Clinical essentialising: a qualitative study of doctors’ medical and moral practice

While certain substantial moral dilemmas in health care have been given much attention, like abortion, euthanasia or gene testing, doctors rarely reflect on the moral implications of their daily clinical work. Yet, with its aim to help patients and relieve suffering, medicine is replete with moral decisions. In this qualitative study we analyse how doctors handle the moral aspects of everyday clinical practice. About one hundred consultations were observed, and interviews conducted with fifteen clinical doctors from different practices. It turned out that the doctors’ approach to clinical cases followed a rather strict pattern across specialities, which implied transforming patients’ diverse concerns into specific medical questions through a process of ‘essentialising’: Doctors broke the patient’s story down, concretised the patient’s complaints and categorised the symptoms into a medical sense. Patients’ existential meanings were removed, and the focus placed on the patients’ functioning. By essentialising, doctors were able to handle a complex and ambiguous reality, and establish a medically relevant problem. However, the process involved a moral as well as a practical simplification. Overlooking existential meanings and focusing on purely functional aspects of patients was an integral part of clinical practice and not an individual flaw. The study thus questions the value of addressing doctors’ conscious moral evaluations. Yet doctors should be aware that their daily clinical work systematically emphasises beneficence at the expense of others—that might be more important to the patient

Microsurgical third ventriculocisternostomy as an alternative to ETV: report of two cases

OBJECTIVE: To describe a microsurgical alternative to endoscopic third ventriculocisternostomy. METHODS: Two children with shunt-dependent hydrocephalus and multiple shunt revisions were considered candidates for third ventriculocisternostomy (TVS). Because of slit ventricles, an endoscopic approach was not possible and, therefore, both patients received a microsurgical TVS by a supraorbital approach. RESULTS: In both cases, microsurgical TVS was successful and the patients became shunt free. CONCLUSION: Microsurgical TVS by a supraorbital craniotomy is a viable alternative to endoscopic TVS in selected cases

Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions.

BACKGROUND: The physiological impairments most strongly associated with functional performance in older people are logically the most efficient therapeutic targets for exercise training interventions aimed at improving function and maintaining independence in later life. OBJECTIVES: The objectives of this review were to (1) systematically review the relationship between muscle power and functional performance in older people; (2) systematically review the effect of power training (PT) interventions on functional performance in older people; and (3) identify components of successful PT interventions relevant to pragmatic trials by scoping the literature. METHODS: Our approach involved three stages. First, we systematically reviewed evidence on the relationship between muscle power, muscle strength and functional performance and, second, we systematically reviewed PT intervention studies that included both muscle power and at least one index of functional performance as outcome measures. Finally, taking a strong pragmatic perspective, we conducted a scoping review of the PT evidence to identify the successful components of training interventions needed to provide a minimally effective training dose to improve physical function. RESULTS: Evidence from 44 studies revealed a positive association between muscle power and indices of physical function, and that muscle power is a marginally superior predictor of functional performance than muscle strength. Nine studies revealed maximal angular velocity of movement, an important component of muscle power, to be positively associated with functional performance and a better predictor of functional performance than muscle strength. We identified 31 PT studies, characterised by small sample sizes and incomplete reporting of interventions, resulting in less than one-in-five studies judged as having a low risk of bias. Thirteen studies compared traditional resistance training with PT, with ten studies reporting the superiority of PT for either muscle power or functional performance. Further studies demonstrated the efficacy of various methods of resistance and functional task PT on muscle power and functional performance, including low-load PT and low-volume interventions. CONCLUSIONS: Maximal intended movement velocity, low training load, simple training methods, low-volume training and low-frequency training were revealed as components offering potential for the development of a pragmatic intervention. Additionally, the research area is dominated by short-term interventions producing short-term gains with little consideration of the long-term maintenance of functional performance. We believe the area would benefit from larger and higher-quality studies and consideration of optimal long-term strategies to develop and maintain muscle power and physical function over years rather than weeks

Investigation of the Origin and Spread of a Mammalian Transposable Element Based on Current Sequence Diversity

Almost half the human genome consists of mobile DNA elements, and their analysis is a vital part of understanding the human genome as a whole. Many of these elements are ancient and have persisted in the genome for tens or hundreds of millions of years, providing a window into the evolution of modern mammals. The Golem family have been used as model transposons to highlight computational analyses which can be used to investigate these elements, particularly the use of molecular dating with large transposon families. Whole-genome searches found Golem sequences in 20 mammalian species. Golem A and B subsequences were only found in primates and squirrel. Interestingly, the full-length Golem, found as a few copies in many mammalian genomes, was found abundantly in horse. A phylogenetic profile suggested that Golem originated after the eutherian–metatherian divergence and that the A and B subfamilies originated at a much later date. Molecular dating based on sequence diversity suggests an early age, of 175 Mya, for the origin of the family and that the A and B lineages originated much earlier than expected from their current taxonomic distribution and have subsequently been lost in some lineages. Using publically available data, it is possible to investigate the evolutionary history of transposon families. Determining in which organisms a transposon can be found is often used to date the origin and expansion of the families. However, in this analysis, molecular dating, commonly used for determining the age of gene sequences, has been used, reducing the likelihood of errors from deleted lineages

