Human health risk assessment for silver catfish Schilbe intermedius Rüppell, 1832, from two impoundments in the Olifants River, Limpopo, South Africa

As rural populations grow and rural poverty increases, consumption of fish from contaminated river systems will increase to supplement dietary protein requirements. The concentrations of metals in fish muscle tissue at two impoundments of the Olifants River (Flag Boshielo Dam and the Phalaborwa Barrage) were measured, and a human health risk assessment following Heath et al. (2004) conducted to investigate whether consumption of Schilbe intermedius from these impoundments posed a risk to human health. The results confirmed that metals are accumulating in the muscle tissue of S. intermedius. No patterns were observed in the ratios of the metals bio-accumulated at each impoundment. The human health risk assessment identified that all fish analysed exceeded the recommended levels for safe consumption for lead and chromium and about 50% exceeded the recommended level for antimony at Flag Boshielo Dam. Almost all fish analysed exceeded the recommended level for lead and more than 50% exceeded the recommended level for arsenic at the Phalaborwa Barrage. We conclude that weekly consumption of S. intermedius from these impoundments may pose an unacceptable risk to the health of rural communities.Keywords: risk assessment, human health, Schilbe intermedius, lead, chromium, antimon

Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice

Development Of An Age-Frequency Distribution For Ocean Quahogs (Arctica Islandica) On Georges Bank

Ocean quahogs [Arctica islandica (Linnaeus, 1769)] are the longest-lived, noncolonial animal known today, with a maximum life span exceeding 500 y. Ocean quahogs are a commercially important bivalve, inhabiting the continental shelf of the North Atlantic Basin. Although considerable information exists on the growth and physiology of A. islandica, limited information is available regarding recruitment; accordingly, sustainably managing the fishery is a challenge. To investigate long-termrecruitment trends, the age of ocean quahogs fromGeorges Bank which were fully recruited to the commercial fishery (\u3e80 mm shell length) was determined by analysis of annual growth lines in the hinge plate. Ages of animals representing the fully recruited size range were used to develop an age-length key, enabling reconstruction of the population age frequency. The population age frequency showed that the Georges Bank population experienced an increase in recruitment beginning in the late 1890s. Initial settlement, documented by a few ocean quahogs that were much older, occurred much earlier, in the early 1800s. Following the late 1890s increase in recruitment, the population expanded rapidly reaching carrying capacity in 20-30 y. Recruitment was more or less continuous after this expansion, consistent with maintenance of a population at carrying capacity. Unusually large year classes were not observed, nor were significant periods of high recruitment interspersed with periods of low recruitment. The relationship of growth rate with age for the oldest clams was assessed using the time series of yearly growth increments and the resulting relationship fitted to three models (von Bertalanffy, Gompertz, and Tanaka\u27s ALOG curve). The ALOG model was clearly superior because it allows for persistent indeterminate growth at old age, rather than the asymptotic behavior of the other two and because it allows for a rapid change in growth rate at what is presumed to be maturity

New roles for nuclear receptors in prostate cancer

Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease - hence the quest for new effective therapies for "castrate-resistant" prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC. The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This reviews aims to provide a snapshot of current knowledge of the roles of different nuclear receptors in prostate cancer, a rapidly-evolving field of research

Evaluation of neurotoxicity and long-term function and behavior following intrathecal 1 % 2-chloroprocaine in juvenile rats

Spinally-administered local anesthetics provide effective perioperative anesthesia and/or analgesia for children of all ages. New preparations and drugs require preclinical safety testing in developmental models. We evaluated age-dependent efficacy and safety following 1 % preservative-free 2-chloroprocaine (2-CP) in juvenile Sprague-Dawley rats. Percutaneous lumbar intrathecal 2-CP was administered at postnatal day (P)7, 14 or 21. Mechanical withdrawal threshold pre- and post-injection evaluated the degree and duration of sensory block, compared to intrathecal saline and naive controls. Tissue analyses one- or seven-days following injection included histopathology of spinal cord, cauda equina and brain sections, and quantification of neuronal apoptosis and glial reactivity in lumbar spinal cord. Following intrathecal 2-CP or saline at P7, outcomes assessed between P30 and P72 included: spinal reflex sensitivity (hindlimb thermal latency, mechanical threshold); social approach (novel rat versus object); locomotor activity and anxiety (open field with brightly-lit center); exploratory behavior (rearings, holepoking); sensorimotor gating (acoustic startle, prepulse inhibition); and learning (Morris Water Maze). Maximum tolerated doses of intrathecal 2-CP varied with age (1.0 μL/g at P7, 0.75 μL/g at P14, 0.5 μL/g at P21) and produced motor and sensory block for 10−15 min. Tissue analyses found no significant differences across intrathecal 2-CP, saline or naïve groups. Adult behavioral measures showed expected sex-dependent differences, that did not differ between 2-CP and saline groups. Single maximum tolerated in vivo doses of intrathecal 2-CP produced reversible spinal anesthesia in juvenile rodents without detectable evidence of developmental neurotoxicity. Current results cannot be extrapolated to repeated dosing or prolonged infusion

Delivering Parenting Interventions through Health Services in the Caribbean

Integrating early childhood interventions with health and nutrition services has been recommended, however there is limited information on interventions that are effective and feasible for delivery through health services. In this trial we developed and evaluated a parenting program that could be integrated into primary health center visits