Temporal Patterns in Perchlorate, Thiocyanate, and Iodide Excretion in Human Milk

BACKGROUND: Perchlorate and thiocyanate interfere with iodide uptake at the sodium–iodide symporter and are potential disruptors of thyroid hormone synthesis. Perchlorate is a common contaminant of water, food, and human milk. Although it is known that iodide undergoes significant diurnal variations in serum and urinary excretion, less is known about diurnal variations of milk iodide levels. OBJECTIVES: Variability in perchlorate and thiocyanate excretion in human milk has not been examined. Our objective was to determine variability of perchlorate, thiocyanate, and iodide in serially collected samples of human milk. METHODS: Ten lactating women were asked to collect six milk samples on each of 3 days. As an alternative, subjects were asked to collect as many milk samples as comfortably possible over 3 days. Samples were analyzed for perchlorate, iodide, and thiocyanate by ion chromatography coupled with mass spectrometry. RESULTS: Individual perchlorate, iodide, and thiocyanate levels varied significantly over time; there was also considerable variation among individuals. The iodide range, mean ± SD, and median for all samples (n = 108) were 3.1–334 μg/L, 87.9 ± 80.9 μg/L, and 55.2 μg/L, respectively. The range, mean ± SD, and median of perchlorate in all samples (n = 147) were 0.5–39.5 μg/L, 5.8 ± 6.2 μg/L, and 4.0 μg/L. The range, mean ± SD, and median of thiocyanate in all samples (n = 117) were 0.4 –228.3 μg/L, 35.6 ± 57.9 μg/L, and 5.6 μg/L. The data are not symmetrically distributed; the mean is higher than the median in all cases. CONCLUSIONS: Iodine intake may be inadequate in a significant fraction of this study population. Perchlorate and thiocyanate appear to be common in human milk. The role of these chemicals in reducing breast milk iodide is in need of further investigation

A novel application of capnography during controlled human exposure to air pollution

BACKGROUND: The objective was to determine the repeatability and stability of capnography interfaced with human exposure facility. METHODS: Capnographic wave signals were obtained from five healthy volunteers exposed to particle-free, filtered air during two consecutive 5 min intervals, 10 min apart, within the open and then the sealed and operational human exposure facility (HEF). Using a customized setup comprised of the Oridion Microcap(® )portable capnograph, DA converter and AD card, the signal was acquired and saved as an ASCII file for subsequent processing. The minute ventilation (VE), respiratory rate (RR) and expiratory tidal volume (V(TE)) were recorded before and after capnographic recording and then averaged. Each capnographic tracing was analyzed for acceptable waves. From each recorded interval, 8 to 19 acceptable waves were selected and measured. The following wave parameters were obtained: total length and length of phase II and III, slope of phase II and III, area under the curve and area under phase III. In addition, we recorded signal measures including the mean, standard deviation, mode, minimum, maximum – which equals end-tidal CO(2 )(EtCO(2)), zero-corrected maximum and true RMS. RESULTS: Statistical analysis using a paired t-test for means showed no statistically significant changes of any wave parameters and wave signal measures, corrected for RR and V(TE), comparing the measures when the HEF was open vs. sealed and operational. The coefficients of variation of the zero-corrected and uncorrected EtCO(2), phase II absolute difference, signal mean, standard deviation and RMS were less than 10% despite a sub-atmospheric barometric pressure, and slightly higher temperature and relative humidity within the HEF when operational. CONCLUSION: We showed that a customized setup for the acquisition and processing of the capnographic wave signal, interfaced with HEF was stable and repeatable. Thus, we expect that analysis of capnographic waves in controlled human air pollution exposure studies is a feasible tool for characterization of cardio-pulmonary effects of such exposures

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Patient-centred measurement in ophthalmology – a paradigm shift

Ophthalmologists and researchers in ophthalmology understand what a rapidly evolving field ophthalmology is, and that to conduct good research it is essential to use the latest and best methods. In outcomes research, one modern initiative has been to conduct holistic measurement of outcomes inclusive of the patient's point of view; patient-centred outcome. This, of course, means including a questionnaire. However, the irony of trying to improve outcomes research by being inclusive of many measures is that the researcher may not be expert in all measures used. Certainly, few people conducting outcomes research in ophthalmology would claim to be questionnaire experts. Most tend to be experts in their ophthalmic subspecialty and probably simply choose a popular questionnaire that appears to fit their needs and think little more about it. Perhaps, unlike our own field, we assume that the field of questionnaire research is relatively stable. This is far from the case. The measurement of patient-centred outcomes with questionnaires is a rapidly evolving field. Indeed, over the last few years a paradigm shift has occurred in patient-centred measurement

Methicillin sensitive Staphylococcus aureus producing Panton-Valentine leukocidin toxin in Trinidad & Tobago: a case report

