Estimation of fetal and effective dose for CT examinations

Doses from CT examinations are difficult to estimate. However, they are requested more frequently due to the increase in CT examinations. In particular, fetal dose estimations are frequently required for patients who have discovered, subsequent to the examination, that they were pregnant when the examination was conducted. A computer model has been developed to facilitate such dose calculations. This model combines empirical beam data with anatomical information. The model has been verified using thermoluminescent dosemeter (TLD) readings of internal and surface dose from both phantoms and patients, including intrauterine doses for patients undergoing afterloading gynaecological intracavitary treatment. Although only limited experimental data were available, the results indicate that the model accurately predicts uterine doses within acceptable errors. This approach has been validated for fetal dose estimation. The model was also used in a comparison with the nationally available CT dose data from the National Radiological Protection Board (NRPB). The two models were found to be in agreement for fetal dose estimations.

Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats

OBJECTIVE: Progesterone (P4) plays a central role in women's health. Synthetic progestins are used clinically in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Unfortunately, synthetic progestins are associated with side effects, including cardiovascular disease and breast cancer. Botanical dietary supplements are widely consumed for the alleviation of a variety of gynecological issues, but very few studies have characterized natural compounds in terms of their ability to bind to and activate progesterone receptors (PR). Kaempferol is a flavonoid that functions as a non-steroidal selective progesterone receptor modulator (SPRM) in vitro. This study investigated the molecular and physiological effects of kaempferol in the ovariectomized rat uteri.

METHODS: Since genistein is a phytoestrogen that was previously demonstrated to increase uterine weight and proliferation, the ability of kaempferol to block genistein action in the uterus was investigated. Analyses of proliferation, steroid receptor expression, and induction of well-established PR-regulated targets Areg and Hand2 were completed using histological analysis and qPCR gene induction experiments. In addition, kaempferol in silico binding analysis was completed for PR. The activation of estrogen and androgen receptor signalling was determined in vitro.

RESULTS: Molecular docking analysis confirmed that kaempferol adopts poses that are consistent with occupying the ligand-binding pocket of PRA. Kaempferol induced expression of PR regulated transcriptional targets in the ovariectomized rat uteri, including Hand2 and Areg. Consistent with progesterone-l ke activity, kaempferol attenuated genistein-induced uterine luminal epithelial proliferation without increasing uterine weight. Kaempferol signalled without down regulating PR expression in vitro and in vivo and without activating estrogen and androgen receptors.

CONCLUSION: Taken together, these data suggest that kaempferol is a unique natural PR modulator that activates PR signaling in vitro and in vivo without triggering PR degradation.

HPV16 Down-Regulates the Insulin-Like Growth Factor Binding Protein 2 to Promote Epithelial Invasion in Organotypic Cultures

Cervical cancer is a multi-stage disease caused by human papillomaviruses (HPV) infection of cervical epithelial cells, but the mechanisms regulating disease progression are not clearly defined. Using 3-dimensional organotypic cultures, we demonstrate that HPV16 E6 and E7 proteins alter the secretome of primary human keratinocytes resulting in local epithelial invasion. Mechanistically, absence of the IGF-binding protein 2 (IGFBP2) caused increases in IGFI/II signalling and through crosstalk with KGF/FGFR2b/AKT, cell invasion. Repression of IGFBP2 is mediated by histone deacetylation at the IGFBP2 promoter and was reversed by treatment with histone deacetylase (HDAC) inhibitors. Our in vitro findings were confirmed in 50 invasive cancers and 79 cervical intra-epithelial neoplastic lesions caused by HPV16 infection, where IGFBP2 levels were reduced with increasing disease severity. In summary, the loss of IGFBP2 is associated with progression of premalignant disease, and sensitises cells to pro-invasive IGF signalling, and together with stromal derived factors promotes epithelial invasion.

Pharmacokinetics of melatonin in preterm infants

Aims: Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials. Methods: Melatonin was administered to 18 preterm infants in doses ranging from 0.04-0.6μgkg^-1 over 0.5-6h. Pharmacokinetic profiles were analyzed individually and by population methods. Results: Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1μgkg^-1h^-1 for 2h showed a median half-life of 15.82h and median maximum plasma concentration of 203.3pgml^-1. On population pharmacokinetics, clearance was 0.045lh^-1, volume of distribution 1.098l and elimination half-life 16.91h with gender (P = 0.047) and race (P < 0.0001) as significant covariates. Conclusions: A 2h infusion of 0.1μgkg^-1h^-1 increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants. © 2013 The British Pharmacological Society.

A review of the welfare of dairy cows in continuously housed and pasture-based production systems.

There is increasing interest in the use of continuous housing systems for dairy cows, with various reasons put forward to advocate such systems. However, the welfare of dairy cows is typically perceived to be better within pasture-based systems, although such judgements are often not scientifically based. The aim of this review was to interrogate the existing scientific literature to compare the welfare, including health, of dairy cows in continuously housed and pasture-based systems. While summarising existing work, knowledge gaps and directions for future research are also identified. The scope of the review is broad, examining relevant topics under three main headings; health, behaviour, and physiology. Regarding health, cows on pasture-based systems had lower levels of lameness, hoof pathologies, hock lesions, mastitis, uterine disease, and mortality compared to cows on continuously housed systems. Pasture access also had benefits for dairy cow behaviour, in terms of grazing, improved lying / resting times, and lower levels of aggression. Moreover, when given the choice between pasture and indoor housing, cows showed an overall preference for pasture, particularly at night. However, the review highlighted the need for a deeper understanding of cow preference and behaviour. Potential areas for concern within pasture-based systems included physiological indicators of more severe negative energy balance, and in some situations, the potential for compromised welfare with exposure to unpredictable weather conditions. In summary, the results from this review highlight that there remain considerable animal welfare benefits from incorporating pasture access into dairy production systems.

Siblings’ Sex is linked to Mental Rotation Performance in Males but not Females

Research has consistently found sex differences in mental rotation. Twin research has suggested that females with male co-twins perform better than females with female co-twins on mental rotation. Because twins share both pre-natal and post-natal environments, it is not possible to test whether this advantage is due to in-uterine transmission of testosterone from males to females or due to socialisation processes. The present study explored whether the advantage of females with brothers can be observed in non-twin siblings. Participants (N = 1799) were assessed on mental rotation. The observed group differences were overall small: males performed significantly better than females; females with sisters performed similarly to females with brothers; importantly, males with brothers performed significantly better than both female groups. The results suggest that sex differences in mental rotation are driven by the group of males with brothers.