Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP(5) glycoprotein and improves immune response in challenged pigs

Pigs exposed to GP(5) protein of PRRSV by means of DNA immunization develop specific neutralizing and protecting antibodies. Herein, we report on the consequences of codon bias, and on the favorable outcome of the systematic replacement of native codons of PRRSV ORF5 gene with codons chosen to reflect more closely the codon preference of highly expressed mammalian genes. Therefore, a synthetic PRRSV ORF5 gene (synORF5) was constructed in which 134 nucleotide substitutions were made in comparison to wild-type gene (wtORF5), such that 59% (119) of wild-type codons were replaced with known preferable codons in mammalian cells. In vitro expression in mammalian cells of synORF5 was considerably increased comparatively to wtORF5, following infection with tetracycline inducible replication-defective human adenoviral vectors (hAdVs). After challenge inoculation, SPF pigs vaccinated twice with recombinant hAdV/synORF5 developed earlier and higher antibody titers, including virus neutralizing antibodies to GP(5) than pigs vaccinated with hAdV/wtORF5. Data obtained from animal inoculation studies suggest direct correlation between expression levels of immunogenic structural viral proteins and immune response.     

In the wake of Hurricane Isabel: a prospective study of postevent trauma and injury control strategies

Preventing hurricane-related injuries (HRI) has historically centered on the pre-event and event phases of the disaster. To date, no study has focused on injuries occurring during the postevent phase. We examined HRI that occurred after Hurricane Isabel struck a U.S. urban city. HRI presenting 1 week prior to the hurricane were collected from emergency department electronic records. HRI that presented to our level 1 trauma center were prospectively collected for 1 week after the hurricane. Nine hundred seventy-eight patients with possible HRI were identified. Fifty-one patients with trauma directly attributed to the hurricane were used for analysis. The number of HRI occurring before, during, and after the hurricane were 7 (14%), 3 (6%), and 41 (80%), respectively. The majority of HRI (37%) occurred on posthurricane day 1. Head, chest, upper and lower extremities accounted for 9 (18%), 8 (16%), 13 (26%), and 14 (28%) of HRI. More than one third of HRI patients were admitted to the hospital, and 12 (24%) underwent an operation. The average hospital length of stay was 4.7 days. Of our trauma alerts, 75 per cent had an Injury Severity Score (ISS) >8, and 20 per cent had an ISS >15. Tree-related injuries (TRI) accounted for 59 per cent of HRI. Males, ages 50-60, had the highest incidence of injury (63%). Significant injuries occur in the wake of a hurricane. Optimization of disaster preparation must include prevention strategies targeted to the postevent recovery phase of disasters.     

Treatment outcomes of unstable proximal phalangeal head fractures of the finger in children

The authors reviewed 37 children presenting with closed, unstable fractures of the proximal phalangeal head. Fractures were classified as intra-articular (n = 15), including 14 unicondylar and 1 bicondylar, or extra-articular (n = 22), including 20 subcondylar and 2 comminuted subcondylar. Eighteen patients underwent closed reduction with K-wire fixation (n = 11) or dynamic skeletal traction (n = 7). Nineteen patients underwent open reduction with K-wire fixation (n = 14) or miniscrews (n = 5). Results were considered excellent when the active range of motion (ROM) of the proximal interphalangeal joint was > or = 90 degrees (n = 26); fair, active ROM, 70 to 89 degrees (n = 6); and poor, active ROM < 70 degrees (n = 5). The intra-articular fractures were rated 9 excellent, 5 fair, and 1 poor. The extra-articular fractures were rated 17 excellent, 1 fair, and 4 poor. The 18 closed reductions, K-wire fixation (n = 11) and traction (n = 7), were rated 16 excellent and 2 fair. The 19 open reductions, K-wire fixation (n = 14) and miniscrew fixation (n = 5), were rated 10 excellent, 4 fair, and 5 poor. Closed reduction showed better results than open reduction. Dynamic skeletal traction proved to be simple and effective in treating these injuries.     

Reliability and validity of static knee strength measurements obtained with a chair-fixed dynamometer in subjects with hip or knee arthroplasty

OBJECTIVES: To evaluate the reliability (intertrial, interevaluator) and the concurrent validity of strength measurements obtained with a chair-fixed dynamometer and to recommend a clinical protocol that minimizes standard error of measurement (SEM). DESIGN: Within-session repeated measures of maximal static strength of knee flexors and extensors at 30 degrees and 60 degrees of flexion on the chair-fixed and Cybex dynamometers. SETTING: Ambulatory physiotherapy department of a rehabilitation hospital. PARTICIPANTS: Convenience sample of 50 subjects with total hip (n=25) or knee (n=25) arthroplasty. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Reliability was quantified by indices of dependability and corresponding SEMs estimated with the generalizability theory, whereas coefficients of correlation were used to assess the validity. RESULTS: Indices of dependability confirmed excellent intertrial (0.98-1.00) and a very good interevaluator (.92-.99) reliability for the strength measures obtained for different movements and positions. An average of 3 trials minimized the magnitude of the SEMs (>2 Nm for all measurements). When comparing the strength values obtained with the Cybex dynamometer to those measured with the chair-fixed dynamometer, strongest relations were attained when the tested knee was positioned at 60 degrees compared with 30 degrees for subjects with a total knee (.78-.92 vs .87-.93) or hip (.73-.85 vs .86-.91) arthroplasty. CONCLUSIONS: A clinical protocol averaging 3 trials with the knee positioned at 60 degrees after a familiarization period, both for knee flexors and extensors, performed by a trained therapist is recommended to minimize measurement errors on strength values measured with the chair-fixed dynamometer.     

Improving appointment-keeping by patients new to a hospital medical clinic with telephone or mailed reminders

A randomized trial of telephone and mailed reminders was conducted to assess their effect in reducing the rate of failure to keep appointments among patients new to a general medical clinic. Only 10% of the patients who received a telephone call and 12% of those who received a letter failed to keep their appointments compared with 20% of the control group (p less than 0.05). The most common reason given for failure to keep the appointment was lack of awareness of the appointment. Thus, telephone or mailed reminders can lower the rate of failure to keep appointments and result in greater satisfaction by patients and health care personnel.     

Subjective phenomena in drug trials.

Three types of problem arise from subjective phenomena in drug trials: problems of control, measurement, and analysis. Examples are given in order to illustrate these three aspects and to present some recent advances in clinical pharmacology. The author discusses the control of drug compliance, the validity of questionnaires, the subjectivity of the observer and that of the observations. Drug side-effects and the statistical analysis of qualitative data are presented in more detail.     

The estimation of heritability for twin data based on concordances of sex and disease

Heritability is an important measure in chronic disease epidemiology. Almost all developed methods of heritability estimation for dichotomous outcomes in twin data are based on concordance of monozygous (MZ) and dizygous (DZ) twins. However, most existing twin registries, which provide a unique and efficient opportunity to assess the putative genetic basis of diseases, do not have zygosity information. We developed a method that can be used to estimate the heritability for twin data with no information on zygosity. The only conditions on using this method are that the studied disease incidence is not strongly related to sex, and the distribution of zygosity is in accordance with Weinberg's rule. Using asthma twin data which has histological confirmed zygosity, we compared the results of our method with Holzinger's formula. The heritability of asthma was 24.88% (95% CI 21.98% - 27.78%) and 29.83% (95% CI 22.28% - 37.38%) estimated by our method and Holzinger's formula respectively. We conclude that our new method can be used in the estimation of heritability with large twin register data with no zygosity information available.