Mouse models of colorectal cancer as preclinical models.

In this review, we discuss the application of mouse models to the identification and pre-clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large-scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross-species comparative 'omics-based approaches to this problem. We highlight recent progress in modelling late-stage disease using mice, and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection.REM, SJAB, MJA and DJA are funded by Cancer Research UK.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/bies.20150003

How can we reduce the risk of mother-to-child transmission of HIV during invasive obstetric procedures?

Antenatal invasive obstetric procedures may be diagnostic or therapeutic, and are performed at different stages of pregnancy for various indications. The most common indication for an invasive procedure during pregnancy is for fetal karyotyping when a chromosomal abnormality or a genetic defect is suspected, either from the couple’s history or from ultrasound assessment of the fetus. Other less common but equally important indications may be diagnostic (fetoscopy, fetal tissue sampling, estimation of fetal haemoglobin) or therapeutic (aspiration of various fetal cavities, fetal blood transfusion and embryo reductions). In a high HIV prevalence setting like South Africa, a significant proportion of pregnant women in need of invasive procedures will be HIV-infected

Chlamydia trachomatis Biovar L2 Infection in Women in South Africa

We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified

Comparative uptake of fluoride ion into enamel from various topical fluorides in vitro

The document attached has been archived with permission from the Australian Dental Association (8 March 2008). An external link to the publisher’s copy is included.Background: There are many forms of topical fluoride available today, making the decision as to which is most effective to manage the immediate caries risk problem at hand, very difficult. The objective of this project was to determine the concentration and pattern of fluoride ion uptake into enamel from a variety of categories of topical fluoride recently available in Australia. Methods: Extracted, intact molar teeth were sectioned to provide six plates of smooth surface enamel. Windows of enamel 2 x 6mm were exposed to a variety of topical fluorides for periods simulating those used in vivo. Following drying, the slates of enamel were exposed to 2ml of 0.1M HCl as a chemical biopsy agent for incremental periods of time. The concentrations of fluoride ion in the biopsy solutions for both test and background (control) slates of enamel were determined directly using a fluoride combination selective electrode in conjunction with a high impedance pH meter. Cumulative amounts of fluoride were determined for each topical fluoride agent. Results: The concentrations of fluoride ion taken up into enamel were generally proportional to those present in each agent. However, those from APF gel greatly exceeded the amounts taken up from NaF gel. Also, the concentrations taken up from some of the highly concentrated metal fluorides were surprisingly low. Prior etching of enamel increased uptake and prolonged application of APF gel provided no extra benefit. Conclusions: Some topical fluorides, e.g., APF gel, provided a greatly increased uptake and to a greater depth than other self-application products. However, the frequency of its use should be considered with caution where patients have glassbased restorations.N Pai, J McIntyre, N Tadic and C Laparidi

Exploration of the Mid-Cayman Rise

Oceanography articles are licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution, and reproduction in any medium or format as long as users cite the materials appropriately (e.g., authors, Oceanography, volume number, issue number, page number[s], figure number[s], and DOI for the article), provide a link to the Creative Commons license, and indicate the changes that were made to the original content

Antiretroviral Strategies to Prevent Mother-to-Child Transmission of HIV: Striking a Balance between Efficacy, Feasibility, and Resistance

Dara Lehman and colleagues discuss a randomized trial that found that adding up to a week of twice-daily zidovudine+lamivudine to single-dose nevirapine reduces the risk of resistance in mothers and infants

How to suppress undesired synchronization

It is delightful to observe the emergence of synchronization in the blinking of fireflies to attract partners and preys. Other charming examples of synchronization can also be found in a wide range of phenomena such as, e.g., neurons firing, lasers cascades, chemical reactions, and opinion formation. However, in many situations the formation of a coherent state is not pleasant and should be mitigated. For example, the onset of synchronization can be the root of epileptic seizures, traffic congestion in communication networks, and the collapse of constructions. Here we propose the use of contrarians to suppress undesired synchronization. We perform a comparative study of different strategies, either requiring local or total knowledge of the system, and show that the most efficient one solely requires local information. Our results also reveal that, even when the distribution of neighboring interactions is narrow, significant improvement in mitigation is observed when contrarians sit at the highly connected elements. The same qualitative results are obtained for artificially generated networks as well as two real ones, namely, the Routers of the Internet and a neuronal network

Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

A comparison of medium-term heat acclimation by post-exercise hot water immersion or exercise in the heat: Adaptations, overreaching, and thyroid hormones.

This research compared thermal and perceptual adaptations, endurance capacity, and overreaching markers in men after 3, 6, and 12-days of post-exercise hot water immersion (HWI) or exercise heat acclimation (EHA) with a temperate exercise control (CON), and examined thyroid hormones as a mechanism for the reduction in resting and exercising core temperature (Tre) after HWI. HWI involved a treadmill run at 65% V̇O2peak in 19°C followed by a 40°C bath. EHA and CON involved a work-matched treadmill run at 65% V̇O2peak in 33°C or 19°C, respectively. Compared with CON, resting mean body temperature (Tb), resting and end-exercise Tre, Tre at sweating onset, thermal sensation and perceived exertion were lower and whole-body sweat rate (WBSR) was higher after 12-days of HWI (all P ≤ 0.049, resting Tb: CON -0.11 ± 0.15°C, HWI -0.41 ± 0.15°C). Moreover, resting Tb and Tre at sweating onset were lower after HWI than EHA (P ≤ 0.015, resting Tb: EHA -0.14 ± 0.14°C). No differences were identified between EHA and CON (P ≥ 0.157) except WBSR which was greater after EHA (P = 0.013). No differences were observed between interventions for endurance capacity or overreaching markers (mood, sleep, Stroop, P ≥ 0.190). Thermal adaptations observed after HWI were not related to changes in thyroid hormone concentrations (P ≥ 0.086). In conclusion, 12-days of post-exercise hot water immersion conferred more complete heat acclimation than exercise heat acclimation without increasing overreaching risk, and changes in thyroid hormones are not related to thermal adaptationsafter post-exercise hot water immersion