Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations.

Per- and polyfluoroalkyl substances (PFAS) are present in water and >99% of human serum. They are found in brains of wildlife; however, little is known about effects on the developing brain. To determine the effects of PFAS on brain and cardiac innervation, we conducted an outdoor mesocosm experiment with Northern leopard frog larvae (Rana pipiens) exposed to control, 10 ppb perfluorooctane sulfonate (PFOS), or a PFAS mixture totaling 10 ppb that mimicked aqueous film forming foam-impacted surface water (4 ppb PFOS, 3 ppb perfluorohexane sulfonate, 1.25 ppb perfluorooctanoate, 1.25 ppb perfluorohexanoate, and 0.5 ppb perfluoro-n-pentanoate). Water was spiked with PFAS and 25 larvae (Gosner stage (GS) 25) added to each mesocosm (n = 4 mesocosms per treatment). After 30 days, we harvested eight brains per mesocosm and remaining larvae developed to GS 46 (i.e. metamorphosis) before brains and hearts were collected. Weight, length, GS, and time to metamorphosis were recorded. Brain concentrations of all five PFAS were quantified using LC/MS/MS. Dopamine and metabolites, serotonin and its metabolite, norepinephrine, γ-aminobutyric acid, and glutamate were quantified using High Performance Liquid Chromatography with electrochemical detection while acetylcholine and acetylcholinesterase activity were quantified with the Invitrogen Amplex Red Acetylcholine Assay. PFOS accumulated in the brain time- and dose-dependently. After 30 days, the mixture decreased serotonin while both PFAS treatments decreased glutamate. Interestingly, acetylcholine increased in PFAS treatments at GS 46. This research shows that developmental environmentally relevant exposure to PFAS changes neurotransmitters, especially acetylcholine.

The cost of cerebral ischaemia.

Cerebral ischaemia is a major cause of disability and death globally and has a profoundly negative impact on the individuals it affects, those that care for them and society as a whole. The most common and familiar manifestation is stroke, 85% of which are ischaemic and which is the second leading cause of death and most common cause of complex chronic disability worldwide. Stroke survivors often suffer from long-term neurological disabilities significantly reducing their ability to integrate effectively in society with all the financial and social consequences that this implies. These difficulties cascade to their next of kin who often become caregivers and are thus indirectly burdened. A more insidious consequence of cerebral ischaemia is progressive cognitive impairment causing dementia which although less abrupt is also associated with a significant long-term disability. Globally cerebrovascular diseases are responsible for 5.4 million deaths every year (1 in 10 of total). Approximately 3% of total healthcare expenditure is attributable to cerebral ischaemia with cerebrovascular diseases costing EU healthcare systems 21 billion euro in 2003. The cost to the wider economy (including informal care and lost productivity) is even greater with stroke costing the UK 7-8 billion pound in 2005 and the US $62.7 billion in 2007. Cerebrovascular disease cost the EU 34 billion euro in 2003. From 2005 to 2050 the anticipated cost of stroke to the US economy is estimated at $2.2 trillion. Given the global scale of the problem and the enormous associated costs it is clear that there is an urgent need for advances in the prevention of cerebral ischaemia and its consequences. Such developments would result in profound benefits for both individuals and their wider societies and address one of the world's most pre-eminent public health issues.

A compact linac for intensity modulated proton therapy based on a dielectric wall accelerator.

A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) system is described. The system is being designed to deliver fast IMPT so that larger target volumes and motion management can be accomplished. The system will be ideal for large and complex target volumes in young patients. The basis of the design is the dielectric wall accelerator (DWA) system being developed at the Lawrence Livermore National Laboratory (LLNL). The DWA uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. High electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The system will produce individual pulses that can be varied in intensity, energy and spot width. The IMPT planning system will optimize delivery characteristics. The system will be capable of being sited in a conventional linac vault and provide intensity modulated rotational therapy. Feasibility tests of an optimization system for selecting the position, energy, intensity and spot size for a collection of spots comprising the treatment are underway. A prototype is being designed and concept designs of the envelope and environmental needs of the unit are beginning. The status of the developmental new technologies that make the compact system possible will be reviewed. These include, high gradient vacuum insulators, solid dielectric materials, SiC photoconductive switches and compact proton sources.

