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Biomineralization processes govern the formation of hierarchical hard tissues such as bone and teeth in living organisms, and mimicking these processes could lead to the design of new materials with specialized properties. However, such advances require structural characterization of the proteins guiding biomineral formation to understand and mimic their impact. In their "active" form, biomineralization proteins are bound to a solid surface, severely limiting our ability to use many conventional structure characterization techniques. Here, solid-state NMR spectroscopy was applied to study the intermolecular interactions of amelogenin, the most abundant protein present during the early stages of enamel formation, in self-assembled oligomers bound to hydroxyapatite. Intermolecular dipolar couplings were identified that support amelogenin dimer formation stabilized by residues toward the C-termini. These dipolar interactions were corroborated by molecular dynamics simulations. A β-sheet structure was identified in multiple regions of the protein, which is otherwise intrinsically disordered in the absence of hydroxyapatite. To our knowledge, this is the first intermolecular protein-protein interaction reported for a biomineralization protein, representing an advancement in understanding enamel development and a new general strategy toward investigating biomineralization proteins., (Copyright © 2018 Biophysical Society. All rights reserved.)

Aurorae are detected from all the magnetized planets in our Solar System, including Earth. They are powered by magnetospheric current systems that lead to the precipitation of energetic electrons into the high-latitude regions of the upper atmosphere. In the case of the gas-giant planets, these aurorae include highly polarized radio emission at kilohertz and megahertz frequencies produced by the precipitating electrons, as well as continuum and line emission in the infrared, optical, ultraviolet and X-ray parts of the spectrum, associated with the collisional excitation and heating of the hydrogen-dominated atmosphere. Here we report simultaneous radio and optical spectroscopic observations of an object at the end of the stellar main sequence, located right at the boundary between stars and brown dwarfs, from which we have detected radio and optical auroral emissions both powered by magnetospheric currents. Whereas the magnetic activity of stars like our Sun is powered by processes that occur in their lower atmospheres, these aurorae are powered by processes originating much further out in the magnetosphere of the dwarf star that couple energy into the lower atmosphere. The dissipated power is at least four orders of magnitude larger than what is produced in the Jovian magnetosphere, revealing aurorae to be a potentially ubiquitous signature of large-scale magnetospheres that can scale to luminosities far greater than those observed in our Solar System. These magnetospheric current systems may also play a part in powering some of the weather phenomena reported on brown dwarfs.

Objective: The aim of this study was to measure the internal dose received by family members from ingestion of radioactive contamination after outpatient therapy., Materials and Methods: Advice was given to minimise transfer of radioiodine. Home visits were made approximately 2, 7 and 21 days after treatment to measure radioactivity in the thyroids of family members. A decay correction was applied to radioactivity detected assuming ingestion had occurred at the earlier contact time, either the day of treatment or the previous home visit. An effective half-life of 6 or 7 days was used depending on age. Thyroid activity was summed if activity was found at more than one visit in excess of the amount attributable to radioactive decay. Effective dose (ED) was calculated using ICRP72., Results and Discussion: Fifty-three adults and 92 children, median age 12 (range 4-17) years participated. Median administered activity was 576 (range 329-690) MBq (131)I. Thyroid activity ranged from 0 to 5.4 kBq in the adults with activity detected in 17. Maximum adult ED was 0.4 mSv. Thyroid activity ranged from 0 to 11.8 kBq in the children with activity detected in 26. The two highest values of 5.0 and 11.8 kBq occurred in children aged 5 and 14 years from different families. Eighty-five children had no activity or <1 kBq detected. ED was <0.2 mSv in 86 out of 92 children (93%). Previous published data showed 93% of children received an ED

The purpose of this study was to assess the level of agreement between two techniques commonly used to measure exogenous carbohydrate oxidation (CHO(EXO)). To accomplish this, seven healthy male subjects (24 +/- 3 yr, 74.8 +/- 2.1 kg, V(O2(max)) 62 +/- 4 ml x kg(-1) x min(-1)) exercised at 50% of their peak power for 120 min on two occasions. During these exercise bouts, subjects ingested a solution containing either 144 g glucose (8.7% wt/vol glucose) or water. The glucose solution contained trace amounts of both [U-13C]glucose and [U-14C]glucose to allow CHO(EXO) to be quantified simultaneously. The water trial was used to correct for background 13C enrichment. 13C appearance in the expired air was measured using isotope ratio mass spectrometry, whereas 14C appearance was quantified by trapping expired CO(2) in solution (using hyamine hydroxide) and adding a scintillator before counting radioactivity. CHO(EXO) measured with [13C]glucose ([13C]CHO(EXO)) was significantly greater than CHO(EXO) measured with [14C]glucose ([14C]CHO(EXO)) from 30 to 120 min. There was a 15 +/- 4% difference between [13C]CHO(EXO) and [14C]CHO(EXO) such that the absolute difference increased with the magnitude of CHO(EXO). Further investigations suggest that the difference is not because of losses of CO2 from the trapping solution before counting or an underestimation of the "strength" of the trapping solution. Previous research suggests that the degree of isotopic fractionation is small (S. C. Kalhan, S. M. Savin, and P. A. Adam. J Lab Clin Med89: 285-294, 1977). Therefore, the explanation for the discrepancy in calculated CHO(EXO) remains to be fully understood.

The first purpose of the study was to examine whether combined ingestion of glucose and sucrose at an intake rate of 1.2 g/min would lead to higher oxidation rates compared with the ingestion of an isocaloric amount of glucose or sucrose alone. The second aim of the study was to investigate whether a mixture of glucose and sucrose when ingested at a high rate (2.4 g/min) would result in exogenous CHO oxidation rates higher than 1.2 to 1.3 g/min. Eight trained cyclists (maximal oxygen consumption: 64 +/- 2 mL . kg -1 . min -1 , mean +/- SE) performed 5 exercise trials in random order. Each trial consisted of 120 minutes of cycling at 50% maximum power output (63% +/- 2% maximal oxygen consumption), whereas subjects received a solution providing either 1.2 g/min of glucose (GLU), 1.2 g/min of sucrose (SUC), 0.6 g/min of glucose + 0.6 g/min of sucrose (M-GLU+SUC), 1.2 g/min of glucose + 1.2 g/min of sucrose (H-GLU+SUC), or water (WAT). Peak exogenous CHO oxidation rates in the H-GLU+SUC trial (1.20 +/- 0.07 g/min) were significantly higher ( P < .01) compared with the GLU, M-GLU+SUC, and SUC trials (0.77 +/- 0.04, 0.90 +/- 0.07, 0.98 +/- 0.04 g/min, respectively). Furthermore, peak exogenous CHO rates in M-GLU+SUC and SUC trials were significantly higher ( P < .05) compared with the GLU trial. In conclusion, combined ingestion of moderate amounts of glucose and sucrose (144 g) during cycling exercise resulted in approximately 21% higher exogenous CHO oxidation rates compared with the ingestion of an isocaloric amount of glucose. Furthermore, when a mixture of glucose and sucrose was ingested at high rates (2.4 g/min), exogenous CHO oxidation rates reached peak values of approximately 1.20 g/min.

The purpose of the present study was to examine whether combined ingestion of a large amount of fructose and glucose during cycling exercise would lead to exogenous carbohydrate oxidation rates >1 g/min. Eight trained cyclists (maximal O(2) consumption: 62 +/- 3 ml x kg(-1) x min(-1)) performed four exercise trials in random order. Each trial consisted of 120 min of cycling at 50% maximum power output (63 +/- 2% maximal O(2) consumption), while subjects received a solution providing either 1.2 g/min of glucose (Med-Glu), 1.8 g/min of glucose (High-Glu), 0.6 g/min of fructose + 1.2 g/min of glucose (Fruc+Glu), or water. The ingested fructose was labeled with [U-(13)C]fructose, and the ingested glucose was labeled with [U-(14)C]glucose. Peak exogenous carbohydrate oxidation rates were approximately 55% higher (P < 0.001) in Fruc+Glu (1.26 +/- 0.07 g/min) compared with Med-Glu and High-Glu (0.80 +/- 0.04 and 0.83 +/- 0.05 g/min, respectively). Furthermore, the average exogenous carbohydrate oxidation rates over the 60- to 120-min exercise period were higher (P < 0.001) in Fruc+Glu compared with Med-Glu and High-Glu (1.16 +/- 0.06, 0.75 +/- 0.04, and 0.75 +/- 0.04 g/min, respectively). There was a trend toward a lower endogenous carbohydrate oxidation in Fruc+Glu compared with the other two carbohydrate trials, but this failed to reach statistical significance (P = 0.075). The present results demonstrate that, when fructose and glucose are ingested simultaneously at high rates during cycling exercise, exogenous carbohydrate oxidation rates can reach peak values of approximately 1.3 g/min.

It is generally accepted that the quality of myocardial images deteriorates with increasing patient weight. This is attributed to a reduction of counts detected from the myocardium. In this paper we have looked at the count reduction in obese patients and suggest a workable algorithm to increase the injected activity to compensate for this loss of count. In this prospective study, 64 consecutive patients with normal myocardial images were selected to include a weight range of 50-120 kg. The height, weight and gender of patients were noted. Each patient had two studies (total of 128 studies), one at rest and one following stress with adenosine and 20-40 W bicycle exercise. Total myocardial counts were calculated from the back-projected views. The total myocardial counts per MBq of the injected activity were calculated. There was no significant difference in the injected activity and the size of the heart (pixel length of heart) between stress and rest, or gender of the patient. The normalized myocardial counts were not different between men and women, but the counts were slightly, although not significantly, higher ( P=NS) with adenosine and exercise (mean of 243 x 10(3) counts) compared to rest images (229 x 10(3) counts). There was a significant progressive loss of counts in patients with increasing weight, body mass index or body surface area ( P<0.001). There was no significant difference in the changes in counts with weight between male and female, or rest and stress studies. The combined data from all the studies were used to calculate the correlation coefficient and the slope of the line for reduction of cardiac counts with a patient's weight, body mass index, and body surface area. The best correlation was with patient weight ( r=0.58, P<0.001). This was used to calculate the increase in injection activity with increasing weight to maintain the same average counts as achieved in a 70 kg patient with a 400 MBq injection. We suggest that the injection activity should increase from 100% for a 70 kg patient to 140% for 110 kg, 200% for 140 kg, and 250% for a 150 kg patient.

In this study we examined the delivered activity of radiopharmaceuticals injected into patients and the various factors which lead to incomplete delivery. Four commonly used 99Tcm radiopharmaceuticals were included, namely pertechnetate, methylene diphosphonate (MDP), macro-aggregated albumin (MAA) and tetrofosmin. There was no appreciable residual activity after injection of pertechnetate and MDP other than that due to the dead space in syringes (0.06 ml, 4% of measured activity). However, there was considerable residual activity following an MAA injection. This was particularly dependent on the radiopharmaceutical residence time in the syringe prior to injection. If MAA was pre-dispensed there was up to 80% of activity remaining in the syringe following injection. We have shown that this activity is not bound and can be decreased by agitating the syringe prior to the injection. For tetrofosmin, the activity remaining in the syringe was shown to be mostly due to adsorption of the tetrofosmin onto the plastic syringe (up to 30% of the activity); in particular, onto the rubber plunger. The amount of binding probably depends on the formulation of the rubber plunger and the plastic barrel, which varies between manufacturers. Of the three commonly used syringe brands (Becton-Dickinson, Sherwood, and Braun syringes) the Braun syringes were shown to have the least binding (6%) and would be most suitable for tetrofosmin injection. We recommend the use of Braun syringes for tetrofosmin. We also recommend that pre-dispensed MAA injections should be gently agitated before injection into the patient. No special precautions are necessary for pertechnetate or MDP injections.

We have assessed the usefulness of a radionuclide dilution method for estimation of ascitic fluid volume. 99Tc(m) macroaggregated albumin (10 MBq) was injected into the peritoneal fluid. Multiple samples were taken using a trocath peritoneal dialysis catheter over a 4-h period. Blood samples were taken at the same time and a 4-h urine collection was made during the study. At 4 h a controlled drainage of ascitic fluid, followed by suction drainage, was used and a total drained volume measured. For comparison, peritoneal volumes were measured from the radioactivity of peritoneal fluid activity samples using dilution techniques. The estimated peritoneal fluid volume using the radionuclide method was consistently higher than the drained volume. This was attributed to either a lack of uniform distribution of the activity in the peritoneal cavity by 4 h or early breakdown and absorption of activity from the peritoneal cavity. In two patients it was not possible to measure a volume due to poor distribution of the radionuclide in the peritoneal fluid. We found that in our group of patients the radionuclide dilution is of little value in estimating the peritoneal fluid volume.

Irradiation of pregnant women either in the workplace or as a consequence of clinical diagnosis is often unavoidable. This paper reviews the issues relating to this topic. For clinical exposures the "missed period" rule is applied prior to most clinical studies. However normal physiological variations in the menstrual cycle may need to be understood. The possible effects of irradiation, both deterministic and stochastic, on the fetus are also described. The decision process in relation to irradiation of a pregnant or potentially pregnant patient is discussed in terms of the regulatory guidance. A different approach is needed for studies which clearly involve a low dose to the uterus compared with studies involving a high dose, including therapy. The issue of a pregnant or potentially pregnant worker in nuclear medicine is also considered. Restrictions on certain work activities may be necessary once pregnancy is declared. Other areas considered are biomedical research and also the potential for exposure of pregnant woman in the home or in the workplace as a consequence of others having a nuclear medicine study.

