BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Identification of promoter elements of parasitic nematodes in transgenic Caenorhabditis elegans

Transformation of the free-living nematode Caenorhabditis elegans with promoter/reporter gene constructs is a very powerful technique to examine and dissect gene regulatory mechanisms. No such transformation system is available for parasitic nematode species. We have exploited C. elegans as a heterologous transformation system to examine activity and specificity of parasitic nematode gene promoters. Using three different parasite promoter/lac Z reporter constructs strict tissue-specific expression is observed. Upstream sequences of the Haemonchus contortus gut pepsinogen gene pep-1 and cysteine protease gene AC-2 direct expression exclusively in gut cells, while promoter sequence of the Ostertagia circumcincta cuticular collagen gene colost-1 directs hypodermal-specific expression. Mutation analysis indicates that AC-2 promoter function is dependent on a GATA-like motif close to the translation start site, similar to our findings with the C.eleganscpr-1 cysteine protease gene. While the spatial expression of these parasite promoters in C. elegans correlates with their expression in the parasite, the exact timing of expression does not. This suggests that regulatory mechanisms influencing the timing of expression may have evolved more rapidly than those controlling spatial expression of structural genes

Stage-specific gene expression in Teladorsagia circumcincta (Nematoda : Strongylida) infective larvae and early parasitic stages

Suppression subtractive hybridisation was used to enrich genes expressed in a stage-specific manner in infective, exsheathed L3s (xL3) versus early L4s of the ovine nematode, Teladorsagia circumcincta prior to gene expression profiling by microarray. The 769 cDNA sequences obtained from the xL3-enriched library contained 361 unique sequences, with 292 expressed sequence tags (ESTs) being represented once ("singletons") and 69 sequences which were represented more than once (overlapping and non-overlapping "contigs"). The L4-enriched EST dataset contained 472 unique sequences, with 314 singletons and 158 contigs. Of these 833 sequences, 85% of the xL3 sequences and 86% of the L4 sequences exhibited homology to known genes or ESTs derived from other species of nematode. Quantitative differential expression (P &lt;0.05) was demonstrated for 563 (68%) of the ESTs by microarray. Within the U-specific dataset, more than 30% of the transcripts represented the enzyme, guanosine-5'-triphosphate (GTP)-cyclohydrolase, which is the first and rate-limiting enzyme of the tetrahydrobiopterin synthesis pathway and may be involved in critical elements of larval development. In L4s, proteolytic enzymes were highly up-regulated, as were collagens and a number of previously characterised secretory proteins, reflecting the rapid growth of these larvae in abomasal glands. (C) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.</p

Stage-specific gene expression in Teladorsagia circumcincta (Nematoda : Strongylida) infective larvae and early parasitic stages

Suppression subtractive hybridisation was used to enrich genes expressed in a stage-specific manner in infective, exsheathed L3s (xL3) versus early L4s of the ovine nematode, Teladorsagia circumcincta prior to gene expression profiling by microarray. The 769 cDNA sequences obtained from the xL3-enriched library contained 361 unique sequences, with 292 expressed sequence tags (ESTs) being represented once ("singletons") and 69 sequences which were represented more than once (overlapping and non-overlapping "contigs"). The L4-enriched EST dataset contained 472 unique sequences, with 314 singletons and 158 contigs. Of these 833 sequences, 85% of the xL3 sequences and 86% of the L4 sequences exhibited homology to known genes or ESTs derived from other species of nematode. Quantitative differential expression (P &lt;0.05) was demonstrated for 563 (68%) of the ESTs by microarray. Within the U-specific dataset, more than 30% of the transcripts represented the enzyme, guanosine-5'-triphosphate (GTP)-cyclohydrolase, which is the first and rate-limiting enzyme of the tetrahydrobiopterin synthesis pathway and may be involved in critical elements of larval development. In L4s, proteolytic enzymes were highly up-regulated, as were collagens and a number of previously characterised secretory proteins, reflecting the rapid growth of these larvae in abomasal glands. (C) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.</p

Use of Cold-Stored Whole Blood is Associated with Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood as part of the resuscitation of bleeding trauma patients. SUMMARY BACKGROUND DATA: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with whole blood (WB) emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective-observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score (ISS). All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included AKI, DVT/PE, pulmonary complications, and bleeding complications. RESULTS: A total of 1,623 (WB: 1,180(74%), BCT: 443(27%)) patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs. 0.83), more comorbidities, and more blunt MOI (all P\u3c0.05). After controlling for center, age, sex, MOI, and ISS, we found no differences in the rates of AKI, DVT/PE or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients (P\u3c0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients