Gestational Exposure to Perchlorate in the Rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain.

Iodine is essential for the production of thyroid hormones. Perchlorate is an environmental contaminant that interferes with iodine uptake into the thyroid gland to reduce thyroid hormone synthesis. As thyroid hormones are critical for brain development, exposure to perchlorate during pregnancy is of concern for the developing fetal brain. In this study, we (1) define profiles of thyroid hormone in the maternal and fetal compartments of pregnant rats in response to inhibition of the sodium-iodide symporter (NIS) by perchlorate and (2) expand inquiry previously limited to serum to include fetal thyroid gland and brain. Perchlorate was added to the drinking water (0, 1, 30, 300, and 1000 ppm) of pregnant rat dams from gestational days (GD) 6-20. On GD20, blood, thyroid gland, and brain were collected from the fetus and dam for thyroid hormone and molecular analyses. Thyroid gland and serum thyroid hormones were dose-dependently reduced, with steeper declines evident in the fetus than in the dam. The thyroid gland revealed perturbations of thyroid hormone-action with greater sensitivity in the fetus than the dam. Thyroid hormones and thyroid hormone-responsive gene expression were reduced in the fetal cortex portending effects on brain development. These findings are the first quantitative assessments of perchlorate-induced deficits in the fetal thyroid gland and fetal brain. We provide a conceptual framework to develop a quantitative NIS adverse outcome pathway for serum thyroid hormone deficits and the potential to impact the fetal brain. Such a framework may also serve to facilitate the translation of in vitro bioactivity to the downstream in vivo consequences of NIS inhibition in the developing fetus.

Incidental mucocutaneous cytomegalovirus detection and its predictive value for systemic disease.

Multiplex polymerase chain reaction (PCR) testing has revolutionised microbiological practice but also increased the number of positive results of uncertain significance. This phenomenon has been seen in the increasing detection of cytomegalovirus (CMV) in mucocutaneous swabs for herpesviruses, the microbiological significance of which is a priori unclear. The aim of our study was to determine if an incidental finding of a positive CMV result represented CMV disease, if it facilitated a timely diagnosis of CMV disease or whether there were any deleterious outcomes. We performed a retrospective review of patients with an incidentally positive PCR result for CMV on external and mucosal swabs, including medical comorbidities and presence of immunosuppression, subsequent investigations, whether a diagnosis of CMV disease was made, and treatment. CMV detection was infrequent, detected in 158 (3.4%) of 4626 herpes multiplex PCR tests performed. The majority (60.4%) of patients were immunocompromised, and amongst these patients a positive swab represented a new diagnosis or already known CMV disease in 14%. In seven patients (5%), all of whom were immunocompromised, the positive CMV PCR on a swab led to further investigation and subsequent diagnosis and treatment of CMV disease. Whilst not recommended for diagnosis of CMV disease, if CMV is detected on a mucocutaneous swab in an immunocompromised patient, further assessment and investigation for CMV disease should be undertaken.

Rifamycin derivatives active against pathogenic rapidly-growing mycobacteria.

Infections due to rapidly growing mycobacteria (RGM), and in particular the RGM species Mycobacterium abscessus (Mab), are very difficult to treat and reports on novel therapeutic options are scarce. A hallmark of all pathogenic RGM species is their resistance to the four first-line drugs used to treat infections with Mycobacterium tuberculosis including rifampicin. This study demonstrates that modification of the rifampicin scaffold can restore rifampicin activity against the three most commonly isolated pathogenic RGM species including Mab. We also note that the structure-activity relationship for Mab is different as compared to the non-pathogenic RGM species Mycobacterium smegmatis.

A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development.

