Intra-amniotic ureaplasma infection : adverse outcomes vary depending on gestation

Background: Ureaplasmas are the most prevalent bacteria isolated from preterm deliveries and the prognosis for neonates varies depending on the gestation at delivery. Ureaplasmas vary their surface-exposed antigen (MBA, a virulence mechanism) during chronic intra-amniotic infections, but it is not known when changes first occur during gestation. Method: U. parvum serovar 3 (2x10e7CFU) was injected intra-amniotically (IA) into six experimental cohorts of pregnant ewes (of n=7), 3 days (d) or 7d before delivery at either: 100d, 124d or 140d gestation (term=145d). Control ewes received IA 10B broth. Fetuses were delivered surgically and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord. Ureaplasmas were tested by western blot to demonstrate MBA variation. Results: The highest number of ureaplasmas were recovered from FL at 100d gestation after 3 days of infection (p<0.03). Six of 7(86%) 100d–3d FL demonstrated an ureaplasma MBA variant, but only 17% and 15% of FL showed an MBA variant after 3d infection at 124d and 140d gestation respectively. Greatest variation of the MBA occurred in AF and FL at 124d gestation after 7d infection. The least MBA variation was observed at 140d; however, at this time the most severe histological chorioamnionitis was observed. Conclusions: After intra-amniotic ureaplasma injections, higher numbers of ureaplasmas gained access to the FL at 100d gestation than observed at later gestations. This may exacerbate the adverse outcomes for neonates delivered early in gestation. In late gestation, ureaplasma MBA variation was minimal, but chorioamnionitis was the most severe. Adverse pregnancy outcomes associated with IA ureaplasma infection may vary depending on the duration of gestation, the number of ureaplasmas isolated from the fetal tissues and the degree of MBA variation.

Implementation Guide for Surveillance of Clostridium Difficile Infection -- [Consultation Edition]

The Implementation Guide for hospital surveillance of Clostridium difficile infection (CDI) has been produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care (ACSQHC), and endorsed by the HAI Advisory Group. State jurisdictions and the ACSQHC have representatives on the Technical Working Group, and have had input into this document. (See acknowledgements on inside front cover)...

Implementation Guide for Surveillance of Central Line Associated Bloodstream Infection -- [Consultation Edition]

The implementation guide for the surveillance of CLABSI in intensive care units (ICU) was produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care(ACSQHC), and endorsed by the ACSQHC HAI Advisory Committee. State surveillance units, the ACSQHC and the Australian and New Zealand Intensive Care Society (ANZICS) have representatives on the Technical Working Group, and have provided input into this document.

Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma

Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC.

Re: Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin

Human papillomaviruses (HPVs) cause cervical cancer and some other types of epithelial cancers. HPV types from the phylogenic beta genus (beta-PVs), formerly known as epidermodysplasia verruciformis–associated HPV types, are frequently detected in nonmelanoma skin cancers, especially in squamous cell carcinomas (SCCs). An etiologic relationship with beta-PV infection is suspected...

Out of sight, out of mind/out of mind, out of site : Schooling and attention deficit hyperactivity disorder

Attention Deficit Hyperactivity Disorder is a diagnostic term now indelibly scored on the public psyche. In some quarters, a diagnosis of “ADHD” is regarded with derision. In others it is welcomed with relief. Despite intense multi-disciplinary research, the jury is still out with regards to the “truth” of ADHD. Not surprisingly, the rapid increase in diagnosis over the past fifteen years, coupled with an exponential rise in the prescription of restricted class psychopharmaceuticals has stirred virulent debate. Provoking the most interest, it seems, are questions regarding causality. Typically, these revolve around possible antecedents for “disorderly” behaviour – bad food, bad tv and bad parents. Very seldom is the institution of schooling ever in the line of sight. To investigate this gap, I draw on Foucault to question what might be happening in schools and how this may be contributing to the definition, recognition and classification of particular children as a particular kind of “disorderly”.

