Search

There is currently no published information on the full range of morbid conditions affecting mothers and newborns in Australia. Hospital morbidity data collections are a possible source of this information, but have not been widely utilised due to concerns about data quality.To assess the accuracy and reliability of perinatal morbidity reporting to the New South Wales Inpatient Statistics Collection (NSW ISC).A sample of 1000 records relating to 500 mothers and 500 newborns were randomly selected from the NSW ISC for the financial year 1999–2000 and compared with information obtained from medical records. Sensitivities and specificities were calculated for conditions of clinical relevance.There was a wide range of sensitivities among the 41 conditions selected, indicating a variable level of under-enumeration. Only 17 (41%) had a sensitivity of 80% or more. Sensitivities were more than 95% for gestational diabetes, prolonged pregnancy, perineal laceration, single live birth, low birth weight, and intracranial haemorrhage. However, numbers are small and confidence intervals wide for some of these conditions. Specificities were generally high. Neonatal conditions tended to be more accurately reported than maternal conditions. The pattern of results was similar to that reported for state perinatal data collections.While hospital administrative data are readily available, data quality is a valid concern. However, if the data are viewed critically and information on accuracy is available, they can be a useful resource for monitoring the health of mothers and babies. [ABSTRACT FROM AUTHOR]

Objectives: To determine antenatal factors associated with the need for ventilatory support in babies born between 30 and 36 weeks gestational age and use this information to help referring obstetricians decide which mothers need antenatal transfer.Methods: Babies born at Royal Prince Alfred Hospital at 30-36 weeks' gestation inclusive between January 1992 to December 1999 were identified in the obstetric and neonatal databases. Information for a wide range of antenatal factors and respiratory outcomes was extracted. Babies with major congenital anomalies were excluded. Statistical analysis using spss for Windows was then undertaken.Results: Data were available for 3102 babies. On univariate analysis, seven factors were significant. Lower gestational age, absence of labour, Caesarean section, antepartum haemorrhage, breech presentation and hypertensive disease of pregnancy were associated with increased risk, while threatened premature labour was protective. On logistic regression analysis, gestational age and absence of labour dominated the model. Other significant factors in the model had a relatively minor impact.Conclusions: The risk of needing ventilatory support according to antenatal risk factors is described for infants born between 30 and 36 weeks. Gestational age and absence of labour were found to be the major determinants of risk. Delivery without labour increased the risk by the equivalent of about 2 weeks of gestation. For example, to avoid a risk > 20%, the cut off is 33 weeks for mothers who labour, but is increased to 35 weeks when there is no labour. Our results should be interpreted with caution, as the patients in a tertiary obstetric unit may not be typical of the wider community. [ABSTRACT FROM AUTHOR]

Background: Rates of maternal and perinatal mortality remain high in developing countries despite the existence of effective interventions. Efforts to strengthen evidence-based approaches to improve health in these settings are partly hindered by restricted access to the best available evidence, limited training in evidence-based practice and concerns about the relevance of existing evidence. South East Asia--Optimising Reproductive and Child Health in Developing Countries (SEA-ORCHID) was a five-year project that aimed to determine whether a multifaceted intervention designed to strengthen the capacity for research synthesis, evidence-based care and knowledge implementation improved clinical practice and led to better health outcomes for mothers and babies. This paper describes the development and design of the SEA-ORCHID intervention plan using a logical framework approach.Methods: SEA-ORCHID used a before-and-after design to evaluate the impact of a multifaceted tailored intervention at nine sites across Thailand, Malaysia, Philippines and Indonesia, supported by three centres in Australia. We used a logical framework approach to systematically prepare and summarise the project plan in a clear and logical way. The development and design of the SEA-ORCHID project was based around the three components of a logical framework (problem analysis, project plan and evaluation strategy).Results: The SEA-ORCHID logical framework defined the project's goal and purpose (To improve the health of mothers and babies in South East Asia and To improve clinical practice in reproductive health in South East Asia), and outlined a series of project objectives and activities designed to achieve these. The logical framework also established outcome and process measures appropriate to each level of the project plan, and guided project work in each of the participating countries and hospitals.Conclusions: Development of a logical framework in the SEA-ORCHID project enabled a reasoned, logical approach to the project design that ensured the project activities would achieve the desired outcomes and that the evaluation plan would assess both the process and outcome of the project. The logical framework was also valuable over the course of the project to facilitate communication, assess progress and build a shared understanding of the project activities, purpose and goal. [ABSTRACT FROM AUTHOR]

Objective: To identify prenatal risk factors for chronic lung disease (CLD) at 36 weeks postmenstrual age in very preterm infants.Population: Data were collected prospectively as part of the ongoing audit of the Australian and New Zealand Neonatal Network (ANZNN) of all infants born at less than 32 weeks gestation admitted to all tertiary neonatal intensive care units in Australia and New Zealand.Methods: Prenatal factors up to 1 minute of age were examined in the subset of infants born at gestational ages 22-31 weeks during 1998-2001, and who survived to 36 weeks postmenstrual age (n = 11 453). Factors that were significantly associated with CLD at 36 weeks were entered into a multivariate logistic regression model.Results: After adjustment, low gestational age was the dominant risk factor, with an approximate doubling of the odds with each week of decreasing gestational age from 31 to less than 25 weeks (trend p<0.0001). Birth weight for gestational age also had a dose-response effect: the lower the birth weight for gestational age, the greater the risk, with infants below the third centile having 5.67 times greater odds of CLD than those between the 25th and 75th centile (trend p<0.0001). There was also a significantly increased risk for male infants (odds ratio 1.51 (95% confidence interval 1.36 to 1.68), p<0.0001).Conclusions: These population based data show that the prenatal factors low gestational age, low birth weight for gestational age, and male sex significantly predict the development of chronic respiratory insufficiency in very preterm infants and may assist clinical decision about delivery. [ABSTRACT FROM AUTHOR]

Compared with term infants, little information is available about the usefulness of the umbilical artery pH in relation to outcome in extremely preterm infants. This prospective study evaluates the relation between umbilical artery pH (UapH), Apgar scores, perinatal events, and outcome in infants born at less than 32 weeks' gestation. Six hundred and twenty three infants of < 32 weeks' gestation were studied. The median UapH was 7.25, with a range of 6.78-7.49. A low UapH was significantly associated with male sex, hyaline membrane disease, grade 3 or 4 intraventricular haemorrhage, and neonatal death. It was also associated with lower birth weight and lower birthweight centile. The relations between the UapH and outcomes of neonatal death, cerebral palsy, and developmental quotient at 1 year, and other perinatal risk factors were then examined using multiple logistic regression. After adjusting for other risk factors, UapH was not significantly associated with any outcome. In contrast, a low one minute Apgar (< 4) remained a significant risk factor, with odds ratios of 2.7 (95% confidence interval (CI) 1.5 to 5.2) for neonatal death and 3.8 (95% CI 1.4 to 10.4) for cerebral palsy. [ABSTRACT FROM AUTHOR]

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to identify, discuss and develop recommendations for optimal scientific and technical approaches for conducting in vitro assays, to assess potential toxicity within and across tobacco and various next generation nicotine and tobacco products (NGPs), including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS). The third workshop (24-26 February 2020) summarised the key challenges and made recommendations concerning appropriate methods of test article generation and cell exposure from combustible cigarettes, HTPs and ENDS. Expert speakers provided their research, perspectives and recommendations for the three basic types of tobacco-related test articles: i) pad-collected material (PCM); ii) gas vapour phase (GVP); and iii) whole smoke/aerosol. These three types of samples can be tested individually, or the PCM and GVP can be combined. Whole smoke/aerosol can be bubbled through media or applied directly to cells at the air-liquid interface. Summaries of the speaker presentations and the recommendations developed by the workgroup are presented. Following discussion, the workshop concluded the following: that there needs to be greater standardisation in aerosol generation and collection processes; that methods for testing the NGPs need to be developed and/or optimised, since simply mirroring cigarette smoke testing approaches may be insufficient; that understanding and quantitating the applied dose is fundamental to the interpretation of data and conclusions from each study; and that whole smoke/aerosol approaches must be contextualised with regard to key information, including appropriate experimental controls, environmental conditioning, analytical monitoring, verification and performance criteria.

