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Background: Diabetes is one of the most prevalent and costly chronic diseases in the United States., Objectives: To analyze the risk of developing diabetes and the annual cost of diabetes for a US general population., Methods: Data from the Medical Expenditure Panel Survey, 2008 to 2012, were used to analyze 1) probabilities of developing diabetes and 2) annual total health care expenditures for diabetics. The age-, sex-, race-, and body mass index (BMI)-specific risks of developing diabetes were estimated by fitting an exponential survival function to age at first diabetes diagnosis. Annual health care expenditures were estimated using a generalized linear model with log-link and gamma variance function. Complex sampling designs in the Medical Expenditure Panel Survey were adjusted for. All dollar values are presented in 2012 US dollars., Results: We observed a more than 6 times increase in diabetes risks for class III obese (BMI ≥ 40 kg/m 2 ) individuals compared with normal-weight individuals. Using age 50 years as an example, we found a more than 3 times increase in annual health care expenditures for those with diabetes ($13,581) compared with those without diabetes ($3,954). Compared with normal-weight (18.5 ≤ BMI < 25 kg/m 2 ) individuals, class II obese (35 ≤ BMI < 40 kg/m 2 ) and class III obese (BMI ≥ 40 kg/m 2 ) individuals incurred an annual marginal cost of $628 and $756, respectively. The annual health care expenditure differentials between those with and without diabetes of age 50 years were the highest for individuals with class II ($12,907) and class III ($9,703) obesity., Conclusions: This article highlights the importance of obesity on diabetes burden. Our results suggested that obesity, in particular, class II and class III (i.e., BMI ≥ 35 kg/m 2 ) obesity, is associated with a substantial increase in the risk of developing diabetes and imposes a large economic burden., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

The cattle tick, Rhipicephalus (Boophilus) microplus, is a pest which causes multiple health complications in cattle. The G protein-coupled receptor (GPCR) super-family presents a candidate target for developing novel tick control methods. However, GPCRs share limited sequence similarity among orthologous family members, and there is no reference genome available for R. microplus. This limits the effectiveness of alignment-dependent methods such as BLAST and Pfam for identifying GPCRs from R. microplus. However, GPCRs share a common structure consisting of seven transmembrane helices. We present an analysis of the R. microplus synganglion transcriptome using a combination of structurally-based and alignment-free methods which supplement the identification of GPCRs by sequence similarity. TMHMM predicts the number of transmembrane helices in a protein sequence. GPCRpred is a support vector machine-based method developed to predict and classify GPCRs using the dipeptide composition of a query amino acid sequence. These two bioinformatic tools were applied to our transcriptome assembly of the cattle tick synganglion. Together, BLAST and Pfam identified 85 unique contigs as encoding partial or full length candidate cattle tick GPCRs. Collectively, TMHMM and GPCRpred identified 27 additional GPCR candidates that BLAST and Pfam missed. This demonstrates that the addition of structurally-based and alignment-free bioinformatic approaches to transcriptome annotation and analysis produces a greater collection of prospective GPCRs than an analysis based solely upon methodologies dependent upon sequence alignment and similarity., (Published by Elsevier GmbH.)

Background: Chronic obstructive pulmonary disease (COPD) is a common disease worldwide with significant morbidity and mortality., Aim: To investigate the effect of a comprehensive COPD management programme in decreasing COPD readmissions 1 year before and 1 year after the programme., Method: 185 (166 males) patients admitted for acute exacerbation of COPD (AECOPD) were recruited between September 2010 and December 2012. COPD care team provided crisis support and maintenance therapy for the COPD patients for a total of 16 weeks. The protocol included COPD clinic run by respiratory physicians, COPD education and nurse clinics by respiratory nurses, out-patient pulmonary rehabilitation programme by physiotherapists, fast track doctor's clinic, telephone hotline for patients and nurse telephone calls to patients. Readmissions over a period of 1 year were assessed., Results: The mean (SD) age of the subjects and FEV1 % predicted normal were 76.9 ± 7.37 yrs and 44.4 ± 20.7% respectively. 40 (21.6%) patients required non-invasive positive pressure ventilation during the recruitment admission. Admissions for AECOPD decreased from 2.39 ± 2.05 one year before programme to 1.65 ± 2.1 one year after programme (mean difference 0.75 ± 2.11 episodes, p < 0.001). The length of hospital stay was reduced from 12.17 ± 9.14 days one year before programme to 9.09 ± 12.1 days one year after the programme (mean difference 3.09 ± 12.1 days, p < 0.001). The FEV1 percentage predicted and quality of life measured by St George's Respiratory Questionnaire showed no significant improvement at 16 weeks after recruitment into the programme as compared to at 6 weeks., Conclusion: COPD care programme is effective in decreasing readmissions and length of hospital day for COPD patients.

A major challenge in the field of transplantation is to prevent graft rejection and prolong graft survival. Tolerance induction is a promising way to achieve long-term graft survival without the need for potent immunosuppression and its associated side effects. The recent success of co-stimulatory blockade by the chimeric protein CTLA4Ig in the modulation of the recipient's immune system and the prolongation of graft survival in animal models suggests a possible application of CTLA4Ig in clinical transplantation. To produce sufficient amounts of CTLA4Ig for future clinical application, we sought to use the mammary gland as a bioreactor and produce CTLA4Ig in the milk of transgenic farm animals. Prior to the generation of transgenic farm animals, we tested our strategy in mice. Using the promoter of the sheep beta-lactoglobulin gene, we expressed our CTLA4Ig chimeric gene in the mammary gland of transgenic mice. The yield of CTLA4Ig was fivefold higher in transgenic milk than that from transfected cells. Purified milk-derived CTLA4Ig is biologically active and suppresses T cell activation. We showed that the production of CTLA4Ig in the milk has no adverse immunosuppression effect on the transgenic animals and the offsprings that were fed with the transgenic milk. The findings suggest that the approach to produce CTLA4Ig in milk by transgenesis is feasible; further studies involving farm animals are warranted.

An efficient algorithm is described for finding matches, repeats and other word relations, allowing for errors, in large data sets of long molecular sequences. The algorithm entails hashing on fixed-size words in conjunction with the use of a linked list connecting all occurrences of the same word. The average memory and run time requirement both increase almost linearly with the total sequence length. Some results of the program's performance on a database of Escherichia coli DNA sequences are presented.