Mutual enlightenment : augmenting human factors research in surgical robotics

This discussion has outlined a theoretical and pragmatic framework to demonstrate that future research involving the analysis of human performance in surgical should encourage the use of phenomenology to enhance the knowledge base of this area of study. Merging experiential (first-person) and experimental (third-person) methods may possibly help improve research designs and analyses in the investigation of robotics in surgical performance. By relying solely on third-person techniques, the current methodology and interpretation used to analyze human performance in surgical robotics is limited. Recent advances in cognitive science and psychology have also recognized this limitation and have now begun to shift to neurophenomenology. Finally, discussion on recent robotics research presented here demonstrates the potential phenomenology holds for augmenting the methodological and analysis techniques currently used by researchers of human performance in surgical robotics.

Procuring OSM : base-line models of off-site manufacture business processes in Australia

A pressing cost issue facing construction is the procurement of off-site pre-manufactured assemblies. In order to encourage Australian adoption of off-site manufacture (OSM), a new approach to underlying processes is required. The advent of object oriented digital models for construction design assumes intelligent use of data. However, the construction production system relies on traditional methods and data sources and is expected to benefit from the application of well-established business process management techniques. The integration of the old and new data sources allows for the development of business process models which, by capturing typical construction processes involving OSM, provides insights into such processes. This integrative approach is the foundation of research into the use of OSM to increase construction productivity in Australia. The purpose of this study is to develop business process models capturing the procurement, resources and information flow of construction projects. For each stage of the construction value chain, a number of sub-processes are identified. Business Process Modelling Notation (BPMN), a mainstream business process modelling standard, is used to create base-line generic construction process models. These models identify OSM decision-making points that could provide cost reductions in procurement workflow and management systems. This paper reports on phase one of an on-going research aiming to develop a proto-type workflow application that can provide semi-automated support to construction processes involving OSM and assist in decision-making in the adoption of OSM thus contributing to a sustainable built environment.

Re-use of domain knowledge to provide confidence for adoption of off-site manufacturing for construction in Australia

Many construction industry decision-makers believe there is a lack of off-site manufacture (OSM) adoption for non-residential construction in Australia. Identification of construction business process was considered imperative in order to assist decision-makers to increase OSM utilisation. The premise that domain knowledge can be re-used to provide an intervention point in the construction process led a team of researchers to construct simple base-line process models for the complete construction process, segmented into six phases. Sixteen domain knowledge industry experts were asked to review the construction phase base-line models to answer the question “Where in the process illustrated by this base-line model phase is an OSM task?”. Through an iterative and generative process a number of off-site manufacture intervention points were identified and integrated into the process models. The re-use of industry expert domain knowledge provided suggestions for new ways to do basic tasks thus facilitating changes to current practice. It is expected that implementation of the new processes will lead to systemic industry change and thus a growth in productivity due to increased adoption of OSM.

Genetic variability and antimicrobial resistance of Ureaplasma parvum in response to maternal erythromycin treatment : a study in pregnant sheep

Background: Ureaplasmas are the most frequently isolated microorganisms from the amniotic fluid (AF) of pregnant women and can cause chronic infections that are difficult to eradicate with standard macrolide treatment. We tested the effects of erythromycin treatment on phenotypic and genotypic markers of ureaplasmal antimicrobial resistance in sheep. Method: At 50 days of gestation (d, term=145d) 12 pregnant ewes received intra-amniotic injections of U. parvum serovar 3 (erythromycin-sensitive, 2x104 colony-forming-units). At 100d ewes received: erythromycin treatment (500 mg, q3h for 4 days, IM, n=6) or no treatment (n=6). Fetuses were delivered surgically (125d) and AF and chorioamnion were collected for: culture, minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) testing; 23S rRNA sequencing; and detection of macrolide-lincosamide-streptogramin resistance (MLSr) genes. Results: MICs of erythromycin, azithromycin and roxithromycin against AF isolates were low (range = 0.06 mg/L to 1.0 mg/L); however, chorioamnion isolates demonstrated increased resistance to roxithromycin (0.13 – 5.33 mg/L). 62.5% of chorioamnion ureaplasmas formed biofilms in vitro and mutations (125 nucleotides, 29.6%) were found in the 23S rRNA gene (domain V) of chorioamnion (but not AF) ureaplasmas. MLSr genes (ermB, msrC and msrD) were detected in 100% of chorioamnion isolates and only msrD was detected in AF isolates (40%). Conclusions: 23S rRNA mutations and MLSr genes occurred independently of erythromycin treatment, suggesting that the anatomical site of infection and microenvironment may exert selective pressures on ureaplasmas that cause genetic changes and alter antimicrobial sensitivity profiles. These results have serious implications for treatment of in utero infections.

