Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

Dance improves symptoms, functional mobility and fine manual dexterity in people with Parkinson disease: a quasi-experimental controlled efficacy study.

BACKGROUND: Clinically, individuals diagnosed with Parkinson disease (PD) present several symptoms that impact on their functional independence and quality of life. While there is accumulating evidence supporting dance as an effective symptom management option, few studies have objectively assessed these benefits, particularly related to the Dance for Parkinson's Disease® (DfPD®) program. AIM: The aim of this study was to explore the effects of DfPD®-based dance classes on disease-related symptoms, fine-manual dexterity and functional mobility in people with PD. DESIGN: A quasi-experimental controlled efficacy study, with pre and post testing of two parallel groups (dance versus control). SETTING: Community. POPULATION: Thirty-three participants with PD allocated to one of two groups: dance group (DG; N.=17; age=65.8±11.7 years) or control group (CG: N.=16; age=67.0±7.7 years). They were cognitively intact (Addenbrooke's Score: DG=93.2±3.6, CG=92.6±4.3) and in early-stage of disease (Hoehn & Yahr: DG=1.6±0.7, CG=1.5±0.8). METHODS: The DG undertook a one-hour DfPD®-based class, twice weekly for 12 weeks. The CG had treatment as usual. Both groups were assessed at baseline and after 12 weeks on disease-related symptom severity (MDS-Unified Parkinson Disease Rating Scale: MDS-UPDRS), fine-manual dexterity (Perdue Peg Board), measures of functional mobility (Timed Up & Go: single & dual task, Tinetti, Berg, Mini-BESTest) and self-rated balance and gait questionnaires (Activities Balance Confidence Scale: ABC-S; Gait and Falls: G&F-Q; Freezing of Gait: FOG). RESULTS: Compared to the CG, there was significantly greater improvement in the DG pre-post change scores on measures of symptom severity MDS-UPDRS, dexterity, six measures of functional mobility, and the ABC-S, G&F-Q, FOG questionnaires. CONCLUSIONS: DfPD®-based dance classes improved disease-related symptom severity, fine-manual dexterity, and functional mobility. Feasibility of the approach for a large scale RCT was also confirmed. CLINICAL REHABILITATION IMPACT: DfPD® could be an effective supportive therapy for the management of symptoms and functional abilities in PD.

Narrow pollen diets are associated with declining Midwestern bumble bee species.

Many species of bumble bee (Bombus) have declined in range and abundance across Europe, the Americas, and Asia, whereas other species have persisted and remain common and widespread. One explanation as to why some species have declined, based primarily on studies of the European bumble bee fauna, is that declining species have relatively narrow pollen-foraging niches and are less able to use alternative host plants in the absence of their preferred hosts. Though extensively explored in Europe, this hypothesis has not been investigated in North America, in part due to incomplete information on the foraging niche of many species. We selected 12 bumble bee species found in Michigan and quantified their pollen diets using museum specimens. We also extensively resurveyed the state to understand their contemporary status and distribution. Compared to a pre-2000 baseline, six species remain relatively common and widespread, whereas six species show range contractions of over 50%. There was a significant relationship between dietary breadth and distributional range change, with declined or declining species collecting around one-third fewer pollen types than stable species. Though there were significant compositional differences, we found no differences in the number of pollen types collected by species with differing tongue lengths. Overall, these results support the hypothesis that species with narrower dietary niches are at greater risk of decline. However, it is not clear if narrow dietary niches are a cause of declines, or if both are driven by an underlying factor such as proximity to the edge of climatic niches. Further research is needed to improve our understanding of dietary niche in bumble bees, and how it interacts with other factors to influence population trajectories of stable and at-risk species.

Could Heat Therapy Be an Effective Treatment for Alzheimer's and Parkinson's Diseases? A Narrative Review.

