Anophthalmia and microphthalmia

Anophthalmia and microphthalmia describe, respectively, the absence of an eye and the presence of a small eye within the orbit. The combined birth prevalence of these conditions is up to 30 per 100,000 population, with microphthalmia reported in up to 11% of blind children. High-resolution cranial imaging, post-mortem examination and genetic studies suggest that these conditions represent a phenotypic continuum. Both anophthalmia and microphthalmia may occur in isolation or as part of a syndrome, as in one-third of cases. Anophthalmia/microphthalmia have complex aetiology with chromosomal, monogenic and environmental causes identified. Chromosomal duplications, deletions and translocations are implicated. Of monogenic causes only SOX2 has been identified as a major causative gene. Other linked genes include PAX6, OTX2, CHX10 and RAX. SOX2 and PAX6 mutations may act through causing lens induction failure. FOXE3 mutations, associated with lens agenesis, have been observed in a few microphthalmic patients. OTX2, CHX10 and RAX have retinal expression and may result in anophthalmia/microphthalmia through failure of retinal differentiation. Environmental factors also play a contributory role. The strongest evidence appears to be with gestational-acquired infections, but may also include maternal vitamin A deficiency, exposure to X-rays, solvent misuse and thalidomide exposure. Diagnosis can be made pre- and post-natally using a combination of clinical features, imaging (ultrasonography and CT/MR scanning) and genetic analysis. Genetic counselling can be challenging due to the extensive range of genes responsible and wide variation in phenotypic expression. Appropriate counselling is indicated if the mode of inheritance can be identified. Differential diagnoses include cryptophthalmos, cyclopia and synophthalmia, and congenital cystic eye. Patients are often managed within multi-disciplinary teams consisting of ophthalmologists, paediatricians and/or clinical geneticists, especially for syndromic cases. Treatment is directed towards maximising existing vision and improving cosmesis through simultaneous stimulation of both soft tissue and bony orbital growth. Mild to moderate microphthalmia is managed conservatively with conformers. Severe microphthalmia and anophthalmia rely upon additional remodelling strategies of endo-orbital volume replacement (with implants, expanders and dermis-fat grafts) and soft tissue reconstruction. The potential for visual development in microphthalmic patients is dependent upon retinal development and other ocular characteristics

Prehospital critical care is associated with increased survival in adult trauma patients in Scotland

Background Scotland has three prehospital critical care teams (PHCCTs) providing enhanced care support to a usually paramedic-delivered ambulance service. The effect of the PHCCTs on patient survival following trauma in Scotland is not currently known nationally. Methods National registry-based retrospective cohort study using 2011-2016 data from the Scottish Trauma Audit Group. 30-day mortality was compared between groups after multivariate analysis to account for confounding variables. Results Our data set comprised 17 157 patients, with a mean age of 54.7 years and 8206 (57.5%) of male gender. 2877 patients in the registry were excluded due to incomplete data on their level of prehospital care, leaving an eligible group of 14 280. 13 504 injured adults who received care from ambulance clinicians (paramedics or technicians) were compared with 776 whose care included input from a PHCCT. The median Injury Severity Score (ISS) across all eligible patients was 9; 3076 patients (21.5%) met the ISS>15 criterion for major trauma. Patients in the PHCCT cohort were statistically significantly (all p < 0.01) more likely to be male; be transported to a prospective Major Trauma Centre; have suffered major trauma; have suffered a severe head injury; be transported by air and be intubated prior to arrival in hospital. Following multivariate analysis, the OR for 30-day mortality for patients seen by a PHCCT was 0.56 (95% CI 0.36 to 0.86, p=0.01). Conclusion Prehospital care provided by a physician-led critical care team was associated with an increased chance of survival at 30 days when compared with care provided by ambulance clinicians

Expression of Bovine Interleukin-1β in a Bovine Herpesvirus-1 Vector:In VitroAnalysis

