A systematic observation of moderate-to-vigorous physical activity levels in Australian natural blue space locations.

Research has shown that blue space (i.e. water-based environments) can be good for physical and mental health, with one possible reason being that people are physically active when visiting blue space environments. However, little is known about how active people are when visiting blue space. We used the System for Observing Physical Activity and Recreation in Natural Areas to systematically record whether people were active while visiting eight different blue space locations in Australia. We first calculated the proportion of people who were moderately or vigorously active at each location and then conducted a series of linear regression models to determine which demographic and environmental factors predicted higher activity levels. We identified that 44% of people visiting blue space locations were active. However, there were significant interactions between both age and gender, and type of blue space. Males (ß = -0.25, p = 0.018) and females (ß = -0.26, p ≤ 0.001) were less active at built-up riverfronts than coastal beaches. Females were also less active at inland beaches (ß = -0.15, p = 0.013) and watering holes (ß = -0.20, p = 0.011) compared with coastal beaches. Children (ß = 0.16, p = 0.006) and adolescents, however, were more active at inland beaches (ß = 0.32, p ≤ 0.001) than coastal beaches. These results are important to consider when making decisions around access to, and infrastructure within, blue space environments, as different blue space environments influence human behaviour differently for different people.

Participant Experiences With a Community-Based, "Older Adult" Walking Football Initiative in Australia: A Qualitative Exploration.

Despite the growing popularity of walking sports, little is known about who is attracted to them, and what skills, motivations, and experiences encourage ongoing participation. The aim of this study was to gain an in-depth understanding of the phenomenon of walking football in Australia. The authors first conducted semistructured interviews with 53 older adults (M = 62.37 years, 30.19% female) participating in walking football in Australia. Next, they conducted thematic analysis to develop themes that represented participant perspectives. Results indicated that walking football led to several physical benefits, but the social and mental benefits seemed to be more closely associated with continued participation. The slower pace of walking football created a valuable option to engage in physical activity among those with injuries or severe health issues, as well as older adults concerned about injuries. The slower pace also shifted the focus of walking football away from fitness and ability, and toward technique and skill development, and this focus, along with the mix in abilities, led to informal coaching and mentoring roles which were highly valued among older participants. Participant views about competition in walking football were diverse, with some expressing a mild concern. Understanding such diverse experiences of walking football helps to better understand how different aspects of the sport influence the perceived benefits and likelihood of continuing for different people. Using these findings to further develop walking sports in Australia could have large impacts on the health and well-being of older people.

Hospital factors associated with maternal and neonatal outcomes of deliveries to patients with a previous cesarean delivery: an ecological study.

BACKGROUND: Recommendations for deliveries of pregnant patients with a previous cesarean delivery and the type of hospitals deemed safe for these deliveries have evolved in recent years, although no studies have examined hospital factors and associated safety. We sought to evaluate maternal and neonatal outcomes among patients with a previous cesarean delivery by hospital tier and volume. METHODS: We carried out an ecological study of singleton live births delivered at term gestation to patients with a previous cesarean delivery in all Canadian hospitals (excluding Quebec), 2013-2019. We obtained data from the Discharge Abstract Database of the Canadian Institute for Health Information. The primary outcomes were severe maternal morbidity or mortality (SMMM), and serious neonatal morbidity or mortality (SNMM). We used regression modelling to examine hospital tier (tier 4 hospitals being those that provide the highest level of care) and volume; we also identified hospitals with high rates of SMMM and SNMM using within-tier comparisons and comparisons with the overall rate. RESULTS: We included 235 442 deliveries to patients with a previous cesarean delivery; SMMM and SNMM rates were 14.6 per 1000 deliveries and 4.6 per 1000 live births, respectively. Among patients with a parity of 1, SMMM rates were lower in tier 1 hospitals (adjusted incidence rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.52-0.89) and higher in tier 4 hospitals (adjusted IRR 1.41, 95% CI 1.05-1.91) than in tier 2 hospitals; SNMM rates did not differ by hospital tier. Rates of SNMM increased with increasing hospital volume (adjusted IRR 1.02, 95% CI 1.00-1.04) and increasing rates of vaginal birth after cesarean delivery (adjusted IRR 1.02, 95% CI 1.01-1.04). Most hospitals had relatively low SMMM and SNMM rates, although a few hospitals in each tier and volume category had significantly higher rates than others. INTERPRETATION: Adverse maternal and neonatal outcomes among patients with a previous cesarean delivery showed no clear pattern of decreasing SMMM and SNMM with increasing tiers of service and hospital volume. All hospitals, irrespective of tier or size, should continually review their rates of adverse maternal and neonatal outcomes.

Mode of delivery after a previous cesarean birth, and associated maternal and neonatal morbidity.

BACKGROUND: The mode of delivery for women with a previous cesarean delivery remains contentious. We conducted a study comparing maternal and infant outcomes after attempted vaginal birth after cesarean delivery versus elective repeat cesarean delivery. METHODS: We used data from the Discharge Abstract Database that includes all hospital deliveries in Canada (excluding Quebec). In our analysis, we included singleton deliveries to women between 37 and 43 weeks gestation who had a single prior cesarean delivery between April 2003 and March 2015. The primary outcomes were severe maternal morbidity and mortality, and serious neonatal morbidity and mortality. We used logistic regression to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Absolute rates of severe maternal morbidity and mortality were low but significantly higher after attempted vaginal birth after cesarean delivery compared with elective repeat cesarean delivery (10.7 v. 5.65 per 1000 deliveries, respectively; adjusted RR 1.96, 95% CI 1.76 to 2.19). Adjusted rate differences in severe maternal morbidity and mortality, and serious neonatal morbidity and mortality were small (5.42 and 7.09 per 1000 deliveries, respectively; number needed to treat 184 and 141, respectively). The association between vaginal birth after cesarean delivery, and serious neonatal morbidity and mortality showed a temporal worsening (adjusted RR 0.94, 95% CI 0.77 to 1.15 in 2003-2005; adjusted RR 2.07, 95% CI 1.83 to 2.35 in 2012-2014). INTERPRETATION: Although absolute rates of adverse outcomes are low, attempted vaginal birth after cesarean delivery continues to be associated with higher relative rates of severe morbidity and mortality in mothers and infants. Temporal worsening of infant outcomes after attempted vaginal birth after cesarean delivery highlights the need for greater care in selecting candidates, and more careful monitoring of labour and delivery.

The Value of an Informal Before-School Exercise Opportunity for Adolescent Girls Living in a Low-Socioeconomic Community.

BACKGROUND: Physical activity is beneficial to physical, social, and emotional well-being, and schools are required to provide opportunities to engage in physical activity. While physical education and school sport have been extensively researched, little is known about the value of informal, unstructured, exercise opportunities. METHODS: This study involved interviews with 19 adolescent girls who attended "extra" exercise opportunities provided by their school. The 3 opportunities were: (1) informal before-school exercise sessions at school, (2) before-school sport training, and (3) externally provided exercise sessions in a community setting during school hours. RESULTS: Students perceived all opportunities as valuable with benefits to confidence, social well-being, and emotional well-being. The informal exercise sessions held greater benefits to confidence as confidence transferred from the physical activity context into the academic classroom more so than for those participating in sport. Social benefits were greater for those exercising before school as this opportunity created new relationships with teachers and with students from other classes and year groups. CONCLUSIONS: The opportunity to engage in informal exercise with peers before school widened social networks, increased confidence, changed the overall school climate, and increased attendance.

Instruments for chorionic villus sampling for prenatal diagnosis.