Cortical heterotopias are clusters of ectopic neurons in the brain and are associated with neurodevelopmental disorders like epilepsy and learning disabilities. We have previously characterized the robust penetrance of a heterotopia in a rat model, induced by thyroid hormone (TH) disruption during gestation. However, the specific mechanism by which maternal TH insufficiency results in this birth defect remains unknown. Here we first determined the developmental window susceptible to endocrine disruption and describe a cellular mechanism responsible for heterotopia formation. We show that five days of maternal goitrogen treatment (10 ppm propylthiouracil) during the perinatal period (GD19-PN2) induces a periventricular heterotopia in 100% of the offspring. Beginning in the early postnatal brain, neurons begin to aggregate near the ventricles of treated animals. In parallel, transcriptional and architectural changes of this region were observed including decreased Sonic hedgehog (Shh) expression, abnormal cell adhesion, and altered radial glia morphology. As the ventricular epithelium is juxtaposed to two sources of brain THs, the cerebrospinal fluid and vasculature, this progenitor niche may be especially susceptible to TH disruption. This work highlights the spatiotemporal vulnerabilities of the developing brain and demonstrates that a transient period of TH perturbation is sufficient to induce a congenital abnormality.

Antenatal maternal hepatitis B care is a predictor of timely perinatal administration of hepatitis B immunoglobulin.

BACKGROUND: Mother-to-child transmission of hepatitis B virus continues to occur despite universal recommendations for neonatal immune prophylaxis therapy (IPT) and infant vaccination. AIM: To characterise the risk factors for failure to provide timely IPT and completion of the infant hepatitis B vaccination schedule for children born to mothers with chronic hepatitis B (CHB). METHODS: We conducted a retrospective cohort study to assess compliance with universal guidelines for neonatal IPT for children born to CHB mothers at Monash Health, Australia from 2008 to 2013. These mothers were invited to participate in a telephone interview regarding post-partum hepatitis B virus (HBV) care and infant vaccination status. Multivariate logistic regression analysis was utilised to identify the predictors for engagement with specialist HBV care, timely administration of IPT, completion of HBV vaccination schedule and serological testing of the baby. RESULTS: A total of 451 CHB mothers delivered 454 live births. HBV immunoglobulin (HBIg) was dispensed within 12 h in 79.52% of births. HBIg was not administered to eight neonates. Of the 451 women, 125 were interviewed: 88.8% of babies completed the vaccine schedule, and 19.2% of infants had post-vaccination testing. Antenatal HBV care was independently associated with a greater likelihood of timely HBIg administration (odds ratio 1.64, P = 0.04, 95% CI: 1.03-2.61). There were no significant predictors for engagement with specialist HBV care, vaccine coverage or serological testing of the baby. CONCLUSION: Targeted interventions to improve timely HBIg and completion of the vaccine schedule are recommended. All pregnant women with CHB should be referred for HBV-specific antenatal care regardless of viral replicative status.

Assessment of Movement Patterns during Intubation between Novice and Experienced Providers Using Mobile Sensors: A Preliminary, Proof of Concept Study.

BACKGROUND: There are likely marked differences in endotracheal intubation (ETI) techniques between novice and experienced providers. We performed a proof of concept study to determine if portable motion technology could identify the motion components of ETI between novice and experienced providers. METHODS: We recruited a sample of novice and experienced providers to perform ETIs on a cadaver. Their movements during ETI were recorded with inertial measurement units (IMUs) on the left wrist. The signals were assessed visually between novice and experienced providers to identify areas of differences at key steps during ETI. We then calculated spectral smoothness (SS), a quantitative measure inversely related to movement variability, for all ETI attempts. RESULTS: We enrolled five novice and five experienced providers. When visually inspecting the data, we noted maximum variability when inserting the blade of the laryngoscope into the mouth and while visualizing the glottic opening. Novice providers also had greater overall variability in their movement patterns (SS novice 6.4 versus SS experienced 26.6). CONCLUSION: Portable IMUs can be used to detect differences in movement patterns between novice and experienced providers in cadavers. Future ETI educational efforts may utilize portable IMUs to help accelerate the learning curve of novice providers.