AbstractIn order to evaluate whether bovine herpesvirus-1 (BHV-1) could be used as a live viral vector for the expression of cytokines, we constructed a recombinant BHV-1 expressing bovine interleukin-1β (boIL-1β). The boIL-1β coding sequence, corresponding to the cleaved mature product, was fused with the BHV-1 glycoprotein C (gC) signal peptide sequence; the resultant gC-boIL-1β fusion gene was recombined into the gC locus of the BHV-1 genome. Southern blot analysis confirmed the proper genomic configuration of the recombinant virus. Results from transcript analysis showed that boIL-1β was expressed in infected cells with kinetics similar to that of gC. Indirect immunofluorescence and immunoprecipitation assays showed that the recombinant protein was produced in both cell-associated and secreted forms. Western blot analysis detected a 19.3-kDa protein. Further analysis, using an IL-1β bioassay demonstrated that both the cellular and secreted forms of recombinant boIL-1β possessed biological activity. The expression of the boIL-1β protein did not affect thein vitrogrowth efficiency of the virus, which exhibited similar growth kinetics to that of a simple gC deletion mutant. The results from this study demonstrate that BHV-1 can be used to express a functional cytokine, thereby establishing the basis to further study recombinant BHV-1 expressing cytokines as an alternative means to attenuate the virus and also as a potentialin situcytokine delivery system to modulate immune responses against BHV-1 and other cattle pathogens

Are some teat disinfectant formulations more effective against specific bacteria isolated on teat skin than others?

peer-reviewedThe use of pre- and post-milking teat disinfectants can reduce teat bacterial load and aid in the collection of high-quality milk. The objective of this study was to compare the reduction in bacteria populations on teat skin after the application of different commercial teat disinfectant products. Ten teat disinfectant products were applied to the teats of 10 Holstein–Friesian cows. One cow received one teat disinfectant product at each sampling point before cluster application for milking. A composite swab sample was taken of the 4 teats of each cow before and after teat disinfectant application. Swab samples were placed on three different selective agars to enumerate bacterial counts of staphylococcal, streptococcal and coliforms isolates on teat skin. Staphylococcal isolates were the most prominent bacterial group recovered on teat swabs (49%), followed by streptococcal (36%) and coliform (15%) isolates before the application of disinfectant. The average bacterial reductions on teat skin were shown to be 76%, 73% and 60% for staphylococcal, streptococcal and coliform isolates, respectively. All of the teat disinfectant products tested reduced teat bacterial load for all three bacterial groups. Product 4 containing 0.6% w/w diamine was the most effective against bacterial populations of staphylococcal and streptococcal isolates on teat skin with a reduction of 90% and 94%, respectively. Whereas product 10, which contained 0.5% w/w iodine, resulted in the highest reduction in coliforms on teat skin with a reduction of 91%. Results from this study suggest that specific bacterial population loads on teats can be reduced using different teat disinfectant formulations

Alpha Band Signatures of Social Synchrony

Previous research has reported changes in mu rhythm, the central rhythm of the alpha frequency band, in both intentional and spontaneous interpersonal coordination. The current study was designed to extend existing findings on social synchrony to the pendulum swinging task and simultaneously measured time unfolding behavioral synchrony and EEG estimation of mu activity during spontaneous, intentional in-phase and intentional anti-phase interpersonal coordination. As expected, the behavioral measures of synchrony demonstrated the expected pattern of weak synchronization for spontaneous coordination, moderate synchronization for intentional anti-phase coordination, and strong synchronization for in-phase coordination. With respect to the EEG measures, we found evidence for mu enhancement for spontaneous coordination in contrast to mu suppression for intentional coordination (both in phase and anti-phase), with higher levels of synchronization associated with higher levels of mu suppression in the right hemisphere. The implications of the research findings and methodology for understanding the underlying mechanisms contributing to social problems in psychological disorders, leader-follower relationships, and inter-brain dynamics are discussed