Mortality and vascular outcomes in patients treated for thyroid dysfunction.

CONTEXT: There are limited studies describing mortality and morbidity in patients treated for hyperthyroidism, and no data exist for people with treated hypothyroidism. OBJECTIVE: The objective of the study was to describe all-cause mortality and vascular mortality and morbidity in patients after treatment for hyperthyroidism and hypothyroidism. DESIGN: This was a population-based cohort study from 1994 to 2001. SETTING: The study was conducted in Tayside, Scotland. PATIENTS: All patients were treated for thyroid dysfunction. INTERVENTION(S): Event rates among patients with thyroid dysfunction were compared with rates in the general population. We measured standardized mortality ratio and standardized incidence ratio (SIR). MAIN OUTCOME MEASURE(S): The primary outcome was all-cause mortality. The secondary outcome was serious vascular event, the composite end point of nonfatal myocardial infarction, nonfatal stroke, or vascular death. RESULTS: There were 15,889 primary hypothyroid and 3,888 hyperthyroid patients. There were 3,116,719 patient-years of follow-up in 524,152 subjects in the general population. No increase was found in all-cause mortality or serious vascular events in patients with treated hypothyroidism or hyperthyroidism. Nonfatal ischemic heart disease [SIR 1.23, 95% confidence interval (CI) 1.10-1.36] and dysrhythmias (SIR 1.32, 95% CI 1.11-1.57) were increased in treated hypothyroidism when adjusted for age, sex, diabetic status, and previous vascular disease. In treated stabilized hyperthyroidism, only the risk of dysrhythmias was increased (SIR 2.71, 95% CI 1.63-4.24). Risk of heart failure or cerebrovascular disease was not increased in either patient group. CONCLUSIONS: We found no increase in all-cause mortality in subjects with treated thyroid disease. However, there was increased risk of cardiovascular morbidity in patients with treated primary hypothyroidism and dysrhythmias in treated hyperthyroidism.

Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia.

Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron-emission tomography in eight patients with schizophrenia who were not receiving medication and in six age-matched normal volunteers. Subjects sat in an acoustically treated, darkened room with eyes closed after injection of 3 to 5 mCi of deoxyglucose 18F. After uptake, seven to eight horizontal brain scans parallel to the canthomeatal line were done. Scans were treated digitally, with a 2.3-cm strip peeled off each slice and ratios to whole-slice activity computed. Patients with schizophrenia showed lower ratios in the frontal cortex, indicating relatively lower glucose use than normal control subjects; this was consistent with previously reported studies of regional cerebral blood flow. Patients also showed diminished ratios for a 2.3-cm square that was positioned over central gray-matter areas on the left but not on the right side. These findings are preliminary; issues of control of mental activity, brain structure identification, and biologic and anatomic heterogeneity of schizophrenia remain to be explored.

The thyroid epidemiology, audit, and research study: thyroid dysfunction in the general population.

The objective of this study was to define the level of treated thyroid dysfunction in a complete and representative population base in an area of sufficient dietary iodine intake. We used record-linkage technology to retrospectively identify subjects treated for hyperthyroidism or hypothyroidism in the general population of Tayside, Scotland from 1 January 1993 to 30 April 1997. Thyroid status was ascertained by record linkage of patient-level datasets containing details of treatments for hyperthyroidism and hypothyroidism. We identified 620 incident cases of hyperthyroidism, an incidence rate of 0.77/1000 x yr [95% confidence interval (CI), 0.70-0.84] in females and 0.14/1000 x yr (95% CI, 0.12-0.18) in males. There were 3,486 incident cases of diagnosed primary hypothyroidism, an incidence rate of 4.98/1000 x yr (95% CI, 4.81-5.17) in females and 0.88/1000 x yr (95% CI, 0.80-0.96) in males. For both hyperthyroidism and hypothyroidism, the incidence increased with age, and females were affected two to eight times more than males across the age range. The midyear point prevalence of all-cause hypothyroidism rose from 2.2% in 1993 to 3.0% in 1996. The level of thyroid dysfunction in Tayside, Scotland is higher than previously reported, and it increased from 1993 to 1996.