Maroon Archaeology Beyond the Americas: A View From Kenya

Archaeological research on Maroons—that is, runaway slaves—has been largely confined to the Americas. This essay advocates a more global approach. It specifically uses two runaway slave communities in 19th-century coastal Kenya to rethink prominent interpretive themes in the field, including “Africanisms,” Maroons’ connections to indigenous groups, and Maroon group cohesion and identity. This article’s analysis demonstrates that the comparisons enabled by a more globalized perspective benefit the field. Instead of eliding historical and cultural context, these comparisons support the development of more localized and historically specific understandings of individual runaway slave communities both in Kenya and throughout the New World

Assessing the Value of DNA Barcodes and Other Priority Gene Regions for Molecular Phylogenetics of Lepidoptera

BACKGROUND: Despite apparently abundant amounts of observable variation and species diversity, the order Lepidoptera exhibits a morphological homogeneity that has provided only a limited number of taxonomic characters and led to widespread use of nucleotides for inferring relationships. This study aims to characterize and develop methods to quantify the value of priority gene regions designated for Lepidoptera molecular systematics. In particular, I assess how the DNA barcode segment of the mitochondrial COI gene performs across a broad temporal range given its number one position of priority, most sequenced status, and the conflicting opinions on its phylogenetic performance. METHODOLOGY/PRINCIPAL FINDINGS: Gene regions commonly sequenced for lepidoptera phylogenetics were scored using multiple measures across three categories: practicality, which includes universality of primers and sequence quality; phylogenetic utility; and phylogenetic signal. I found that alternative measures within a category often appeared correlated, but high scores in one category did not necessarily translate into high scores in another. The DNA barcode was easier to sequence than other genes, and had high scores for utility but low signal above the genus level. CONCLUSIONS/SIGNIFICANCE: Given limited financial resources and time constraints, careful selection of gene regions for molecular phylogenetics is crucial to avoid wasted effort producing partially informative data. This study introduces an approach to assessing the value of gene regions prior to the initiation of new studies and presents empirical results to help guide future selections

TRAM (Transcriptome Mapper): database-driven creation and analysis of transcriptome maps from multiple sources

<p>Abstract</p> <p>Background</p> <p>Several tools have been developed to perform global gene expression profile data analysis, to search for specific chromosomal regions whose features meet defined criteria as well as to study neighbouring gene expression. However, most of these tools are tailored for a specific use in a particular context (e.g. they are species-specific, or limited to a particular data format) and they typically accept only gene lists as input.</p> <p>Results</p> <p>TRAM (Transcriptome Mapper) is a new general tool that allows the simple generation and analysis of quantitative transcriptome maps, starting from any source listing gene expression values for a given gene set (e.g. expression microarrays), implemented as a relational database. It includes a parser able to assign univocal and updated gene symbols to gene identifiers from different data sources. Moreover, TRAM is able to perform intra-sample and inter-sample data normalization, including an original variant of quantile normalization (scaled quantile), useful to normalize data from platforms with highly different numbers of investigated genes. When in 'Map' mode, the software generates a quantitative representation of the transcriptome of a sample (or of a pool of samples) and identifies if segments of defined lengths are over/under-expressed compared to the desired threshold. When in 'Cluster' mode, the software searches for a set of over/under-expressed consecutive genes. Statistical significance for all results is calculated with respect to genes localized on the same chromosome or to all genome genes. Transcriptome maps, showing differential expression between two sample groups, relative to two different biological conditions, may be easily generated. We present the results of a biological model test, based on a meta-analysis comparison between a sample pool of human CD34+ hematopoietic progenitor cells and a sample pool of megakaryocytic cells. Biologically relevant chromosomal segments and gene clusters with differential expression during the differentiation toward megakaryocyte were identified.</p> <p>Conclusions</p> <p>TRAM is designed to create, and statistically analyze, quantitative transcriptome maps, based on gene expression data from multiple sources. The release includes FileMaker Pro database management runtime application and it is freely available at <url>http://apollo11.isto.unibo.it/software/</url>, along with preconfigured implementations for mapping of human, mouse and zebrafish transcriptomes.</p

Shotgun sequencing of Yersinia enterocolitica strain W22703 (biotype 2, serotype O:9): genomic evidence for oscillation between invertebrates and mammals