<p>Abstract</p> <p>Introduction</p> <p>Certain <it>Staphylococcus aureus </it>strains produce Panton-Valentine leukocidin, a toxin that lyses white blood cells causing extensive tissue necrosis and chronic, recurrent or severe infection. This report documents a confirmed case of methicillin-sensitive <it>Staphylococcus aureus </it>strain harboring Panton-Valentine leukocidin genes from Trinidad and Tobago. To the best of our knowledge, this is the first time that such a case has been identified and reported from this country.</p> <p>Case presentation</p> <p>A 13-year-old Trinidadian boy of African descent presented with upper respiratory symptoms and gastroenteritis-like syptoms. About two weeks later he was re-admitted to our hospital complaining of pain and weakness affecting his left leg, where he had received an intramuscular injection of an anti-emetic drug. He deteriorated and developed septic arthritis, necrotizing fasciitis and septic shock with acute respiratory distress syndrome, leading to death within 48 hours of admission despite intensive care treatment. The infection was caused by <it>S. aureus</it>. Bacterial isolates from specimens recovered from our patient before and after his death were analyzed using microarray DNA analysis and <it>spa </it>typing, and the results revealed that the <it>S. aureus </it>isolates belonged to clonal complex 8, were methicillin-susceptible and positive for Panton-Valentine leukocidin. An autopsy revealed multi-organ failure and histological tissue stains of several organs were also performed and showed involvement of his lungs, liver, kidneys and thymus, which showed Hassal's corpuscles.</p> <p>Conclusion</p> <p>Rapid identification of Panton-Valentine leukocidin in methicillin-sensitive <it>S. aureus </it>isolates causing severe infections is necessary so as not to miss their potentially devastating consequences. Early feedback from the clinical laboratories is crucial.</p

Methicillin sensitive Staphylococcus aureus producing Panton-Valentine leukocidin toxin in Trinidad & Tobago: a case report

<p>Abstract</p> <p>Introduction</p> <p>Certain <it>Staphylococcus aureus </it>strains produce Panton-Valentine leukocidin, a toxin that lyses white blood cells causing extensive tissue necrosis and chronic, recurrent or severe infection. This report documents a confirmed case of methicillin-sensitive <it>Staphylococcus aureus </it>strain harboring Panton-Valentine leukocidin genes from Trinidad and Tobago. To the best of our knowledge, this is the first time that such a case has been identified and reported from this country.</p> <p>Case presentation</p> <p>A 13-year-old Trinidadian boy of African descent presented with upper respiratory symptoms and gastroenteritis-like syptoms. About two weeks later he was re-admitted to our hospital complaining of pain and weakness affecting his left leg, where he had received an intramuscular injection of an anti-emetic drug. He deteriorated and developed septic arthritis, necrotizing fasciitis and septic shock with acute respiratory distress syndrome, leading to death within 48 hours of admission despite intensive care treatment. The infection was caused by <it>S. aureus</it>. Bacterial isolates from specimens recovered from our patient before and after his death were analyzed using microarray DNA analysis and <it>spa </it>typing, and the results revealed that the <it>S. aureus </it>isolates belonged to clonal complex 8, were methicillin-susceptible and positive for Panton-Valentine leukocidin. An autopsy revealed multi-organ failure and histological tissue stains of several organs were also performed and showed involvement of his lungs, liver, kidneys and thymus, which showed Hassal's corpuscles.</p> <p>Conclusion</p> <p>Rapid identification of Panton-Valentine leukocidin in methicillin-sensitive <it>S. aureus </it>isolates causing severe infections is necessary so as not to miss their potentially devastating consequences. Early feedback from the clinical laboratories is crucial.</p

An organizing framework for informal caregiver interventions: detailing caregiving activities and caregiver and care recipient outcomes to optimize evaluation efforts

Abstract Background Caregiver interventions may help improve the quality of informal care. Yet the lack of a systematic framework specifying the targets and outcomes of caregiver interventions hampers our ability to understand what has been studied, to evaluate existing programs, and to inform the design of future programs. Our goal was to develop an organizing framework detailing the components of the caregiving activities and the caregiver and care recipient outcomes that should be affected by an intervention. In so doing, we characterize what has been measured in the published literature to date and what should be measured in future studies to enable comparisons across interventions and across time. Methods Our data set comprises 121 reports of caregiver interventions conducted in the United States and published between 2000 and 2009. We extracted information on variables that have been examined as primary and secondary outcomes. These variables were grouped into categories, which then informed the organizing framework. We calculated the frequency with which the interventions examined each framework component to identify areas about which we have the most knowledge and under-studied areas that deserve attention in future research. Results The framework stipulates that caregiver interventions seek to change caregiving activities, which in turn affect caregiver and care recipient outcomes. The most frequently assessed variables have been caregiver psychological outcomes (especially depression and burden) and care recipient physical and health care use outcomes. Conclusions Based on the organizing framework, we make three key recommendations to guide interventions and inform research and policy. First, all intervention studies should assess quality and/or quantity of caregiving activities to help understand to what extent and how well the intervention worked. Second, intervention studies should assess a broad range of caregiver and care recipient outcomes, including considering whether expanding to economic status and health care use of the caregiver can be accommodated, to ease subsequent economic evaluations of caregiving. Third, intervention studies should measure a common set of outcomes to facilitate cross-time and cross-study comparisons of effectiveness

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation