Maternal parity affects neonatal survival rate in a colony of captive bred baboons (Papio hamadryas)

Background Non‐human primates, particularly baboons, are valuable as animal models for reproductive research, because of their similarity to humans. Knowledge of colony‐specific pregnancy and neonatal outcomes is essential for interpretation of such research. Methods A retrospective review of the reproductive records of the Australian National Baboon Colony (ANBC) from 1994 to 2006 was performed. Results The overall live birth rate was over 70% of recognized pregnancies. Pregnancy loss was due to equal proportions of spontaneous abortion and stillbirth, and was not affected by maternal age or parity. Stillbirth rates were increased by the use of animals in novel late pregnancy experimental protocols. Neonatal mortality rates were low overall, but significantly higher in primiparous compared with multiparous mothers (P < 0.05). There were no cases of maternal mortality. Conclusions The success of the ANBC breeding programme is demonstrated by the low rate of pregnancy loss, high neonatal survival rate and lack of maternal mortality.     

Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.     

In vitro zygotic embryo culture of wild Musa acuminata ssp.malaccensis and factors affecting germination and seedling growth

In vitro zygotic embryo culture of wild banana significantly increased the germination compared to greenhouse grown seeds. Embryo orientation and BAP concentration significantly affected germination rate. These factors together with gelling agent, dark and light conditions and coconut water, also showed variable effects on the number of roots per plant, root length, shoot length, number of days to root emergence and number of days to shoot emergence.     

Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy

Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch). Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited.     

Heart rate recovery and heart rate complexity following resistance exercise training and detraining in young men

The purpose of this study was to examine heart rate recovery (HRR) and linear/nonlinear heart rate variability (HRV) before and after resistance training. Fourteen young men (25.0 +/- 1.1 yr of age) completed a crossover design consisting of a 4-wk time-control period, 6 wk of resistance training (3 days/wk), and 4 wk of detraining. Linear HRV was spectrally decomposed using an autoregressive approach. Nonlinear dynamics of heart rate complexity included sample entropy (SampEn) and Lempel-Ziv entropy (LZEn). HRR was calculated from a graded maximal exercise test as maximal heart rate attained during the test minus heart rate at 1 min after exercise (HRR). There was no change in SampEn, LZEn, or HRR after the time-control portion of the study (P > 0.05). SampEn (P < 0.05), LZEn (P < 0.05), and HRR (P < 0.05) increased after resistance training and returned to pretraining values after detraining. There was no change in spectral measures of HRV at any time point (P > 0.05). These findings suggest that resistance exercise training increases heart rate complexity and HRR after exercise but has no effect on spectral measures of HRV in young healthy men. These autonomic changes regress shortly after cessation of training.     

Do “Virtual” and “Outpatient” Public Health Tuberculosis Clinics Perform Equally Well? A Program-Wide Evaluation in Alberta,Canada

Background

Meeting the challenge of tuberculosis (TB) elimination will require adopting new models of delivering patient-centered care customized to diverse settings and contexts. In areas of low incidence with cases spread out across jurisdictions and large geographic areas, a “virtual” model is attractive. However, whether “virtual” clinics and telemedicine deliver the same outcomes as face-to-face encounters in general and within the sphere of public health in particular, is unknown. This evidence is generated here by analyzing outcomes between the “virtual” and “outpatient” public health TB clinics in Alberta, a province of Western Canada with a large geographic area and relatively small population.

Methods

In response to the challenge of delivering equitable TB services over long distances and to hard to reach communities, Alberta established three public health clinics for the delivery of its program: two outpatient serving major metropolitan areas, and one virtual serving mainly rural areas. The virtual clinic receives paper-based or electronic referrals and generates directives which are acted upon by local providers. Clinics are staffed by dedicated public health nurses and university-based TB physicians. Performance of the two types of clinics is compared between the years 2008 and 2012 using 16 case management and treatment outcome indicators and 12 contact management indicators.

Findings

In the outpatient and virtual clinics, respectively, 691 and 150 cases and their contacts were managed. Individually and together both types of clinics met most performance targets. Compared to outpatient clinics, virtual clinic performance was comparable, superior and inferior in 22, 3, and 3 indicators, respectively.

Conclusions

Outpatient and virtual public health TB clinics perform equally well. In low incidence settings a combination of the two clinic types has the potential to address issues around equitable service delivery and declining expertise.     

Genomic Comparison of the Closely-Related Salmonella enterica Serovars Enteritidis,Dublin and Gallinarum

The Salmonella enterica serovars Enteritidis, Dublin, and Gallinarum are closely related but differ in virulence and host range. To identify the genetic elements responsible for these differences and to better understand how these serovars are evolving, we sequenced the genomes of Enteritidis strain LK5 and Dublin strain SARB12 and compared these genomes to the publicly available Enteritidis P125109, Dublin CT 02021853 and Dublin SD3246 genome sequences. We also compared the publicly available Gallinarum genome sequences from biotype Gallinarum 287/91 and Pullorum RKS5078. Using bioinformatic approaches, we identified single nucleotide polymorphisms, insertions, deletions, and differences in prophage and pseudogene content between strains belonging to the same serovar. Through our analysis we also identified several prophage cargo genes and pseudogenes that affect virulence and may contribute to a host-specific, systemic lifestyle. These results strongly argue that the Enteritidis, Dublin and Gallinarum serovars of Salmonella enterica evolve by acquiring new genes through horizontal gene transfer, followed by the formation of pseudogenes. The loss of genes necessary for a gastrointestinal lifestyle ultimately leads to a systemic lifestyle and niche exclusion in the host-specific serovars.     

Salmonella serotypes isolated from pet chews in New Zealand

AIMS: To survey the prevalence of Salmonella in imported and domestic pet chews for assessing their potential in introducing novel pathogenic and antimicrobial resistant Salmonella serotype clones into New Zealand, and as vehicles of salmonellosis in the domestic home environment. METHODS AND RESULTS: Three hundred samples, each of imported and domestic pet chews, were examined bacteriologically for the presence of Salmonella. Salmonella cells in the pre-enrichment culture were concentrated by using Dynabeads, and then selective enrichment and plating were performed by a method described in the Bacteriological and Analytical Manual, USFDA. Salmonella was isolated from 16 (5.3%) of the imported and 20 (6.7%) of the domestic pet chews, but the prevalences of Salmonella in imported and domestic products were not significantly different. All Salmonella isolates were serotyped and genotyped by pulsed-field gel electrophoresis and antimicrobial susceptibility determined by the Clinical and Laboratory Standards Institute disc diffusion methods. Salmonella Borreze has never been recorded earlier in New Zealand and was detected from Australian raw hide. Three isolates of Salmonella London were resistant to ampicillin and gentamicin, and two isolates of Salmonella Infantis were resistant to nalidixic acid, one of which was also resistant to streptomycin. CONCLUSIONS: Novel pathogenic and antimicrobial-resistant Salmonella are being introduced into New Zealand through the import of pet chews. This indicates that pet chews are a potential source of exposure to Salmonella in the domestic home environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Contaminated pet chews are potential sources of Salmonella infection for domestic pets, and humans are at risk of exposure either directly by contact through handling or inadvertently by cross-contamination of food or food-contact surfaces in home environments.     

Biomarker Development for the Clinical Activity of the mTOR Inhibitor Everolimus (RAD001): Processes,Limitations, and Further Proposals

The mTOR inhibitor everolimus (RAD001, Afinitor) is an orally active anticancer agent. Everolimus demonstrates growth-inhibitory activity against a broad range of tumor cell histotypes in vitro and has the capacity to retard tumor growth in preclinical tumor models in vivo through mechanisms directed against both the tumor cell and the solid tumor stroma components. These properties have rendered it to be a clinically active drug, with subsequent registration in renal cell carcinoma (Motzer et al. [2008]. Lancet 372, 449–456) as well as showing strong potential as a combination partner (André F et al. [2008]. J Clin Oncol 26. Abstract 1003). Although everolimus has a high specificity for its molecular target, the ubiquitous nature of mTOR and the multifactorial influence that mTOR signaling has on cell physiology have made studies difficult on the identification and validation of a biomarker set to predict and monitor drug sensitivity for clinical use. In this review, a summary of the preclinical and clinical data relevant to biomarker development for everolimus is presented, and the advantages and problems of current biomarkers are reviewed. In addition, alternative approaches to biomarker development are proposed on the basis of examples of a combination of markers and functional noninvasive imaging. In particular, we show how basal levels of pAKT and pS6 together could, in principle, be used to stratify patients for likely response to an mTOR inhibitor.