<p>Abstract</p> <p>Background</p> <p><it>Yersinia enterocolitica </it>strains responsible for mild gastroenteritis in humans are very diverse with respect to their metabolic and virulence properties. Strain W22703 (biotype 2, serotype O:9) was recently identified to possess nematocidal and insecticidal activity. To better understand the relationship between pathogenicity towards insects and humans, we compared the W22703 genome with that of the highly pathogenic strain 8081 (biotype1B; serotype O:8), the only <it>Y. enterocolitica </it>strain sequenced so far.</p> <p>Results</p> <p>We used whole-genome shotgun data to assemble, annotate and analyse the sequence of strain W22703. Numerous factors assumed to contribute to enteric survival and pathogenesis, among them osmoregulated periplasmic glucan, hydrogenases, cobalamin-dependent pathways, iron uptake systems and the <it>Yersinia </it>genome island 1 (YGI-1) involved in tight adherence were identified to be common to the 8081 and W22703 genomes. However, sets of ~550 genes revealed to be specific for each of them in comparison to the other strain. The plasticity zone (PZ) of 142 kb in the W22703 genome carries an ancient flagellar cluster Flg-2 of ~40 kb, but it lacks the pathogenicity island YAPI_Ye, the secretion system <it>ysa </it>and <it>yts1</it>, and other virulence determinants of the 8081 PZ. Its composition underlines the prominent variability of this genome region and demonstrates its contribution to the higher pathogenicity of biotype 1B strains with respect to W22703. A novel type three secretion system of mosaic structure was found in the genome of W22703 that is absent in the sequenced strains of the human pathogenic <it>Yersinia </it>species, but conserved in the genomes of the apathogenic species. We identified several regions of differences in W22703 that mainly code for transporters, regulators, metabolic pathways, and defence factors.</p> <p>Conclusion</p> <p>The W22703 sequence analysis revealed a genome composition distinct from other pathogenic <it>Yersinia enterocolitica </it>strains, thus contributing novel data to the <it>Y. enterocolitica </it>pan-genome. This study also sheds further light on the strategies of this pathogen to cope with its environments.</p

Meningitic Escherichia coli K1 Penetration and Neutrophil Transmigration Across the Blood–Brain Barrier are Modulated by Alpha7 Nicotinic Receptor

Alpha7 nicotinic acetylcholine receptor (nAChR), an essential regulator of inflammation, is abundantly expressed in hippocampal neurons, which are vulnerable to bacterial meningitis. However, it is unknown whether α7 nAChR contributes to the regulation of these events. In this report, an aggravating role of α7 nAChR in host defense against meningitic E. coli infection was demonstrated by using α7-deficient (α7-/-) mouse brain microvascular endothelial cells (BMEC) and animal model systems. As shown in our in vitro and in vivo studies, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the blood-brain barrier (BBB) were significantly reduced in α7-/- BMEC and α7-/- mice. Stimulation by nicotine was abolished in the α7-/- cells and animals. The same blocking effect was achieved by methyllycaconitine (α7 antagonist). The tight junction molecules occludin and ZO-1 were significantly reduced in the brain cortex of wildtype mice infected with E. coli and treated with nicotine, compared to α7-/- cells and animals. Decreased neuronal injury in the hippocampal dentate gyrus was observed in α7-/- mice with meningitis. Proinflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1, MIP-1alpha, and RANTES) and adhesion molecules (CD44 and ICAM-1) were significantly reduced in the cerebrospinal fluids of the α7-/- mice with E. coli meningitis. Furthermore, α7 nAChR is the major calcium channel for nicotine- and E. coli K1-increased intracellular calcium concentrations of mouse BMEC. Taken together, our data suggest that α7 nAChR plays a detrimental role in the host defense against meningitic infection by modulation of pathogen invasion, PMN recruitment, calcium signaling and neuronal inflammation

Effectiveness of dual-task functional power training for preventing falls in older people: Study protocol for a cluster randomised controlled trial

Background: Falls are a major public health concern with at least one third of people aged 65 years and over falling at least once per year, and half of these will fall repeatedly, which can lead to injury, pain, loss of function and independence, reduced quality of life and even death. Although the causes of falls are varied and complex, the age-related loss in muscle power has emerged as a useful predictor of disability and falls in older people. In this population, the requirements to produce explosive and rapid movements often occurs whilst simultaneously performing other attention-demanding cognitive or motor tasks, such as walking while talking or carrying an object. The primary aim of this study is to determine whether dual-task functional power training (DT-FPT) can reduce the rate of falls in community-dwelling older people. Methods/Design: The study design is an 18-month cluster randomised controlled trial in which 280 adults aged =65 years residing in retirement villages, who are at increased risk of falling, will be randomly allocated to: 1) an exercise programme involving DT-FPT, or 2) a usual care control group. The intervention is divided into 3 distinct phases: 6 months of supervised DT-FPT, a 6-month 'step down' maintenance programme, and a 6-month follow-up. The primary outcome will be the number of falls after 6, 12 and 18 months. Secondary outcomes will include: lower extremity muscle power and strength, grip strength, functional assessments of gait, reaction time and dynamic balance under single- and dual-task conditions, activities of daily living, quality of life, cognitive function and falls-related self-efficacy. We will also evaluate the cost-effectiveness of the programme for preventing falls. Discussion: The study offers a novel approach that may guide the development and implementation of future community-based falls prevention programmes that specifically focus on optimising muscle power and dual-task performance to reduce falls risk under 'real life' conditions in older adults. In addition, the 'step down' programme will provide new information about the efficacy of a less intensive maintenance programme for reducing the risk of falls over an extended period. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613001161718. Date registered 23 October 2013