Neurodegenerative diseases involve the progressive deterioration of structures within the central nervous system responsible for motor control, cognition, and autonomic function. Alzheimer's disease and Parkinson's disease are among the most common neurodegenerative disease and have an increasing prevalence over the age of 50. Central in the pathophysiology of these neurodegenerative diseases is the loss of protein homeostasis, resulting in misfolding and aggregation of damaged proteins. An element of the protein homeostasis network that prevents the dysregulation associated with neurodegeneration is the role of molecular chaperones. Heat shock proteins (HSPs) are chaperones that regulate the aggregation and disaggregation of proteins in intracellular and extracellular spaces, and evidence supports their protective effect against protein aggregation common to neurodegenerative diseases. Consequently, upregulation of HSPs, such as HSP70, may be a target for therapeutic intervention for protection against neurodegeneration. A novel therapeutic intervention to increase the expression of HSP may be found in heat therapy and/or heat acclimation. In healthy populations, these interventions have been shown to increase HSP expression. Elevated HSP may have central therapeutic effects, preventing or reducing the toxicity of protein aggregation, and/or peripherally by enhancing neuromuscular function. Broader physiological responses to heat therapy have also been identified and include improvements in muscle function, cerebral blood flow, and markers of metabolic health. These outcomes may also have a significant benefit for people with neurodegenerative disease. While there is limited research into body warming in patient populations, regular passive heating (sauna bathing) has been associated with a reduced risk of developing neurodegenerative disease. Therefore, the emerging evidence is compelling and warrants further investigation of the potential benefits of heat acclimation and passive heat therapy for sufferers of neurodegenerative diseases.

Pectin extraction from pomegranate peels with citric acid.

Pectins were extracted from pomegranate peels with citric acid, according to a central composite design with three variables: pH (2-4), temperature (70-90°C), and extraction time (40-150min). Fourier transform infrared (FTIR) spectroscopy was used to follow changes in material composition during the main steps of pectin extraction, and also to determine the degree of methyl esterification and galacturonic acid content of pectins produced under different conditions. Harsh conditions enhanced the extraction yield and the galacturonic acid contents, but decreased the degree of methoxylation. The optimum extraction conditions, defined as those predicted to result in a yield of galacturonic acid higher than 8g/100g while keeping a minimum degree of methoxylation of 54% were: 88°C, 120min, pH 2.5. Close agreement was found between experimental and predicted values at the extraction conditions defined as optimum.

Pomegranate peel pectin films as affected by montmorillonite.

The industrial production of pomegranate juice has been favored by its alleged health benefits derived from its antioxidant properties. The processing of pomegranate juice involves squeezing juice from the fruit with the seeds and the peels together, leaving a pomace consisting of approximately 73 wt% peels. In this study, pectin was extracted from pomegranate peels, and used to produce films with different contents of montmorillonite (MMT) as a nanoreinforcement material. The nanoreinforcement improved the tensile strength and modulus of films when added at up to 6 wt%, while the further addition of MMT (to 8 wt%) reduced the reinforcement effect, probably because of dispersion problems. The elongation was decreased with increasing MMT concentrations. The water vapor permeability decreased with increasing MMT contents up to 8 wt% MMT, indicating that the increased tortuosity of the permeant path was effective on barrier properties of the film.

Optimization of pectin extraction from banana peels with citric acid by using response surface methodology.

A central composite design was used to determine effects of pH (2.0-4.5), extraction temperature (70-90 °C) and time (120-240 min) on the yield, degree of methoxylation (DM) and galacturonic acid content (GA) of pectins extracted from banana peels with citric acid. Changes in composition during the main steps of pectin extraction were followed by Fourier transform infrared (FTIR) spectroscopy. FTIR was also used to determine DM and GA of pectins. Harsh temperature and pH conditions enhanced the extraction yield, but decreased DM. GA presented a maximum value at 83 °C, 190 min, and pH 2.7. The yield of galacturonic acid (YGA), which took into account both the extraction yield and the pectin purity, was improved by higher temperature and lower pH values. The optimum extraction conditions, defined as those resulting in a maximum YGA while keeping DM at a minimum of 51%, were: 87 °C, 160 min, pH 2.0.

Relationship of low vitamin D status with positive, negative and cognitive symptom domains in people with first-episode schizophrenia.

