Anti-V antigen antibody protects macrophages from Yersinia pestis -induced cell death and promotes phagocytosis

The pathogenic Yersinia spp. harbor a common plasmid (pYV) essential for virulence. The plasmid encodes a type III secretion system that functions to translocate Yersinia outer proteins (Yops) into the host cytosol. Within the host cell, the Yops act to inhibit phagocytosis and induce apoptosis. One of the plasmid-encoded proteins, virulence antigen (V), is a major protective immunogen that is involved in Yop translocation. Yersinia pestis, like the enteric Yersinia spp., was both resistant to phagocytosis by and cytotoxic for J774.A1, a murine macrophage cell line. Both of these activities were dependent on culture of the bacteria at 37 degrees C for 1.5-2 h before infection. However, extending the preculture period at 37 degrees C to 24 h, which induced formation of a capsule, completely blocked cytotoxicity. Treating the bacteria with either rabbit polyclonal anti-V antibodies (R anti-V) or monoclonal antibody (MAb) 7.3, antibodies specific for V and protective against plague in vivo, protected J774.A1 cells from Y. pestis -induced cell death and also reversed the inhibition of phagocytosis. Whereas protection against cell cytotoxicity was afforded by the F(ab')(2) portion of R anti-V, the ability of anti-V to induce uptake of Y. pestis appeared to be dependent on the Fc portion of the Ab. The protective epitope(s) recognized by R anti-V was contained in the central region of Y. pestis V (aa 135-275) and were partially cross reactive with Y. pseudotuberculosis and Y. enterocolitica serotype 08 V antigens.     

Cognitive function after anaesthesia in the elderly

Despite advances in peri operative care, a significant percentage of elderly patients experience transient post operative delirium and/or long-term post-operative cognitive dysfunction (POCD). This chapter reviews the aetiology, clinical features, preventive strategies and treatment of these syndromes. Pre-operative, intra-operative, and post-operative risk factors for delirium and POCD following cardiac and non-cardiac surgery are discussed. It is most likely that the aetiology of delirium and POCD is multifactorial and may include factors such as age, decreased pre-operative cognitive function, general health status and, possibly, intra-operative events. Currently there is no single therapy that can be recommended for treating post-operative cognitive deterioration. Primary prevention of delirium and POCD is probably the most effective treatment strategy. Several large clinical trials show the effectiveness of multicomponent intervention protocols that are designed to target well-documented risk factors in order to reduce the incidence of post-operative delirium and, possibly, POCD in the elderly.     

Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis

BACKGROUND: Modest maternal protein restriction leads to hypertension and a reduced number of glomeruli in adult male but not female offspring. This study determined whether a more severe protein restriction has equivalent effects on male and female rat offspring, and examined the role of nephrogenesis in this programming. METHODS: Sprague-Dawley rats were fed a protein-restricted (5% protein) diet throughout (LLP), or during the first (LLP/NP) or second (NP/LLP) half of pregnancy. Controls ate a normal diet (NP, 19% protein). Adult offspring were chronically instrumented at 22 weeks; glomerular number and volume were estimated using stereologic techniques. RESULTS: Mean arterial pressures in male offspring were significantly higher in LLP (136 +/- 2 mm Hg) or NP/LLP (137 +/- 2 mm Hg) than in LLP/NP (125 +/- 1 mm Hg) or NP (125 +/- 2 mm Hg). Moreover, the hypertension was salt-sensitive (increase of 16 +/- 4 mm Hg in LLP on a high Na(+) diet compared to 2 +/- 2 mm Hg in NP). Glomerular number (per kidney) was reduced (15,400 +/- 2,411 in LLP vs. 27,208 +/- 1,534 in NP) but average individual glomerular volume was not different (1.98 +/- 0.18 106 micro(3) in LLP vs. 2.01 +/- 0.14 106 micro(3) in NP). Female offspring showed qualitatively similar results. CONCLUSION: Severe maternal dietary protein restriction reduces glomerular number and programs for salt-sensitive adult hypertension in both female and male offspring. The window of sensitivity of adult blood pressure to prenatal protein restriction falls within the period of nephrogenesis in the rat. These data are consistent with the hypothesis that maternal protein restriction causes adult hypertension in the offspring through impairment of renal development.     

Vaccination with Leptospiral Outer Membrane Lipoprotein LipL32 Reduces Kidney Invasion of Leptospira interrogans Serovar Canicola in Hamsters

The Leptospira interrogans vaccines currently available are serovar specific and require regular booster immunizations to maintain protection of the host. In addition, a hamster challenge batch potency test is necessary to evaluate these vaccines prior to market release, requiring the use of a large number of animals, which is ethically and financially undesirable. Our previous work showed that the N terminus of the outer membrane protein LipL32 was altered in Leptospira interrogans serovar Canicola vaccines that fail the hamster challenge test, suggesting that it may be involved in the protective immune response. The aim of this study was to determine if vaccination with LipL32 protein alone could provide a protective response against challenge with L. interrogans serovar Canicola to hamsters. Recombinant LipL32, purified from an Escherichia coli expression system, was assessed for protective immunity in five groups of hamsters (n = 5) following a challenge with the virulent L. interrogans serovar Canicola strain Kito as a challenge strain. However, no significant survival against the L. interrogans serovar Canicola challenge was observed compared to that of unvaccinated negative controls. Subsequent histological analysis revealed reduced amounts of L. interrogans in the kidneys from the hamsters vaccinated with recombinant LipL32 protein prior to challenge; however, no significant survival against the L. interrogans serovar Canicola challenge was observed compared to that of unvaccinated negative controls. This finding corresponded to a noticeably reduced severity of renal lesions. This study provides evidence that LipL32 is involved in the protective response against L. interrogans serovar Canicola in hamsters and is the first reported link to LipL32-induced protection against kidney invasion.     