Electronic nicotine delivery systems (ENDS) are being developed as potentially reduced-risk alternatives to the continued use of combustible tobacco products. Because of the widespread uptake of ENDS-in particular, e-cigarettes-the biological effects, including the toxic potential, of their aerosols are under investigation. Preclinically, collection of such aerosols is a prerequisite for testing in submerged cell culture-based in vitro assays; however, despite the growth in this research area, there is no apparent standardized collection method for this application. To this end, through an Institute for in vitro Sciences, Inc. workshop initiative, we surveyed the biomedical literature catalogued in PubMed® to map the types of methods hitherto used and reported publicly. From the 47 relevant publications retrieved, we identified seven distinct collection methods. Bubble-through (with aqueous solvents) and Cambridge filter pad (CFP) (with polar solvents) collection were the most frequently cited methods (57% and 18%, respectively), while the five others (CFP + bubble-through; condensation; cotton filters; settle-upon; settle-upon + dry) were cited less often (2-10%). Critically, the collected aerosol fractions were generally found to be only minimally characterized chemically, if at all. Furthermore, there was large heterogeneity among other experimental parameters (e.g., vaping regimen). Consequently, we recommend that more comprehensive research be conducted to identify the method(s) that produce the fraction(s) most representative of the native aerosol. We also endorse standardization of the aerosol generation process. These should be regarded as opportunities for increasing the value of in vitro assessments in relation to predicting effects on human health., (© 2020 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

In vitro genetic toxicology assays are used to assess the genotoxic potential of chemicals or mixtures. They measure chromosome damage (e.g., micronucleus [MN] formation) or gene mutation, and different combinations of data generated from such assays are evaluated in concert in order to identify genotoxic hazards. Mode-of-action (MoA) information is also fundamental to understanding any apparent genotoxic response. In view of the importance of these types of data for full characterization of genotoxic potential, we leveraged relevant endpoints already established in the human TK6 cell line to develop a single integrated assay that measures MN formation, gene mutation (at the thymidine kinase locus), and MoA (DNA damage response biomarkers). Several prototypical direct-acting genotoxins (methyl methanesulfonate, mitomycin C, and 4-nitroquinoline 1-oxide), pro-genotoxins (benzo[a]pyrene and cyclophosphamide monohydrate), and one non-DNA reactive genotoxin (vinblastine sulfate) were assessed in the approach and found to elicit genotoxic profiles that were generally consistent with their MoA. In contrast, the non-genotoxic agents D-mannitol and (2-chloroethyl) trimethyl-ammonium chloride induced negligible effects on all endpoints up to a top concentration of 10 mM. Sodium diclofenac, presumed to be non-genotoxic, provoked an induction in the phosphoserine 10 -H3-positive cell population within a small window of concentrations (0.157-0.314 mM), as well as increases in γH2AX, nuclear p53, and MN at higher concentrations, although it had no effect on the mutation frequency endpoint. G 2 M cell cycle arrest was also largely observed in cells that exhibited genotoxicity in the in vitro MN assay. The TK6 cell-based integrated assay represents an in vitro approach that permits comprehensive genotoxicity analysis in a human-relevant test system. Moreover, its vis-à-vis nature may facilitate further comprehension of the range of effects that can manifest in human cells in response to DNA-damaging agents., Competing Interests: Declaration of Competing Interest All authors are employees of Philip Morris International., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nicotine's genotoxic potential has been extensively studied in vitro. While the results of mammalian cell-based studies have inferred that it can potentially damage chromosomes, in general and with few exceptions, adverse DNA effects have been observed primarily at supraphysiological concentrations in nonregulatory assays that provide little information on its mode-of-action (MoA). In this study, a modern-day regulatory genotoxicity assessment was conducted using a flow cytometry-based in vitro micronucleus (MN) assay, Good Laboratory Practice study conditions, Chinese hamster ovary cells of known provenance, and acceptance/evaluation criteria from the current OECD Test Guideline 487. Nicotine concentrations up to 3.95 mM had no effect on background levels of DNA damage; however, concentrations above the point-of-departure range of 3.94-4.54 mM induced increases in MN and hypodiploid nuclei, indicating a possible aneugenicity hazard. Follow-up experiments designed to elucidate nicotine's MoA revealed cellular vacuolization, accompanying distortions in microtubules, inhibition of tubulin polymerization, centromere-positive DNA, and multinucleate cells at MN-inducing concentrations. Vacuoles likely originated from acidic cellular compartments (e.g., lysosomes). Remarkably, genotoxicity was suppressed by chemicals that raised the luminal pH of these organelles. Other endpoints (e.g., changes in phosphorylated histones) measured in the study cast doubt on the biological relevance of this apparent genotoxicity. In addition, three major nicotine metabolites, including cotinine, had no MN effects but nornicotine induced a nicotine-like profile. It is possible that nicotine's lysosomotropic properties drive the genotoxicity observed in vitro; however, the potency and mechanistic insights revealed here indicate that it is likely of minimal physiological relevance for nicotine consumers. Environ. Mol. Mutagen. 2019. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society., (© 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.)