AIM: Deficient vitamin D levels are very common among Americans of all ages and ethnicities, but little is known about its prevalence or associated problems among those with schizophrenia. METHODS: Stored plasma from 20 recent onset schizophrenia subjects and 20 matched healthy comparison subjects were analysed for 25 OH vitamin D, and related to measures of symptom severity and neurocognition. RESULTS: There was no significant difference in mean 25 OH vitamin D between the schizophrenia and the healthy comparison subjects (28.2 standard deviation (SD) 12.6 ng mL(-1) vs. 29.9 SD 14.3 ng mL(-1) ), and about half the subjects in each group had insufficient levels (<30 ng mL(-1) ). Among psychosis subjects, greater severity of negative symptoms was correlated with lower vitamin D status (r = -0.55, P = 0.012); the correlations of overall symptom severity and positive symptom severity with 25 OH vitamin D levels approached significance (r = -0.42, P = 0.07 and r = -0.36, P = 0.12, respectively). There was no relationship of vitamin D with depressive symptoms. Among the schizophrenia subjects, lower 25 OH vitamin D levels were associated with more severe overall cognitive deficits (r = 0.56, P = 0.019). CONCLUSION: This study found that lower vitamin D levels in schizophrenia subjects were associated with more severe negative symptoms and overall cognitive deficits. However, the cross-sectional design precludes any conclusions about whether low vitamin D status in fact causes more severe negative symptoms and cognitive impairments. No relationship was found between lower vitamin D levels and depressive symptoms.

Intraoperative parathyroid hormone concentration to confirm removal of hypersecretory parathyroid tissue and time to postoperative normocalcaemia in nine dogs with primary hyperparathyroidism.

OBJECTIVE: To determine (1) whether the intraoperative parathyroid hormone concentration ([PTH]) during parathyroidectomy (PTX) can be used to indicate cure in dogs with primary hyperparathyroidism and (2) the time taken for postoperative serum calcium concentration to normalise. DESIGN: Retrospective study (2005-10) from a private referral hospital in Sydney, New South Wales, Australia. PROCEDURE: Nine client-owned dogs underwent surgical PTX for naturally occurring primary hyperparathyroidism. [PTH] was measured from serum samples taken immediately post-induction (pre-PTX]) and at least 20 min after adenoma removal (post-PTX) for all dogs, and during parathyroid gland manipulation (intra-PTX) for six dogs. The concentration of ionised calcium (iCa) was measured at various time points postoperatively until it normalised, then stabilised or decreased below reference ranges. Statistical analysis compared the mean pre-, intra- and post-PTX [PTH] and the average rate of decline of iCa concentration postoperatively. RESULTS: All dogs demonstrated a significant decrease from mean pre-PTX [PTH] (168.51 pg/mL) to mean post-PTX [PTH] (29.20 pg/mL). There was a significant increase in mean intra-PTX [PTH] (279.78 pg/mL). The average rate of decline of iCa concentration postoperatively to within the reference range (1.12-1.40 mmol/L) occurred after 24 h. CONCLUSION: Intraoperative measurements of [PTH] can be used clinically to determine cure of primary hyperparathyroidism. Parathyroid hormone increases significantly during parathyroid gland manipulation. Plasma iCa concentration returns to within the reference range on average 24 h after successful PTX. Not all dogs require vitamin D or calcium supplementation pre- or postoperatively.

Neuregulin-1 genotype is associated with structural differences in the normal human brain.

The human neuregulin-1 (NRG-1) gene is highly expressed in the brain, is implicated in numerous functions associated with neuronal development, and is a leading candidate gene for schizophrenia. The T allele of SNP8NRG243177, part of a risk haplotype for schizophrenia, has been previously associated with decreases in white matter in the right anterior internal capsule and the left anterior thalamic radiation. To our knowledge no studies have described the effects of SNP8NRG243177 on grey matter volume at a voxelwise level. We assessed associations between this SNP and brain structure in 79 general population volunteers from the Northern Finland 1966 Birth Cohort (NFBC 1966). We show, for the first time, that genetic variation in SNP8NRG243177 is associated with variation in frontal brain structure in both grey and white matter. T allele carriers showed decreased grey matter volume in several frontal gyri, including inferior, middle and superior frontal gyri and the anterior cingulate gyrus, as well as decreased white matter volume in the regions of the genu and body of the corpus callosum, anterior and superior corona radiata, anterior limb of the internal capsule and external capsule regions traversed by major white matter tracts of the anterior thalamic radiation, and the inferior fronto-occipital fasciculus. These results suggest that this genetic variant may mediate risk for schizophrenia, in part, through its effect on brain structure in these regions.

Agronomic phosphorus imbalances across the world's croplands.