BACKGROUND: Chorionic villus sampling (CVS) is the method of choice for obtaining fetal tissue for prenatal diagnosis before 15 weeks of pregnancy. CVS can be performed using either a transabdominal or transcervical approach. The type of instrument and technique used could have a significant impact on the outcome of the procedure. An ability to manoeuvre the instrument within the uterine cavity without puncturing the gestational sac, to see the tip of the instrument on ultrasound scanning and to minimise the number of instrument passes into the uterus are particularly important. OBJECTIVES: To compare the efficacy and safety of different instruments and techniques used to obtain chorionic tissue in early pregnancy by the transabdominal or transcervical route. Primary outcomes included failure to obtain an adequate sample (greater than 5 mg of chorionic villi), need for reinsertion of the instrument, pain, and miscarriage following the procedure. Secondary outcomes included mean weight of tissue obtained, successful culture, difficult instrument insertion, poor visualisation of instrument, vaginal bleeding following the procedure and cost per procedure. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2012). SELECTION CRITERIA: Randomised trials comparing different instruments (forceps, cannula, needle) or techniques for CVS using either transabdominal or transcervical approach. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility and trial quality. MAIN RESULTS: For transcervical CVS, forceps and cannulae were evaluated in five trials involving 472 women. When a cannula was used, operators failed to obtain an adequate sample (greater than 5 mg of chorionic villi) more often (average risk ratio (RR) 3.81; 95% confidence interval (CI) 1.52 to 9.56). There was no difference in the need for reinsertion of instruments (average RR 2.44; 95% CI 0.83 to 7.20). However, inserting a cannula was more painful (RR 1.93; 95% CI 1.11 to 3.37). There was no difference in spontaneous miscarriage when the use of a cannula was compared with biopsy forceps (RR 1.00; 95% CI 0.14 to 6.96). One study reported the cost of the procedures and found CVS with a cannula to be more expensive (mean difference (MD) $183.7; 95% CI 152.62 to 214.78).When different types of cannulae for transcervical CVS were compared, a Portex cannula was more likely to result in an inadequate sample (RR 2.23; 95% CI 1.25 to 3.98) compared with the silver cannula and to result in a difficult (RR 3.26; 95% CI 1.38 to 7.67) or painful (RR 5.81; 95% CI 1.41 to 23.88) procedure when compared with the aluminium cannula.For transabdominal CVS, two trials comparing different needle techniques were included involving 285 women. One study using an ex vivo system of term placentae was excluded. The included trials compared different continuous negative pressure aspiration techniques with a discontinuous negative pressure system created by a syringe attached to a 20 gauge needle. The studies produced discrepant results. One study found there was no significant difference between groups in the mean weight of chorionic villi obtained (MD 0.40; 95% CI -2.25 to 3.05) or in failure to obtain an adequate sample (more than 5 mg of chorionic villi) on the first attempt (RR 1.02; 95% CI 0.54 to 1.93), whereas the other study found both of these outcomes to be significantly less favourable with the standard discontinuous technique using a syringe (mean weight of chorionic villi obtained: MD -14.80; 95% CI -21.71 to -7.89; failure to obtain an adequate sample on the first attempt: RR 2.73; 95% CI 1.08 to 6.92). There was no difference in rate of miscarriage following the procedure in either study (RR 7.15; 95% CI 0.37 to 136.50; RR 2.93; 95% CI 0.12 to 70.00). Perceived pain by the patient was similar between groups (MD 0.00; 95% CI -0.04 to 0.04) as was success of culture (no failed cases). AUTHORS' CONCLUSIONS: For transcervical CVS, although there is some evidence to support the use of small forceps instead of cannulae, the evidence is not strong enough to support change in practice for clinicians who have become familiar with a particular technique. For transabdominal CVS, based on current evidence, there is no difference in clinically important outcomes with the use of a continuous compared with a discontinuous negative pressure needle aspiration system.

Mouth Rinsing Cabohydrates Serially Does Not Improve Repeated Sprint Time.

Sensing carbohydrates via the oral cavity benefits performance outcomes during brief high intensity bouts of exercise. However, the extent to which carbohydrates need to be present in the oral cavity to influence sprint performance is less understood. The purpose of this study was to determine if serial increases in carbohydrate rinse time across sprint sets attenuates increases in sprint time compared to no serial increases in carbohydrate rinse time across sprint sets. Fifteen sprint trained participants completed three repeated anaerobic sprint tests (RAST), 3 sets of 6 x 35-m sprints, under two different carbohydrate mouth rinsing (CMR) conditions; (1) rinsing for only 5 seconds (s), and (2) rinsing for 5 s, 10 s and 15 s (serial rinse). Prior to a RAST, participants provided perceived recovery status (PRS) and perceived feeling of arousal (FAS). Upon completion of each individual sprint, participants gave a rating of perceived exertion (RPE). A lactate sample was taken upon completion of each individual sprint set and after all 3 RASTs a session rating of perceived exertion (S-RPE) was measured. There were no significant differences in peak (p = 0.18) and average sprint time (p = 0.41). There were no significant differences in perceptual measures: RPE, PRS, FAS, S-RPE or for blood lactate concentration between CMR conditions. Overall, serial rinsing resulted in changes that were most likely trivial, but showed a 50% chance in perceiving a sprint session as less difficult. Rinsing carbohydrates in a serial manner between repeated sprint sets produces trivial changes of sprint speed and perceptual measures from sprint performance.

