A comparative evaluation of the efficacy between skeletal traction and skin traction in pre-operative management of femur shaft fractures in Korle Bu Teaching Hospital

Objectives: This study is to compare the outcomes of pre-operative skeletal and skin traction in adult femoral shaft fractures awaiting surgical fixation within two weeks of presentation to the Accident Center of Korle Bu Teaching Hospital.Methods: This study was a clinical trial on 86 recruited patients with closed femoral shaft fractures sustained within 24 hours of presentation grouped into 2 groups. Descriptive and inferential statistics comprising frequency, percentage, Chi-square, independent sample t-test and Mann-Whitney U test were used in analysing the data.Results: Of the total number of patients involved in the study, 74% (n=64) were males and 26% (n=22) were females with a mean age of 39.49 (SD ±15). There was no statistically significant difference in the mean visual analogue scale (VAS) pain assessment between the Skin traction group and Trans-tibia skeletal traction group after traction. With regards to complications, the difference between the Skin traction group and the Skeletal traction group was statistically significant (P=0.001). Moreover, the mean blood loss compared with the open type of reduction in the Transtibia skeletal traction group was significantly less than the Skin traction group (p=0.000).Conclusion: This study has shown that both Skeletal traction and Skin traction were equally effective in controlling pre-operative pain in adult patients with femoral shaft fractures and does not affect intra-operative blood loss and postoperative management. Therefore, pre-operative Skin traction can be considered a useful and cost-effective method of maintaining alignment and pain relief in adult femoral shaft fractures.Keywords: Skin traction, Trans-tibia skeletal, reamed Intramedullary nailing, Intra-operative blood loss, Visual Analogue ScaleFunding: Personal Fundin

Factors affecting early re-displacement of paediatric diaphyseal forearm fractures at Korle Bu Teaching Hospital

Background: Complete fractures of the forearm have the potential to displace and angulate with overriding fracture fragments. Maintaining acceptable reduction is not always possible, and re- displacement or re-angulation is the most commonly reported complication. Factors responsible for the re-displacement after an initial acceptable reduction have not been clearly defined. The study aimed to determine the factors that influence early re-displacement of paediatric diaphyseal forearm fractures in Korle-Bu Teaching Hospital.Methods: A prospective study in a cohort of 72 children below the age of 12 years with diaphyseal forearm fracture attending the Orthopaedic clinic were followed with close reduction casting from April 2017-December, 2017. Factors analysed included demographics, initial fracture features and the radiographic indices of the cast quality.Results: 93.1% (67) of the fractures were because of the children falling on an outstretched arm. Majority of the children had a fracture of the distal 1/3 of the radius (n=38, 52.6%). The overall C.I was 0.8 (SD 0.1). The only significant predictor for predicting re-displacement was children falling on an outstretched hand (p-value=0.0).Conclusion: This study has shown that the degree of initial displacement and the ability to achieve good reduction with a well moulded cast, constitute the major factors for early re-displacement of paediatric forearm fracturesKeywords: cast index, intermedullary nailing, elastic stable intramedullary nail, open reduction, internal fixationFunding: Personal fundin

Dynamics of crowded vesicle: local and global responses to membrane composition

The bacterial cell envelope is composed of a mixture of different lipids and proteins, making it an inherently complex organelle. The interactions between integral membrane proteins and lipids are crucial for their respective spatial localization within bacterial cells. We have employed microsecond timescale coarse-grained molecular dynamics simulations of vesicles of varying sizes and with a range of protein and lipid compositions, and used novel approaches to measure both local and global system dynamics, the latter based on spherical harmonics analysis. Our results suggest that both hydrophobic mismatch, enhanced by embedded membrane proteins, and curvature based sorting, due to different modes of undulation, may drive assembly in vesicular systems. Interestingly, the modes of undulation of the vesicles were found to be altered by the specific protein and lipid composition of the vesicle. Strikingly, lipid dynamics were shown to be coupled to proteins up to 6 nm from their surface, a substantially larger distance than has previously been observed, resulting in multi-layered annular rings enriched with particular types of phospholipid. Such large protein-lipid complexes may provide a mechanism for long-range communication. Given the complexity of bacterial membranes, our results suggest that subtle changes in lipid composition may have major implications for lipid and protein sorting under a curvature-based membrane-sorting model

Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial

Background: Fabry disease is frequently characterized by gastrointestinal symptoms, including diarrhea. Migalastat is an orally-administered small molecule approved to treat the symptoms of Fabry disease in patients with amenable mutations. Methods: We evaluated minimal clinically important differences (MCID) in diarrhea based on the corresponding domain of the patient-reported Gastrointestinal Symptom Rating Scale (GSRS) in patients with Fabry disease and amenable mutations (N = 50) treated with migalastat 150 mg every other day or placebo during the phase 3 FACETS trial (NCT00925301). Results: After 6 months, significantly more patients receiving migalastat versus placebo experienced improvement in diarrhea based on a MCID of 0.33 (43% vs 11%; p = .02), including the subset with baseline diarrhea (71% vs 20%; p = .02). A decline in kidney peritubular capillary globotriaosylceramide inclusions correlated with diarrhea improvement; patients with a reduction > 0.1 were 5.6 times more likely to have an improvement in diarrhea than those without (p = .031). Conclusions: Migalastat was associated with a clinically meaningful improvement in diarrhea in patients with Fabry disease and amenable mutations. Reductions in kidney globotriaosylceramide may be a useful surrogate endpoint to predict clinical benefit with migalastat in patients with Fabry disease. Trial registration NCT00925301; June 19, 2009

Molecular dynamics studies of transmembrane proteins within complex lipid environments

The interactions between lipids and proteins are crucial for many cellular processes. Typically, the nature of these interactions is studied in simple model lipid bilayers, which lack the complexity and heterogeneity of in vivo systems. Thus, this thesis investigates the impact of the lipid bilayer composition on protein dynamics and function. Both coarse grain and atomistic molecular dynamics simulations have been used to model membranes that contain lipid compositions approximating those found in vivo. The influence of these complex lipid environments on the dynamics of ?-helical and ?-barrel membrane protein is investigated. In particular, coarse grained simulations of a bilayer composed of a complex mixture of lipids, representing the Golgi apparatus, were used to identify preferential interactions of a helical transmembrane peptide with PIP2 lipids. Furthermore, atomistic molecular dynamics simulations have been used to identify several behaviour altering interactions between lipopolysaccharide, which is a key component of the Gram-negative bacterial outer membrane, and two outer membrane proteins, Hia and FecA. Lastly, coarse grained unilamellar vesicles, containing a complex mixture of phospholipids, were simulated in order to investigate protein aggregation and the short-term anomalous diffusion of lipids

Stability and membrane orientation of the fukutin transmembrane domain: a combined multiscale molecular dynamics and circular dichroism study

The N-terminal domain of Fukutin-I has been implicated in the localization of the protein in the endoplasmic reticulum/Golgi apparatus. It has been proposed to mediate this through its interaction with the thinner lipid bilayers found in these compartments. Here we have employed multi-scale molecular dynamics simulations and circular dichroism spectroscopy to explore the structure, stability and orientation of the short 36-residue N-terminal of Fukutin-I (FK1TMD) in lipids of differing tail lengths. Our results show that FK1TMD adopts a stable helical conformation in phosphatidylcholine lipids when orientated with its principal axis perpendicular to the bilayer plane. The stability of the helix is largely insensitive to the lipid tail length, avoiding hydrophobic mismatch by virtue of its mobility and ability to tilt within the lipid bilayers. This suggests that changes in FK1TMD tilt in response to bilayer properties may be implicated in the regulation of its trafficking. Coarse-grained simulations of the complex Golgi membrane suggest the N-terminal domain may induce the formation of microdomains in the surrounding membrane through its preferential interaction with 1,2-dipalmitoyl-sn-glycero-3-phoshpatidylinositol 4,5-bisphosphate (PIP2) lipids

Electroporation of the E. coli and S. Aureus membranes: molecular dynamics simulations of complex bacterial membranes

Bacterial membranes are complex organelles composed of a variety of lipid types. The differences in their composition are a key factor in determining their relative permeabilities. The success of antibacterial agents depends upon their interaction with bacterial membranes, yet little is known about the molecular-level interactions within membranes of different bacterial species. To address this, we have performed molecular dynamics simulations of two bacterial membranes: the outer membrane of E. coli and the cell membrane of S. aureus . We have retained the chemical complexity of the membranes by considering the details of their lipidic components. We identify the extended network of lipid-lipid interactions that stabilize the membranes. Our simulations of electroporation show that the S. aureus cell membrane is less resistant to poration than the E. coli outer membrane. The mechanisms of poration for the two membranes have subtle differences; for the E. coli outer membrane, relative differences in mobilities of the lipids of both leaflets are key in the process of poratio