Cytotoxicity assays are used to quantify the cytotoxic potential of chemicals. The neutral red uptake (NRU) assay is one of these assays and is routinely used in the pharmaceutical, cosmetic, and tobacco industries. In the context of e-cigarette development, an NRU assay-based screen was implemented to evaluate the cytotoxic potential of e-liquids. E-liquids induced a biphasic response in the BALB/c 3T3-based assay. The NRU initially increased in a concentration-dependent manner before decreasing following treatment with higher concentrations until NRU was abolished. Experiments were performed to characterize the mechanism underlying this biphasic signal. Nicotine alone was found to induce the same biphasic effects, while inducing concentration-dependent decreases in relative cell counts (RCC). Imaging and flow cytometry data revealed that the increases in NRU likely resulted from nicotine-induced vacuolization via a lysosomotropic mechanism. In support of this, two lysosomotropic agents, chloroquine and lapatinib, induced similar profiles. Nicotine's effects were also translatable, as brain-, lung-, bone marrow-, and smooth muscle-derived mammalian cells responded with the biphasic NRU signal. However, like RCC, three other cytotoxicity endpoints, resazurin, adenosine triphosphate, and water soluble tetrazolium salt (WST)-8, were not subject to these effects. The WST-8 assay is proposed as an alternative to screen the cytotoxic potential of e-liquids., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigated the relationship between vertical and horizontal measures in bilateral and unilateral countermovement jump, drop jump and squat jump (SJ), and sprinting speed and muscle architecture of both the vastus lateralis and gastrocnemius. Subjects (n = 17) completed a 30-m sprint test, muscle stiffness test; ultrasound measures, and a jump testing session. Measures of horizontal peak and mean force, in both bilateral and unilateral jumps, tended to have greater relationships to sprint speeds (R = 0.132-0.576) than peak and mean force in the vertical plane (R = 0.008-0.504). Vertical velocity variables also showed some large and very large correlations to sprint speed (R = 0.062-0.635). Unilateral measures of velocity tended to have larger correlations to sprint performance than their bilateral counterparts across all jump types and peak and mean velocity in SJ showed large and very large correlations to sprint speed (bilateral R = 0.227-0.635; unilateral 0.393-0.574). Few large correlations were shown between muscle stiffness measures of muscle architecture and kinetic and kinematic variables in either vertical or horizontal jumps. The present findings suggest that sport scientists and strength and conditioning practitioners concerned with the prognostic value of kinetic variables to functional movements such as sprint speed should also use horizontal jumps in addition to vertical jumps in testing and training.

The purpose of this study was to investigate the chronic effect of a contrast training program designed to elicit an acute short term enhancement (STE) effect during training. A matched pairs training study design was implemented with a contrast (STE affected) and complex (control) training group completing a seven week training intervention. Twenty subjects participated. The contrast training group completed training based on a preloading protocol that had previously been shown to induce an acute STE effect within the subject population. The control group completed the same volume and type of training in a complex training format. Changes in squat 4RM strength and kinetic and kinematic performance in vertical and horizontal countermovement jump (CMJ) and drop jump (DJ) were measured via a Force Plate. Differences between the experimental and control group in change of mean strength (effect size 0.03 ± 0.33), vertical DJ (effect size: contact time -0.22 ± 0.52; peak force 0.20 ± 0.30; mean force 0.30 ± 0.74) and horizontal DJ (effect size: contact time -0.47 ± 0.73; peak force 0.03 ± 0.36; mean force 0.13 ± 0.56) were not meaningful. However, differences in mean change of vertical and horizontal CMJ measures of force (effect size range 0.40 - 0.46 ± 0.37 - 0.63), vertical CMJ peak velocity (effect size 0.84 ±0.66) and mean velocity (0.62 ± 0.88) were meaningful. These findings demonstrate that eliciting an acute STE response in dynamic training movements through contrast training can produce a chronic improvement in dynamic movements as a training effect.