Society of obstetricians and gynaecologists of Canada junior member committee survey: future career plans of Canadian obstetrics and gynaecology residents.

OBJECTIVE: Although the SOGC Strategic Directions 2006-2011 includes a commitment to the development of a human resource strategy for obstetrical and gynaecological care, little is known about the career plans of Canadian obstetrics and gynaecology residents. If we are to determine the needs of our profession, we must be aware of the expected practice patterns of future women's health care providers. The primary objective of this study was to evaluate the future career plans of Canadian obstetrics and gynaecology residents. METHODS: The SOGC Junior Member Committee administered two career surveys to Canadian obstetrics and gynaecology residents. The first was directly distributed to all Canadian residents and collected by local representatives of the SOGC Junior Member Committee in November 2002. The second was electronically administered from November 2005 to January 2006. The data collected from the surveys were collated and analyzed using statistical analysis software. RESULTS: The first survey, in 2002, was completed by 236 obstetrics and gynaecology residents (68% response rate) and the second, in 2006, by 246 (65% response rate). In both surveys, respondents were evenly distributed over all five years of residency training and all residency training programs. In 2002, 63 residents (30%) were considering additional postgraduate fellowship training following completion of residency compared with 130 residents (53%) in 2006 (P < 0.001). In both surveys, senior residents (postgraduate years IV and V) were significantly less likely to consider further postgraduate training than residents in their first three years (2002: 17% vs. 38%; 2006: 42% vs. 58%). Of total respondents to the 2002 and 2006 surveys, 87% planned to practice obstetrics upon graduation. The 2006 survey also found that the majority of residents desired to work in call groups of 6 to 10 physicians, work three to five on-call shifts per month, and work a 40- to 60-hour week; 44% of residents planned work as locums after graduation. CONCLUSION: Recognition of the planned practice patterns of our current residents may assist in the development of an appropriate human resource strategy for future obstetrical and gynaecological care in Canada.

First-Year University Students Who Self-Select into Health Studies Have More Desirable Health Measures and Behaviors at Baseline but Experience Similar Changes Compared to Non-Self-Selected Students.

Studies demonstrate that first-year university students are at high risk for weight gain. These reports typically rely on self-selected participants. The purpose of this study was to explore if students who chose to participate in a health-based research study had more desirable health measures and behaviors than students who completed health assessments as part of a first-year seminar course. Health measures included blood pressure (BP), body mass index (BMI), and percent body fat. Health behaviors included dietary patterns (Starting the Conversation questionnaire) and alcohol use (Alcohol Use Disorders Identification Test-Consumption). A total of 191 (77% female) participants completed testing in the self-selected "Health Study" group, whereas 73 of the 91 students (80%, 55% female) enrolled in the "Seminar" allowed their data to be used for research purposes. Baseline measures favored Health Study participants, including but not limited to fewer participants with undesirable BMI (≥25.0 kg/m²; males and females) and a smaller percentage of participants with undesirable BP (systolic ≥120 mmHg and/or diastolic ≥80 mmHg; females only). Differences in dietary behaviors at baseline were inconsistent, but Seminar students engaged in more problematic alcohol-use behaviors. While both groups experienced undesirable changes in health measures over time, the degree of change did not differ between groups. Changes in health behaviors over time typically resulted in undesirable changes in the Seminar group, but the magnitude of change over time did not differ between groups. Thus, results from first-year university students who self-select into health studies likely underestimate the seriousness of undesirable health measures and behaviors but may accurately reflect the degree of change over time.

Maternal morbidity associated with early-onset and late-onset preeclampsia.