The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement

Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe

Clinical effectiveness and cost-effectiveness of open and arthroscopic rotator cuff repair [the UK Rotator Cuff Surgery (UKUFF) randomised trial]

Peer reviewedPublisher PD

Bacillus Coagulans GBI-30 (BC30) improves indices of Clostridium difficile-Induced colitis in mice

<p>Abstract</p> <p>Background</p> <p>Probiotics have beneficial effects in rodent models of <it>Clostridium difficile </it>(<it>C. diffiicle</it>)-induced colitis. The spore forming probiotic strain <it>Bacillus Coagulans </it>GBI-30, 6086 (BC30) has demonstrated anti-inflammatory and immune-modulating effects <it>in vitro</it>. Our goal was to determine if BC30 improved <it>C. difficile</it>-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline) or BC30 (2 × 10⁹CFU per day). Mice in the <it>C. difficile </it>groups received an antibiotic mixture (study days 5 to 8 in the drinking water), and clindamycin (10 mg/kg, i.p., on study day 10). The <it>C. difficile </it>strain VPI 10463 was given by gavage at 10⁴CFU to induce colitis on day 11. On day 16, stools and colons were collected for further analyses.</p> <p>Results</p> <p>All mice treated with BC30 survived on study day 13, while two mice treated with vehicle did not survive. On day 12, a significant difference (p = 0.0002) in the percentage of mice with normal stools (66.7%) was found in the BC30/<it>C. difficile </it>group, as compared to the vehicle/<it>C. diffcile </it>group (13.0%). On study day 16, 23.8% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0187). On this day, the stool consistency score for the BC30/<it>C. difficile </it>group (1.1 ± 0.2) was significantly lower (p < 0.05) than for the vehicle/<it>C. difficile </it>cohort (1.9 ± 0.2). BC30 modestly attenuated the colonic pathology (crypt damage, edema, leukocyte influx) that was present following <it>C. difficile infection</it>. Colonic MIP-2 chemokine contents (pg/2 cm colon) were: 10.2 ± 0.5 (vehicle/no <it>C. difficile</it>), 24.6 ± 9.5 (vehicle/<it>C. difficile</it>) and 16.3 ± 4.3 (BC30/<it>C. difficle</it>).</p> <p>Conclusion</p> <p>The probiotic BC30 improved some parameters of <it>C. difficile</it>-induced colitis in mice. BC30 prolonged the survival of <it>C. diffiicle </it>infected mice. Particularly, this probiotic improved the stool consistency of mice, in this infectious colitis model.</p

Contributions of the RhoGEF activity of p210 BCR/ABL to disease progression

We have previously identified a tyrosine kinase-independent, guanine nucleotide exchange factor (GEF) activity that is contained within the region of p210 BCR/ABL that distinguishes it from p190 BCR/ABL. In the current study we have compared the transforming activity of p190 BCR/ABL, p210 BCR/ABL, and a mutant that lacks GEF activity (p210 BCR/ABL(S509A)). In cell-based, ex vivo, and murine bone marrow transplantation assays (BMT) the transforming activity of p210 BCR/ABL(S509A) mimics p190 BCR/ABL, and is distinct from p210 BCR/ABL. Thus, in the BMT assay, the p190 BCR/ABL and p210 BCR/ABL(S509A) transplanted mice exhibit a more rapid onset of disease than mice transplanted with p210 BCR/ABL. The reduced disease latency is associated with erythroid hyperplasia in the absence of anemia, and expansion of the MEP, CMP and GMP populations, producing a phenotype that is similar to acute myeloid leukemia (AML-M6). The disease phenotype is readily transplantable into secondary recipients. This is consistent with ex vivo clonogenicity assays where p210 BCR/ABL preferentially supports the growth of CFU-GM, while p190 BCR/ABL and the mutant preferentially support the growth of BFU-E. These results suggest that the GEF activity that distinguishes p210 BCR/ABL from p190 BCR/ABL actively regulates disease progression