Increased phosphorus (P) fertilizer use and livestock production has fundamentally altered the global P cycle. We calculated spatially explicit P balances for cropland soils at 0.5° resolution based on the principal agronomic P inputs and outputs associated with production of 123 crops globally for the year 2000. Although agronomic inputs of P fertilizer (14.2 Tg of P·y(-1)) and manure (9.6 Tg of P·y(-1)) collectively exceeded P removal by harvested crops (12.3 Tg of P·y(-1)) at the global scale, P deficits covered almost 30% of the global cropland area. There was massive variation in the magnitudes of these P imbalances across most regions, particularly Europe and South America. High P fertilizer application relative to crop P use resulted in a greater proportion of the intense P surpluses (>13 kg of P·ha(-1)·y(-1)) globally than manure P application. High P fertilizer application was also typically associated with areas of relatively low P-use efficiency. Although manure was an important driver of P surpluses in some locations with high livestock densities, P deficits were common in areas producing forage crops used as livestock feed. Resolving agronomic P imbalances may be possible with more efficient use of P fertilizers and more effective recycling of manure P. Such reforms are needed to increase global agricultural productivity while maintaining or improving freshwater quality.

Land-use legacies are important determinants of lake eutrophication in the anthropocene.

BACKGROUND: A hallmark of the latter half of the 20(th) century is the widespread, rapid intensification of a variety of anthropogenically-driven environmental changes--a "Great Acceleration." While there is evidence of a Great Acceleration in a variety of factors known to be linked to water quality degradation, such as conversion of land to agriculture and intensification of fertilizer use, it is not known whether there has been a similar acceleration of freshwater eutrophication. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative reconstructions of diatom-inferred total phosphorus (DI-TP) as a proxy for lake trophic state, we synthesized results from 67 paleolimnological studies from across Europe and North America to evaluate whether most lakes showed a pattern of eutrophication with time and whether this trend was accelerated after 1945 CE, indicative of a Great Acceleration. We found that European lakes have experienced widespread increases in DI-TP over the 20(th) century and that 33% of these lakes show patterns consistent with a post-1945 CE Great Acceleration. In North America, the proportion of lakes that increased in DI-TP over time is much lower and only 9% exhibited a Great Acceleration of eutrophication. CONCLUSIONS/SIGNIFICANCE: The longer and more widespread history of anthropogenic influence in Europe, the leading cause for the relatively pervasive freshwater eutrophication, provides an important cautionary tale; our current path of intensive agriculture around the world may lead to an acceleration of eutrophication in downstream lakes that could take centuries from which to recover.

Ultrasonic scattering in chocolate and model systems containing sucrose, tripalmitin and olive oil.

Ultrasonic measurements of attenuation versus frequency were made on model systems comprising olive oil, sucrose, and tripalmitin to represent the constituents of chocolate. Corresponding measurements also were made on chocolate flowing in a pipeline at a pilot plant where the temperature, pressure, and temper of the chocolate were precisely controlled and monitored. Experimental results combined with simulation studies indicate that the effect of ultrasonic scattering from tripalmitin crystals in olive oil is modified by the addition of sucrose crystals at a high concentration. It is proposed that the presence of seed crystals in chocolate (temper) cannot be detected ultrasonically in the practical measurement range 1-12 MHz due to a similar process.

Identifying off-target effects and hidden phenotypes of drugs in human cells.

We present a strategy for identifying off-target effects and hidden phenotypes of drugs by directly probing biochemical pathways that underlie therapeutic or toxic mechanisms in intact, living cells. High-content protein-fragment complementation assays (PCAs) were constructed with synthetic fragments of a mutant fluorescent protein ('Venus', EYFP or both), allowing us to measure spatial and temporal changes in protein complexes in response to drugs that activate or inhibit particular pathways. One hundred and seven different drugs from six therapeutic areas were screened against 49 different PCA reporters for ten cellular processes. This strategy reproduced known structure-function relationships and also predicted 'hidden,' potent antiproliferative activities for four drugs with novel mechanisms of action, including disruption of mitochondrial membrane potential. A simple algorithm identified a 25-assay panel that was highly predictive of antiproliferative activity, and the predictive power of this approach was confirmed with cross-validation tests. This study suggests a strategy for therapeutic discovery that identifies novel, unpredicted mechanisms of drug action and thereby enhances the productivity of drug-discovery research.

Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease.

BACKGROUND/AIM: A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function. METHODS: In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks. RESULTS: There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment. CONCLUSIONS: The study failed to show any significant effect of 16 weeks' L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.