Annual and seasonal changes in diets of martens: evidence from stable isotope analysis.

Theory predicts that generalist predators will switch to alternative prey when preferred foods are not readily available. Studies on the feeding ecology of the American marten (Martes americana) throughout North America suggest that this mustelid is a generalist predator feeding largely on voles (Microtus sp.; Clethrionomys sp.). We investigated seasonal and annual changes in diets of martens in response to the changing abundance of small rodents (Peromyscus keeni, and Microtus longicaudus) on Chichagof Island, Southeast Alaska, using stable isotope analysis. We hypothesized that martens would feed primarily on small rodents during years with high abundance of these prey species, whereas during years of low abundance of prey, martens would switch to feed primarily on the seasonally available carcasses of salmon. We also hypothesized that home-range location on the landscape (i.e., access to salmon streams) would determine the type of food consumed by martens, and martens feeding on preferred prey would exhibit better body condition than those feeding on other foods. We live-captured 75 martens repeatedly, from mid-February to mid-December 1992-1994. We also obtained marten carcasses from trappers during late autumn 1991 and 1992, from which we randomly sub-sampled 165 individuals. Using stable isotope ratios and a multiple-source mixing model, we inferred that salmon carcasses composed a large portion of the diet of martens in autumn during years of low abundance of rodents (1991 and 1992). When small rodents were available in high numbers (1993 and 1994), they composed the bulk of the diet of martens in autumn, despite salmon carcasses being equally available in all years. Selection for small rodents occurred only in seasons in which abundance of small rodents was low. Logistic regression revealed that individuals with access to salmon streams were more likely to incorporate salmon carcasses in their diet during years of low abundance of small rodents. Using stable isotope analysis on repeated samples from the same individuals, we explored some of the factors underlying feeding habits of individuals under variable ecological conditions. We were unable to demonstrate that body weights of live-captured male and female martens differed significantly between individuals feeding on marine-derived or terrestrial diets. Therefore, martens, as true generalist predators, switched to alternative prey when their principal food was not readily available on a seasonal or annual basis. Although salmon carcasses were not a preferred food for martens, they provided a suitable alternative to maintain body condition during years when small rodents were not readily available.

Patient choice of primary care practitioner for orofacial symptoms.

OBJECTIVE: To determine patients' preferences regarding consultation of medical or dental practitioners for various orofacial symptoms, including patients' perceptions of practitioners' training and ability to diagnose and treat these symptoms. METHOD: Patients attending oral and maxillofacial clinics in Dumfries & Galloway, Scotland in relation to a variety of complaints were invited to complete a questionnaire. RESULTS: From a sample size of 254 patients, 220 correctly completed questionnaires were received. This showed 69% of patients regarded medical practitioners as being better trained to diagnose and treat non-dental orofacial symptoms. Eighty percent of patients regarded medical practitioners as being more accessible when booking an appointment. Seventy-eight percent of patients did not regard charges for dental care as being an important factor when deciding which practitioner they should consult. CONCLUSION: Despite the significant differences between medical and dental practitioners in undergraduate and postgraduate training in orofacial disease, most patients would choose to visit a medical rather than dental practitioner. While these results suggest the need for postgraduate educational support for medical practitioners in treating orofacial pain and oral mucosal disease, they also imply a need for change in the concept of provision of oral healthcare by general dental practitioners.