The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial

Objective: To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development. Methods: A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions) versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions) in inactive, overweight/obese (25.0-34.9 kg/m2) males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance HOMA). Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value. Results: Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80); 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control) was observed for waist circumference (-4.5 95%CI -7.5, -1.4 cm; p < 0.01). Effects on primary outcomes were not statistically significant. Conclusion: This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this population and relax inclusion criteria to maximize recruitment. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000401257. © 2015 Winzer et al

Geophagy Practices and the Content of Chemical Elements in the Soil Eaten by Pregnant Women in Artisanal and Small Scale Gold Mining Communities in Tanzania.

Geophagy, a form of pica, is the deliberate consumption of soil and is relatively common across Sub-Saharan Africa. In Tanzania, pregnant women commonly eat soil sticks sold in the market (pemba), soil from walls of houses, termite mounds, and ground soil (kichuguu). The present study examined geophagy practices of pregnant women in a gold mining area of Geita District in northwestern Tanzania, and also examined the potential for exposure to chemical elements by testing soil samples. We conducted a cross sectional study using a convenience sample of 340 pregnant women, ranging in age from 15-49 years, who attended six government antenatal clinics in the Geita District, Tanzania. Structured interviews were conducted in June-August, 2012, to understand geophagy practices. In addition, soil samples taken from sources identified by pregnant women practicing geophagy were analysed for mineral element content. Geophagy was reported by 155 (45.6%) pregnant women with 85 (54.8%) initiating the practice in the first trimester. A total of 101 (65%) pregnant women reported eating soil 2 to 3 times per day while 20 (13%) ate soil more than 3 times per day. Of 155 pregnant women 107 (69%) bought pemba from local shops, while 48 (31%) consumed ground soil kichuguu. The estimated mean quantity of soil consumed from pemba was 62.5 grams/day. Arsenic, chromium, copper, iron, manganese, nickel and zinc levels were found in both pemba and kichuguu samples. Cadmium and mercury were found only in the kichuguu samples. Based on daily intake estimates, arsenic, copper and manganese for kichuguu and copper and manganese for pemba samples exceed the oral Minimum Risk Levels designated by the U.S. Agency for Toxic Substance and Disease Registry. Almost 50% of participants practiced geophagy in Geita District consistent with other reports from Africa. Both pemba and kichuguu contained chemical elements at varying concentration, mostly above MRLs. As such, pregnant women who eat soil in Geita District are exposed to potentially high levels of chemical elements, depending upon frequency of consumption, daily amount consumed and the source location of soil eaten

Stochastic Ion Channel Gating in Dendritic Neurons: Morphology Dependence and Probabilistic Synaptic Activation of Dendritic Spikes

Neuronal activity is mediated through changes in the probability of stochastic transitions between open and closed states of ion channels. While differences in morphology define neuronal cell types and may underlie neurological disorders, very little is known about influences of stochastic ion channel gating in neurons with complex morphology. We introduce and validate new computational tools that enable efficient generation and simulation of models containing stochastic ion channels distributed across dendritic and axonal membranes. Comparison of five morphologically distinct neuronal cell types reveals that when all simulated neurons contain identical densities of stochastic ion channels, the amplitude of stochastic membrane potential fluctuations differs between cell types and depends on sub-cellular location. For typical neurons, the amplitude of membrane potential fluctuations depends on channel kinetics as well as open probability. Using a detailed model of a hippocampal CA1 pyramidal neuron, we show that when intrinsic ion channels gate stochastically, the probability of initiation of dendritic or somatic spikes by dendritic synaptic input varies continuously between zero and one, whereas when ion channels gate deterministically, the probability is either zero or one. At physiological firing rates, stochastic gating of dendritic ion channels almost completely accounts for probabilistic somatic and dendritic spikes generated by the fully stochastic model. These results suggest that the consequences of stochastic ion channel gating differ globally between neuronal cell-types and locally between neuronal compartments. Whereas dendritic neurons are often assumed to behave deterministically, our simulations suggest that a direct consequence of stochastic gating of intrinsic ion channels is that spike output may instead be a probabilistic function of patterns of synaptic input to dendrites