What is the burden of illness in patients with reflux disease in South Africa?

Objectives: To describe the impact of heartburn on patients’ Health-Related Quality of Life (HRQL) in South Africa.Design: Survey of patient-reported outcomes and physician-assessed symptoms. Setting: South African, major referral gastroenterology clinic. Subjects: Consecutive patients with predominant symptoms of heartburn.Outcome measures:Patients completed the Afrikaans versions of the Gastrointestinal Symptom Rating Scale (GSRS), the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD) and the Short Form Health-36 (SF-36). Physician-assessed frequency and severity of heartburn during the previous 7 days were also recorded.Results: 125 patients with symptoms of heartburn (age: M=46.0 [±12 years]; females= 74%, 87% mixed race) completed the Afrikaans translation of GSRS, the QOLRAD and the Short-Form-36 (SF-36). Patients were bothered most by symptoms of reflux (mean GSRS score of 4.9, on a scale of 1 [not bothered] to 7 [very bothered]), indigestion (4.0) and abdominal pain (4.0). As a result of their symptoms, importantreflux related aspects of life, such as problems with food and drink (3.5), emotional distress (3.6), impaired vitality (3.7), sleep disturbance (3.8) and impaired physical/social functioning (4.3) were experienced (QOLRAD scores where 1 represents the most severe impact on daily functioning and 7 no impact). Overall HRQL measured by the SF-36 was poor across all domains and was significantly lower compared to the UK general population. Conclusions: There is consistentevidence that GERD symptoms substantially impair all aspects of HRQL in this mixed race South African population referred to this central clinic

The importance of comorbidity in analysing patient costs in Swedish primary care

BACKGROUND: The objective was to explore the usefulness of the morbidity risk adjustment system Adjusted Clinical Groups(® )(ACG), in comparison with age and gender, in explaining and estimating patient costs on an individual level in Swedish primary health care. Data were retrieved from two primary health care centres in southeastern Sweden. METHODS: A cross-sectional observational study. Data from electronic patient registers from the two centres were retrieved for 2001 and 2002, and patients were grouped into ACGs, expressing the individual combination of diagnoses and thus the comorbidity. Costs per patient were calculated for both years in both centres. Cost data from one centre were used to create ACG weights. These weights were then applied to patients at the other centre. Correlations between individual patient costs, age, gender and ACG weights were studied. Multiple linear regression analyses were performed in order to explain and estimate patient costs. RESULTS: The variation in individual patient costs was substantial within age groups as well as within ACG weight groups. About 37.7% of the individual patient costs could be explained by ACG weights, and age and gender added about 0.8%. The individual patient costs in 2001 estimated 22.0% of patient costs in 2002, whereas ACG weights estimated 14.3%. CONCLUSION: ACGs was an important factor in explaining and estimating individual patient costs in primary health care. Costs were explained to only a minor extent by age and gender. However, the usefulness of the ACG system appears to be sensitive to the accuracy of classification and coding of diagnoses by physicians

Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes: action LADA 9

Background: The study of endogenous insulin secretion may provide relevant insight into the comparison of the natural history of adult onset latent autoimmune diabetes (LADA) with types 1 and 2 diabetes mellitus. The aim of this study was to compare the results of the C-peptide response to mixed-meal stimulation in LADA patients with different disease durations and subjects with type 2 and adult-onset type 1 diabetes. Methods: Stimulated C-peptide secretion was assessed using the mixed-meal tolerance test in patients with LADA (n = 32), type 1 diabetes mellitus (n = 33) and type 2 diabetes mellitus (n = 30). All patients were 30 to 70 years old at disease onset. The duration of diabetes in all groups ranged from 6 months to 10 years. The recruitment strategy was predefined to include at least 10 subjects in the following 3 disease onset categories for each group: 6 to 18 months, 19 months to 5 years and 5 to 10 years. Results: At all time-points of the mixed-meal tolerance test, patients with LADA had a lower stimulated C-peptide response than the type 2 diabetes group and a higher response than the type 1 diabetes group. The same results were found when the peak or area under the C-peptide curve was measured. When the results were stratified by time since disease onset, a similar pattern of residual insulin secretory capacity was observed. Conclusions: The present study shows that the magnitude of stimulated insulin secretion in LADA is intermediate between that of type 1 and type 2 diabetes mellitus

Deletion of BmoR affects the expression of genes related to thiol/disulfide balance in Bacteroides fragilis