Numerous studies have highlighted differences between playing levels and positions in rugby union; however, few studies have investigated longitudinal progressions of body composition and physical performance. Between-player differences and within-player changes in body composition, strength, power, speed, and repeated sprint ability, from 1,161 New Zealand rugby union players from 2004 to 2007, were estimated using a mixed modeling procedure. Props had the highest mass, percent body fat, strength, and slowest speed times compared with the other positions, whereas outside backs had the fastest speed time and lowest percent body fat. For most measures, there were small-to-moderate differences (range, 1.1-14%) between players selected and not selected for provincial teams and small-to-large differences (range, 1.8-15%) between provincial and Super Rugby (professional) players. The faster 20-m sprint times in international compared with Super Rugby players was small in magnitude for both the forwards (1.9%) and backs (2.2%). The average annual improvements were small to moderate for strength (range, 2.1-15%) and small for repeated sprint ability within the lower playing levels (~1.5%). Small increases occurred in lower body strength (~7.0%) as players moved from Super Rugby to provincial competition. Small decreases in sprint time (~1.6%) and small increases in strength (~6.3%) occurred as players moved from Super Rugby to midyear international competition. The differences between levels in performance provide level-specific characteristics from Super Rugby and below, but international players may be selected because of greater skill and experience. Changes in physical performance between competitions may be a result of reduced training loads because of regular high-intensity matches and greater travel involved in the Super Rugby competition.

Fluoroquinolone (FQ) antibiotics are bacteriocidal through inhibition of the bacterial gyrase and at sufficient concentrations in vitro, they can inhibit the homologous eukaryotic topoisomerase (TOPO) II enzyme. FQ exert a variety of genotoxic effects in mammalian systems through mechanisms not yet established, but which are postulated to involve inhibition of TOPO II enzymes. To assess the relationship of inhibition of cell nuclear TOPO II to cytotoxicity and reported genotoxicity, two FQ, clinafloxacin (CLFX) and lomefloxacin (LOFX), having available genotoxicity data showing substantial differences with CLFX being more potent than LOFX, were selected for study. The relative inhibitory activities of these FQ on nuclear TOPO IIα in cultured Chinese hamster lung fibroblasts (V79 cells) over dose ranges and at equimolar concentrations were assessed by measuring nuclear stabilized cleavage complexes of TOPO IIα-DNA. Cytotoxicity was measured by relative cell counts. Both FQ inhibited V79 cell nuclear TOPO IIα. The lowest-observed-adverse-effect levels for TOPO IIα inhibition were 55 μM for CLFX, and 516 μM for LOFX. The no-observed-adverse-effect-levels were 41 μM for CLFX, and 258 μM for LOFX. At equimolar concentrations (175 μM), CLFX was more potent than LOFX. Likewise, CLFX was more cytotoxic than LOFX. Thus, the two FQ, inhibited TOPO IIα in intact V79 cells, differed in their potencies and exhibited no-observed-adverse-effect levels. These findings are in concordance with published genotoxicity data and observed cytotoxicity., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The aims of the study were to determine if a supervised off-season conditioning program enhanced gains in physical characteristics compared with the same program performed in an unsupervised manner and to establish the persistence of the physical changes after a 6-month unsupervised competition period. Forty-four provincial representative adolescent rugby union players (age, mean ± SD, 15.3 ± 1.3 years) participated in a 15-week off-season conditioning program either under supervision from an experienced strength and conditioning coach or unsupervised. Measures of body composition, strength, vertical jump, speed, and anaerobic and aerobic running performance were taken, before, immediately after, and 6 months after the conditioning. Post conditioning program the supervised group had greater improvements in all strength measures than the unsupervised group, with small, moderate and large differences between the groups\x{2019} changes for chin-ups (9.1%; ± 11.6%), bench-press (16.9%; ± 11.7%) and box-squat (50.4%; ± 20.9%) estimated 1RM respectively. Both groups showed trivial increases in mass; however increases in fat free mass were small and trivial for supervised and unsupervised players respectively. Strength declined in the supervised group while the unsupervised group had small increases during the competition phase, resulting in only a small difference between the long-term changes in box-squat 1RM (15.9%; ± 13.2%). The supervised group had further small increases in fat free mass resulting in a small difference (2.4%; ± 2.7%) in the long-term changes. The postconditioning differences between the 2 groups may have been a result of increased adherence and the attainment of higher training loads during supervised training. The lack of differences in strength after the competition period indicates that supervision should be maintained to reduce substantial decrements in performance.