OBJECTIVE: To examine temporal trends in early-onset compared with late-onset preeclampsia and associated severe maternal morbidity. METHODS: The study included all singleton deliveries in Washington State between 2000 and 2008 (N=670,120). Preeclampsia onset was determined using hospital records linked to birth certificates. Severe maternal morbidity was defined as any potentially life-threatening condition. Logistic regression was used to obtain adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: The preeclampsia rate was 3.0 per 100 singleton births, and increased slightly from 2.9 to 3.1 between 2000 and 2008. Rates of early-onset and late-onset disease were 0.3% and 2.7%, respectively. The temporal increase was significant only for early-onset disease (4.5%/year; 95% CI 2.3-5.8%) after adjustment for changes in maternal characteristics. Maternal death rates were higher among women with early-onset (42.1/100,000 deliveries) and late-onset preeclampsia (11.2/100,000) compared with women without preeclampsia (4.2/100,000). The rate of severe maternal morbidity (excluding obstetric trauma) was 12.2 per 100 deliveries in the early-onset group (aOR 3.7, 95% CI 3.2-4.3), 5.5 per 100 deliveries in the late-onset group (aOR 1.7, 95% CI 1.6-1.9), and approximately 3 per 100 in women without preeclampsia. Early-onset preeclampsia conferred a substantially higher risk of cardiovascular, respiratory, central nervous system, renal, hepatic, and other morbidity. However, rates of obstetric trauma were significantly lower among women with preeclampsia. CONCLUSION: Women with early-onset and late-onset preeclampsia have significantly higher rates of specific maternal morbidity compared with women without early-onset and late-onset disease. LEVEL OF EVIDENCE: : II.

A case of alloimmune thrombocytopenia, hemorrhagic anemia-induced fetal hydrops, maternal mirror syndrome, and human chorionic gonadotropin-induced thyrotoxicosis.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin-induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

Enterobius vermicularis infection of the fallopian tube in an infertile female.

Enterobius vermicularis (EV) is the most common nematode to infect humans. It inhabits the intestinal lumen, but rare, ectopic infections have been documented. The female genital tract is the most common ectopic site. We present a unique case of an EV infection of the fallopian tube resulting in inflammation, tubal obstruction, and infertility. A 30-year-old woman presented with infertility. Investigations included a laparoscopy with hydrotubation using methylene blue dye. This showed a left fallopian tube obstruction and extensive pelvic adhesions. A left salpingectomy was performed. Microscopic examination of the fallopian tube revealed numerous calcified and non-calcified ova associated with granulomatous reaction. The microscopic features were compatible with EV infection. Ectopic EV infections of the female genital tract result when the gravid female worm migrates from the perianal area to the vagina and ascends through the uterus and fallopian tubes to the peritoneal cavity. Microscopic examination of these ectopic sites can reveal adult worms or ova with granulomata formation, eosinophilic infiltrate, chronic inflammatory reaction, and fibrosis. The ova have a characteristic asymmetric oval configuration with flattening on one side. We postulate that our patient's salpingitis due to EV with accompanying fibrosis is a cause of her infertility.

Evaluation of a model to predict poor survival in patients undergoing elective TIPS procedures.

PURPOSE: To validate a previously published model to predict the probability of patient death within 3 months after an elective transjugular intrahepatic portosystemic shunt (TIPS) procedure. The model is implemented with use of a nomogram or a formula. MATERIALS AND METHODS: Patients who underwent an elective TIPS procedure between May 1, 1999, and May 1, 2001, were selected. Patients who underwent emergency TIPS creation and patients with serum creatinine levels greater than 3.0 mg/dL were excluded. A total of 72 patients met the inclusion criteria. The patients were divided into two groups: group A (ethanol-induced cirrhosis; n = 23) and group B (non-ethanol-induced cirrhosis; n = 49). The model was applied and the predicted probability of death was compared to actual patient survival. A high risk score (R > or = 1.8) is associated with a high risk of death within 3 months after TIPS creation. Survival curves were estimated with use of Kaplan-Meier product limit estimates and were compared with use of the log-rank test. The model's accuracy was evaluated with use of the c-statistic. P values lower than.05 indicated statistical significance. RESULTS: The technical success rate was 98.7%. The 3-month survival rate for the whole group was 79.7%. The predicted mortality rate was higher than the observed mortality rate. The c-statistic was 0.65 for the formula and 0.66 for the nomogram. Patients with a risk score of at least 1.8 had a 3-month survival rate of 54.6% and patients with a risk score lower than 1.8 had a 3-month survival rate of 84.9% (P =.037). CONCLUSION: These results confirm that, after an elective TIPS procedure, patients with risk scores of at least 1.8 have a significantly lower 3-month survival rate than patients with risk scores lower than 1.8.

Survival after elective transjugular intrahepatic portosystemic shunt creation: prediction with model for end-stage liver disease score.

PURPOSE: To evaluate the ability of a model of end-stage liver disease (MELD) score to predict survival in a diverse group of patients who underwent elective transjugular intrahepatic portosystemic shunt (TIPS) creation in two tertiary care institutions. MATERIALS AND METHODS: Patients who underwent elective TIPS creation in two institutions between May 1, 1999, and June 1, 2002, were selected. Patients who underwent emergency TIPS creation were excluded. One hundred sixty-six patients met the inclusion criteria. The MELD score was computed and compared with the survival rate. Survival curves were estimated with Kaplan-Meier product limit estimates and were compared with the log-rank test. Accuracy of the model was evaluated with the c statistic. RESULTS: The survival rate for all patients was 88.4% at 30 days, 78.1% at 3 months, and 71.8% at 6 months. Significantly lower survival rates were found in patients with MELD scores of 18 or more in comparison to those with MELD scores of 17 or less (P =.001). The c statistic for prediction of 3-month survival on the basis of the MELD score was 0.76. The early (30-day) death rate for this series was 11.4%. There was a significant difference in the 30-day mortality rate between patients with MELD scores of 17 or less and those with scores of 18 or more (P =.001). Patients who underwent TIPS creation for the management of refractory ascites had a significantly lower survival rate in comparison to that for the management of variceal bleeding (P =.001). CONCLUSION: Results confirm that after elective TIPS creation, patients with a MELD score of 18 or more have a significantly lower 3-month survival rate than do those with a MELD score of 17 or less.

The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis.

The disulfide structure of the CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto protein was determined by a combination of enzymatic and chemical fragmentation, followed by chromatographic separation of the fragments, and characterization by mass spectrometry and N-terminal sequencing. These studies showed that Cys115 forms a disulfide bond with Cys133, Cys128 with Cys149, and Cys131 with Cys140. Protein database searching and molecular modeling revealed that the pattern of disulfide linkages in the CFC domain of Cripto is the same as that in PARS intercerebralis major Peptide C (PMP-C), a serine protease inhibitor, and that the EGF-CFC domains of Cripto are predicted to be structurally homologous to the EGF-VWFC domains of the C-terminal extracellular portions of Jagged 1 and Jagged 2. Biochemical studies of the interactions of ALK4 with the CFC domain of Cripto by fluorescence-activated cell sorter analysis indicate that the CFC domain binds to ALK4 independent of the EGF domain. A molecular model of the CFC domain of Cripto was constructed based on the nuclear magnetic resonance structure of PMP-C. This model reveals a hydrophobic patch in the domain opposite to the presumed ALK4 binding site. This hydrophobic patch may be functionally important for the formation of intra or intermolecular complexes.

Expression, purification, and characterization of rat interferon-beta, and preparation of an N-terminally PEGylated form with improved pharmacokinetic parameters.

To identify potential new clinical uses and routes of administration for human interferon-beta-1a (IFN-beta-1a), we have developed an expression and purification procedure for the preparation of highly purified rat interferon-beta (IFN-beta) suitable for testing in rat models of human disease. An expression vector containing the rat IFN-beta signal sequence and structural gene was constructed and transfected into Chinese hamster ovary (CHO) cells. The protein was purified from CHO cell conditioned medium and purified to > 99.5% purity using standard chromatographic techniques. Analytical characterization indicated that the protein was a heavily glycosylated monomeric protein, with two of the four predicted N-glycosylation sites occupied. Analysis of the attached oligosaccharides showed them to be a complex mixture of bi-antennary, tri-antennary, and tetra-antennary structures with a predominance of sialylated tri-antennary and tetra-antennary structures. Peptide mapping, N-terminal sequencing, and mass spectrometry confirmed the identity and integrity of the purified protein. The purified protein had a specific activity of 2.1x10(8)U/mg when assayed on rat RATEC cells, which is similar in magnitude to the potencies observed for murine IFN-beta and human IFN-beta-1a assayed on murine and human cells, respectively. We also prepared an N-terminally PEGylated form of rat IFN-beta in which a 20 kDa methoxy polyethylene glycol (PEG)-propionaldehyde was attached to the N-terminal alpha-amino group of Ile-1. The PEGylated protein, which retained essentially full in vitro antiviral activity, had improved pharmacokinetic parameters in rats as compared to the unmodified protein. Both the unmodified and PEGylated forms of rat IFN-beta will be useful for testing in rat models of human disease.