"Pray or Prey?" dissociation of semantic memory retrieval from episodic memory processes using positron emission tomography and a novel homophone task.

One problem in studying the neural basis of semantic memory using functional neuroimaging is that it is often difficult to disentangle activation associated with semantic memory retrieval from that associated with episodic memory encoding and retrieval. To address this issue, a novel homophone task was used in which subjects were PET scanned whilst learning a series of real words (e.g., prey). In a subsequent scan, the subjects were presented with homophone pairs (e.g., prey vs pray) and were required to choose the one that had been shown previously. In two corresponding baseline tasks, the subjects were scanned whilst learning and recognizing pronounceable nonwords. Thus, while all of these tasks recruited either episodic memory encoding or retrieval processes, only the homophone tasks involved semantic memory retrieval. A conjunction analysis designed to isolate activation associated with semantic memory retrieval, revealed changes in several left lateral frontal regions (BA 9/10, 9/45), the left middle temporal cortex (BA 21), and in the left inferior temporoparietal cortex (BA 39). In contrast, a conjunction analysis designed to isolate activation associated with episodic memory encoding, revealed significant changes in the left hippocampus, as well as in the frontopolar cortex (BA 10) bilaterally, the left inferior parietal cortex (BA 40), and the left superior temporal gyrus (BA 22, 28). The present results clarify and extend recent attempts to understand the neural basis of semantic memory retrieval, by actively controlling for the confounding effects of episodic memory encoding and retrieval processes.

In vitro high-throughput screening assay for modulators of transcription.

We developed a 96-well microtiter-plate high-throughput screening (HTS) assay for the detection of modulators of transcription. This HTS assay consists of three steps: (1) the in vitro transcription reaction; (2) modification and hybridization of RNA products; and (3) washing and quantification. During the first step, a DNA template containing the promoter of interest upstream of a cassette lacking guanosine residues in one of its strands (G-less cassette) is incubated with nuclear extract and the necessary cofactors/activators and substrates. During the second step, the in vitro synthesized transcripts are digested with RNase T1 and hybridized to two DNA oligonucleotides. One oligonucleotide is biotinylated for trapping of the RNA products to a streptavidin-coated plate, and the other is europium-labeled for detection by time-resolved fluorescence. We show that this assay is highly reproducible and robust, yielding results comparable to those obtained by standard methodologies employing radioactive nucleotide incorporation and gel electrophoresis while offering a very significant advantage in terms of throughput (>2000 assay points per operator per day). We demonstrate the usefulness of the assay for the discovery of small molecule inhibitors of transcription, and applications of this approach for the high-throughput discovery of transcriptional modulators are discussed.

Results of a pilot program for training bar staff in preventing aggression.

One hundred and twenty-one staff from eight bars in Ontario, Canada participated in a three-hour training program that used a peer learning model to teach problem-solving skills regarding the prevention and management of aggressive behavior in bars. Participants showed significant positive changes in knowledge and attitudes regarding effective approaches to preventing aggression. The majority of participants reported that the training made them think about ways they handed problem situations and that they would change the way they handle problems in the future. Participants rated most aspects of the training as very useful, especially the group discussion. The program illustrates the potential for increasing skills and knowledge of bar staff in preventing aggression and associated injury.

Spontaneous mutation frequency and pattern in Big Blue mice fed a vitamin E-supplemented diet.

Endogenous oxidative DNA damage caused by normal cellular processes may play a vital role in carcinogenesis. To directly test the hypothesis that antioxidants will protect DNA from oxidative damage in vivo, Big Blue((R)) mice were fed either a control diet (66 IU vitamin E/kg diet) or a high-dose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,l-alpha-tocopherol acetate from conception until 3 months of age. Using the standard Big Blue((R)) protocol, 15.5 million plaque forming units (pfu) were examined from five tissues (heart, liver, adipose tissue, thymus, and testis) of three control and three high-dose vitamin E supplemented male mice generating 433 mutants, which represented 373 independent mutations upon sequencing the lacI transgene. The alpha-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed little if any with vitamin E supplementation. In adipose tissue, which accumulated the highest levels of vitamin E, mutation frequency was significantly reduced with high-dose vitamin E supplementation (P = 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P = 0.40). When data from all tissues were combined, a reduction in G:C --> T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d-alpha-tocopherol acetate.