Ureaplasma parvum serovar 3 multiple banded antigen size variation after chronic intra-amniotic infection/colonization

Ureaplasma species are the microorganisms most frequently associated with adverse pregnancy outcomes. The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a key virulence factor of ureaplasmas. The MBA demonstrates size variation, which we have shown previously to be correlated with the severity of chorioamnion inflammation. We aimed to investigate U. parvum serovar 3 pathogenesis in vivo, using a sheep model, by investigating: MBA variation after long term (chronic) and short term (acute) durations of in utero ureaplasma infections, and the severity of chorioamnionitis and inflammation in other fetal tissues. Inocula of 2x107 colony-forming-units (CFU) of U. parvum serovar 3 (Up) or media controls (C) were injected intra-amniotically into pregnant ewes at one of three time points: day 55 (69d Up, n=8; C69, n=4); day 117 (7d Up, n=8; C7, n=2); and day 121 (3d Up, n=8; C3, n=2) of gestation (term=145-150d). At day 124, preterm fetuses were delivered surgically. Samples of chorioamnion, fetal lung, and umbilical cord were: (i) snap frozen for subsequent ureaplasma culture, and (ii) fixed, embedded, sectioned and stained by haematoxylin and eosin stain for histological analysis. Selected fetal lung clinical ureaplasma isolates were cloned and filtered to obtain cultures from a single CFU. Passage 1 and clone 2 ureaplasma cultures were tested by western blot to demonstrate MBA variation. In acute durations of ureaplasma infection no MBA variants (3d Up) or very few MBA variants (7d Up) were present when compared to the original inoculum. However, numerous MBA size variants were generated in vivo (alike within contiguous tissues, amniotic fluid and fetal lung, but different variants were present within chorioamnion), during chronic, 69d exposure to ureaplasma infection. For the first time we have shown that the degree of ureaplasma MBA variation in vivo increased with the duration of gestation.

Mid-gestation intra-amniotic infection with Ureaplasma parvum is resolved within spiny mice (Acomys cahirinus) by term delivery: but caused chronic infection of fetal lungs and placentae

Background: Ureaplasma species in amniotic fluid at the time of second-trimester amniocentesis increases the risk of preterm birth, but most affected pregnancies continue to term (Gerber et al. J Infect Dis 2003). We aimed to model intra-amniotic (IA) ureaplasma infection in spiny mice, a species with a relatively long gestation (39 days) that allows investigation of the disposition and possible clearance of ureaplasmas in the feto-placental compartment. Method: Pregnant spiny mice received IA injections of U. parvum serovar 6 (10µL, 1x104 colony-forming-units in PBS) or 10B media (10µL; control) at 20 days (d) of gestation (term=39d). At 37d fetuses (n=3 ureaplasma, n=4 control) were surgically delivered and tissues were collected for; bacterial culture, ureaplasma mba and urease gene expression by PCR, tissue WBC counts and indirect fluorescent antibody (IFA) staining using anti-ureaplasma serovar 6 (rabbit) antiserum. Maternal and fetal plasma IgG was measured by Western blot. Results: Ureaplasmas were not detected by culture or PCR in fetal or maternal tissues but were visualized by IFA within placental and fetal lung tissues, in association with inflammatory changes and elevated WBC counts (p<0.0001). Anti-ureaplasma IgG was detected in maternal (2/2 tested) and fetal (1/2 tested) plasma but not in controls (0/3). Conclusions: IA injection of ureaplasmas in mid-gestation spiny mice caused persistent fetal lung and placental infection even though ureaplasmas were undetectable using standard culture or PCR techniques. This is consistent with resolution of IA infection, which may occur in human pregnancies that continue to term despite detection of ureaplasmas in mid-gestation.