a bona fide mRNA-editing enzyme, which shares with AID the ability to deaminate cytidines within single-stranded DNA in vitro and in prokaryotic cells. To determine whether APOBEC-1 can therefore substitute for AID in activated B cells, we expressed human AID, a catalytic mutant thereof, and rat APOBEC-1 in AID-deficient murine B cells. Whereas AID rescued CSR, neither the inactive mutant nor APOBEC-1 could complement AID deficiency. This indicates that cytidine deaminase activity is necessary but not sufficient to initiate CSR, and suggests that AID is specifically targeted to its cognate substrate, the immunoglobulin genes or a distinct mRNA, by an as-yet-unknown mechanism.     

Nursing constraint models for electronic health records: a vision for domain knowledge governance

Various forms of electronic health records (EHRs) are currently being introduced in several countries. Nurses are primary stakeholders and need to ensure that their information and knowledge needs are being met by such systems information sharing between health care providers to enable them to improve the quality and efficiency of health care service delivery for all subjects of care. The latest international EHR standards have adopted the openEHR approach of two-level modelling. The first level is a stable information model determining structure, while the second level consists of constraint models or 'archetypes' that reflect the specifications or clinician rules for how clinical information needs to be represented to enable unambiguous data sharing. The current state of play in terms of international health informatics standards development activities is providing the nursing profession with a unique opportunity and challenge. Much work has been undertaken internationally in the area of nursing terminologies and evidence-based practice. This paper argues that to make the most of these emerging technologies and EHRs we must now concentrate on developing a process to identify, document, implement, manage and govern our nursing domain knowledge as well as contribute to the development of relevant international standards. It is argued that one comprehensive nursing terminology, such as the ICNP or SNOMED CT is simply too complex and too difficult to maintain. As the openEHR archetype approach does not rely heavily on big standardised terminologies, it offers more flexibility during standardisation of clinical concepts and it ensures open, future-proof electronic health records. We conclude that it is highly desirable for the nursing profession to adopt this openEHR approach as a means of documenting and governing the nursing profession's domain knowledge. It is essential for the nursing profession to develop its domain knowledge constraint models (archetypes) collaboratively in an international context.     

Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.     

Skill needs for nurses in their role as health informatics professionals: a survey in the context of global health informatics education

In the process of developing global health informatics education, a common understanding of educational outcomes is required. Therefore, an educational framework for health informatics professionals is desirable to support student mobility, trans-national and borderless education. Nurses form a significant part of the health workforce and need to be properly educated for their roles in health informatics. To ascertain their perceptions of needs and priorities, we developed a web-based questionnaire and surveyed Australian nurses on the preferred knowledge/skills set for health informatics professionals. Among others, the questionnaire is based on the International Medical Informatics Association's (IMIA) set of recommendations on education and IMIA's scientific map. Benner's five levels of competencies were applied to measure the degree of competency required for each skill/knowledge. Altogether, 82 Australian nurses completed the questionnaire. The nurses' perceived degree of competency required for a total of 74 specific skills and knowledge in five skill categories is presented in this paper as well as the overall results for each of the five categories. Further, significant differences between the nurses' primary roles and primary interest in health informatics are discussed. The development of a comprehensive health informatics education framework needs to take into account nurses as well as other health professionals. Repeating the survey in other countries and for various professions is essential to develop an international educational framework.     

Impaired Ca-signaling in astrocytes from the Ts16 mouse model of Down syndrome

The trisomy 16 mouse model of Down syndrome has been used to compare calcium (Ca)-homeostasis and Ca-signaling in astrocytes from trisomic mice and from diploid littermates. Ratio calcium-imaging of Fura-2/AM loaded primary astroglial cultures prepared from the hippocampus shows that resting Ca levels are on average significantly higher in trisomic than in the control astrocytes (280 vs. 120 nM). Serotonin (3 μM) and glutamate (30–300 μM) evoked transient Ca-increases from 400 to 600 nM in euploid but from only 20 to 150 nM in trisomic astrocytes. Imaging of ATP-driven Ca-accumulation in cellular organelles revealed a significantly stronger uptake of Ca in trisomic astrocytes that might buffer cytosolic Ca-increases. Our results demonstrate major disturbances in Ca-signaling in trisomic astrocytes that are likely to be of pathophysiological relevance.     

Factors influencing active avoidance behavior in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic lesioned rats maintained at preoperative body weight received an equal number of shocks while emitting significantly fewer responses than controls in a lever-pressing free-operant avoidance paradigm, and performed as well as unoperated animals in lever-pressing and shuttle box (both 1- and 2-way) discriminated avoidance tasks. The failure of VMH lesions to facilitate performance in the 2-way avoidance paradigm was probably the result of a ceiling effect. With the exception of the simple one-way avoidance task, obese lesioned rats were markedly impaired in the acquisition of all active avoidance behavior, but escape behavior was not affected. When tested in a free-operant paradigm, the avoidance performance of well trained lesioned animals varied inversely with body weight. As obese rats displayed lower flinch thresholds to shock than controls and similar levels of activity and responding as lean lesioned animals, it was concluded that their impaired avoidance behavior was not due to changes in sensitivity or mobility. The possible relation to other VMH lesion- and/or obesity-induced deficits is discussed.     

The learning experiences of dyslexic medical students during the COVID-19 pandemic: a phenomenological study

Advances in Health Sciences Education - Dyslexia is a Specific Learning Difficulty that impacts on reading and writing abilities. During the COVID-19 pandemic, medical schools have been forced to...