Safety in Numbers 7: veni,vidi, duci: A grounded theory evaluation of nursing students' medication dosage calculation problem-solving schemata construction

This paper evaluates nursing students' transition through schemata construction and competence development in medication dosage calculation problem-solving (MDC-PS). We advance a grounded theory from interview data that reflects the experiences and perceptions of two groups of undergraduate pre-registration nursing students: eight students exposed to a prototype authentic MDC-PS environment and didactic transmission methods of education and 15 final year students exposed to the safeMedicate authentic MDC-PS environment. We advance a theory of how classroom-based ‘chalk and talk’ didactic transmission environments offered multiple barriers to accurate MDC-PS schemata construction among novice students. While conversely it was universally perceived by all students that authentic learning and assessment environments enabled MDC-PS schemata construction through facilitating: ‘seeing’ the authentic features of medication dosage problems; context-based and situational learning; learning within a scaffolded environment that supported construction of cognitive links between the concrete world of clinical MDC-PS and the abstract world of mathematics; and confidence-building in their cognitive and functional competence ability. Drawing on the principle of veni, vidi, duci (I came, I saw, I calculated), we combined the two sets of evaluations to offer a grounded theoretical basis for schemata construction and competence development within this critical domain of professional practice.     

Safety in numbers 1: Essential numerical and scientific principles underpinning medication dose calculation

Registered nurses spend up to 40% of their professional clinical practice engaged in the art and science of medication dosage calculation problem-solving (MDC-PS). In advancing this patient safety critical discipline it is our position that as a profession we must first situate MDC-PS within the context of the wider features of the nursing numeracy, medicines management and clinical pharmacokinetic domains that inform its practice. This paper focuses on the essential relationship between numeracy, healthcare numeracy, medicines management, pharmacokinetics and MDC-PS. We present a taxonomy of generic numerical competencies for the pre-registration curriculum, with examples of essential medication dosage calculation requirements mapped to each skills domain. This is followed by a review of the symbols and measurement units that represent essential components of calculation competence in healthcare and medicines management practice. Finally we outline the fundamental pharmacokinetic knowledge that explains how the body deals with medication and we illustrate through clinical correlations why numeric and scientific knowledge and skills must be mastered to ensure safe dosage calculation and medicines management practice. The findings inform nurse education practice via advancing our understanding of a number of issues, including a unified taxonomy of generic numerical competencies mapped to the 42 revised UK Nursing and Midwifery Council (NMC) Essential Skills Clusters (NMC, 2010a; NMC, 2010b).     

The development of 24 polymorphic microsatellite loci for the endangered barred galaxias, Galaxias fuscus, through next generation DNA sequencing

Barred galaxias, Galaxias fuscus, is an endangered freshwater fish confined to headwaters of mountain streams in the Goulburn River system in central Victoria, Australia. Next generation DNA sequencing was used to develop a suite of microsatellite markers that can be used for future population genetic assessments of G. fuscus. A total of 24 polymorphic loci were identified and 12 characterized using 30 individuals from a single sample locale. We observed low to moderate genetic variation across most loci (mean number of alleles per locus?=?2.58; mean expected heterozygosity?=?0.37) with no evidence of individual loci deviating significantly from Hardy?CWeinberg equilibrium. Marker independence was confirmed with tests for linkage disequilibrium, and analyses indicated no evidence of null alleles across loci. The 12 markers characterized in the present study provide a valuable resource for future population genetic assessments and management of G. fuscus in Australia.     

How Many Radiographs Does It Take to Screen for Femoral Cam Morphology?: A Noninferiority Study

PurposeTo compare a 2-view radiograph series (AP of the pelvis and 45° Dunn of the hip) with a 5-view radiograph series for sensitivity in identifying femoral cam morphology.Materials and MethodsThis is a retrospective review of consecutive patients with a 5-view radiograph series (AP pelvis and AP, 45° Dunn, frog lateral, and false profile of the affected hip) from 2016 to 2017. Three fellowship trained radiologists blindly and independently evaluated 2 views (AP pelvis and Dunn) for a femoral cam lesion, acetabular rim calcification, Tonnis grade, and important incidental findings. Two weeks later, the same assessment was made on all 5 views. A noninferiority test of the 2-view series vs the 5-view series for sensitivity in identifying femoral cam morphology was conducted. Individual reader sensitivity calculations were performed and agreement was determined with the kappa statistic.ResultsThe 2-view series was noninferior to the 5-view series for cam identification (P value = 0.010). In comparing the 2-view vs 5-view series for individual readers, there was no difference in the sensitivities (84%-100% vs 85%-98%, P = 0.85-1.0) or specificities (11%-56% vs 7%-56%, P = 0.58-1.0) for cam identification. There was fair to excellent 2-view intrareader agreement (k = 0.38-0.93) and similar inter-reader agreement between the 2-view and 5-view (k = 0.33 vs 0.37).ConclusionsA 2-view radiograph series (AP pelvis and Dunn hip) is noninferior to a 5-view radiograph series for sensitivity in identifying femoral cam morphology.