Bacteroides fragilis, an opportunistic pathogen and commensal bacterium in the gut, is one the most aerotolerant species among strict anaerobes. However, the mechanisms that control gene regulation in response to oxidative stress are not completely understood. In this study, we show that the MarR type regulator, BmoR, regulates the expression of genes involved in the homeostasis of intracellular redox state. Transcriptome analysis showed that absence of BmoR leads to altered expression in total of 167 genes. Sixteen of these genes had a 2-fold or greater change in their expression. Most of these genes are related to LPS biosynthesis and carbohydrates metabolism, but there was a signifcant increase in the expression of genes related to the redox balance inside the cell. A pyridine nucleotide-disulfde oxidoreductase located directly upstream of bmoR was shown to be repressed by direct binding of BmoR to the promoter region. The expression of two other genes, coding for a thiosulphate:quinoneoxidoreductase and a thioredoxin, are indirectly afected by bmoR mutation during oxygen exposure. Phenotypic assays showed that BmoR is important to maintain the thiol/disulfde balance in the cell, confrming its relevance to B. fragilis response to oxidative stress

Fixation of the fully hydroxyapatite-coated Corail stem implanted due to femoral neck fracture: 38 patients followed for 2 years with RSA and DEXA

Background Today, dislocated femoral neck fractures are commonly treated with a cemented hip arthroplasty. However, cementing of the femoral component may lead to adverse effects and even death. Uncemented stems may lower these risks and hydroxyapatite (HA) coating may enhance integration, but prosthetic stability and clinical outcome in patients with osteoporotic bone have not been fully explored. We therefore studied fixation and clinical outcome in patients who had had a femoral neck fracture and who had received a fully HA-coated stem prosthesis. Patients and methods 50 patients with a dislocated femoral neck fracture were operated with the fully HA-coated Corail total or hemiarthroplasty. 38 patients, mean age 81 (70-96) years, were followed for 24 months with conventional radiographs, RSA, DEXA, and for clinical outcome. Results 31 of the 38 implants moved statistically significantly up to 3 months, mainly distally, mean 2.7 mm (max. 20 mm (SD 4.3)), and rotated into retroversion mean 3.3 (-1.8 to 17) (SD 4.3) and then appeared to stabilize. Distal stem migration was more pronounced if the stem was deemed to be too small. There was no correlation between BMD and stem migration. The migration did not result in any clinically adverse effects. Interpretation The fully hydroxyapatite-coated Corail stem migrates during the first 3 months, but clinical outcome appears to be good, without any adverse events

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Application of Uncertainty Modeling Frameworks to Uncertain Isosurface Extraction

Abstract. Proper characterization of uncertainty is a challenging task. Depend-ing on the sources of uncertainty, various uncertainty modeling frameworks have been proposed and studied in the uncertainty quantification literature. This pa-per applies various uncertainty modeling frameworks, namely possibility theory, Dempster-Shafer theory and probability theory to isosurface extraction from un-certain scalar fields. It proposes an uncertainty-based marching cubes template as an abstraction of the conventional marching cubes algorithm with a flexible uncertainty measure. The applicability of the template is demonstrated using 2D simulation data in weather forecasting and computational fluid dynamics and a synthetic 3D dataset

Surface thermodynamic homeostasis of salivary conditioning films through polar–apolar layering

Salivary conditioning films (SCFs) form on all surfaces exposed to the oral cavity and control diverse oral surface phenomena. Oral chemotherapeutics and dietary components present perturbations to SCFs. Here we determine the surface energetics of SCFs through contact angle measurements with various liquids on SCFs following perturbations with a variety of chemotherapeutics as well as after renewed SCF formation. Sixteen-hour SCFs on polished enamel surfaces were treated with a variety of chemotherapeutics, including toothpastes and mouthrinses. After treatment with chemotherapeutics, a SCF was applied again for 3 h. Contact angles with four different liquids on untreated and treated SCF-coated enamel surfaces were measured and surface free energies were calculated. Perturbations either caused the SCF to become more polar or more apolar, but in all cases, renewed SCF formation compensated these changes. Thus, a polar SCF attracts different salivary proteins or adsorbs proteins in a different conformation to create a more apolar SCF surface after renewed SCF formation and vice versa for apolar SCFs. This polar–apolar layering in SCF formation presents a powerful mechanism in the oral cavity to maintain surface thermodynamic homeostasis—defining oral surface properties within a narrow, biological range and influencing chemotherapeutic strategies. Surface chemical changes brought about by dietary or chemotherapeutic perturbations to SCFs make it more polar or apolar, but new SCFs are rapidly formed compensating for changes in surface energetics

Biochemical and developmental characterization of carbonic anhydrase II from chicken erythrocytes

<p>Abstract</p> <p>Background</p> <p>Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes.</p> <p>Methods</p> <p>Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens.</p> <p>Results</p> <p>The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p < 0.01).</p> <p>Conclusions</p> <p>Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p < 0.01).</p