Detrimental effects on the thyroid of the developing fetus as a result of iodine-131 treatment for thyrotoxicosis of the mother in the first trimester of pregnancy are discussed. Dose estimations under typical clinical circumstances yield a fetal thyroid dose of 100- 450 Sv. This dose may increase considerably if the blood concentration of (131)I in the mother remains high. Under such circumstances there may be fetal thyroid dysfunction, which can lead to severe abnormalities.

A reduction in acquisition times from 10 to 5 min for scintimammography does not reduce the diagnostic value of the study when imaging for detection of breast lesions. The test showed an overall sensitivity of 96%, specificity of 100% and accuracy of 98% for breast lesions visualized on both 5 and 10 min acquisitions. Even if lymph node detection is the primary concern of the study, longer scan times do not increase the sensitivity of the test (40% on both 5 and 10 min). Scintimammography is poor at detecting lymph nodes (sensitivity 40%, specificity 69-82%) and is not useful for assessing lymph node involvement. A reduction in imaging times appeared to be consistent on both camera systems tested, which have very different display outputs. This would indicate that other departments may be able to reduce times on their systems without affecting the quality of the study. The detection of breast lesions was also consistent between reporters.

Patients who receive radioiodine (iodine-131) treatment for hyperthyroidism (195-800 MBq) emit radiation and represent a potential hazard to other individuals. Critical groups amongst the public are fellow travellers on the patient's journey home from hospital and members of the patient's family, particularly young children. The dose which members of the public are allowed to receive as a result of a patient's treatment has been reduced in Europe following recently revised recommendations from ICRP. The annual public dose limit is 1 mSv, though adult members of the patient's family are allowed to receive higher doses, with the proviso that a limit of 5 mSv should not be exceeded over 5 years. Unless the doses received during out-patient administration of radioiodine can be demonstrated to comply with these new limits, hospitalisation of patients will be necessary. The radiation doses received by family members (35 adults and 87 children) of patients treated with radioiodine at five UK hospitals were measured using thermoluminescent dosimeters mounted in wrist bands. Families were given advice (according to current practice) from their treatment centre about limiting close contact with the patient for a period of time after treatment. Doses measured over 3-6 weeks were adjusted to give an estimate of values which might have been expected if the dosimeters had been worn indefinitely. Thirty-five passengers accompanying patients home after treatment also recorded the dose received during the journey using electronic (digital) personal dosimeters. For the "adjusted" doses to infinity, 97% of adults complied with a 5-mSv dose limit (range:0.2-5.8 mSv) and 89% of children with a 1-mSv limit (range: 0.2-7.2 mSv). However 6 of 17 children aged 3 years or less had an adjusted dose which exceeded this 1 mSv limit. The dose received by adults during travel was small in comparison with the total dose received. The median travel dose was 0.03 mSv for 1 h travel (range: 2 microSv-0.52 mSv for 1 h of travel time). These data suggest that hyperthyroid patients can continue to be treated with radioiodine on an out-patient basis, if given appropriate radiation protection advice. However, particular consideration needs to be given to children aged 3 years or younger. Admission to hospital is not warranted on radiation protection grounds.

The mean rate of non-attendance at this hospital is 16%, with the Nuclear Medicine Department averaging 4%. Although only a small percentage, increasing demand for nuclear medicine studies has led to a need for greater efficiency to reduce financial losses. From April 1995 to March 1996, 104 patients did not attend over a range of 16 studies. We examined the types of study, patients and costs. The costs of wasted staff time, camera time and radiopharmaceutical ranged from pound sterling 24 (99Tc(m) thyroid) to pound sterling 470 (75Se cholesterol adrenal). This results in a loss equivalent to pound sterling 7258 over the year. There was no significant difference in non-attendance rates between different types of procedure, source and type of referral, or in the three age groups: children, working and retired population. Finally, we looked at cultural origins, segregating the groups into Asian and European origins based on surname. A significantly higher proportion of patients of Asian origin did not attend. This study has shown that it may be of benefit to target specific groups and tests. For example, at City Hospital, perhaps we should concentrate on our Asian community to ensure they understand fully what the study involves. It would also be worthwhile targeting the more expensive nuclear medicine studies.

Recent legislation which has been passed in Europe comprises the Basic Safety Standard (BSS) [1] and the Medical Exposure Directive (MED) [2]. These documents are the implementation of ICRP's report 60 [3], and ICRP publication 73 [4] expands ICRP60 for medical applications. The BSS repeals 80/836/EURATOM and 84/467/EURATOM amongst other EURATOM directives. The MED repeals 84/466/EURATOM, which is the patient protection directive. Member States (MS) are required to implement both the BSS and the MED by the 13 May 2000, and this is where input from individual members of the EANM is very important. Within every MS it is vital to ensure that the key points are debated properly, so that legislation in the countries of Europe is reasonable.

The possible detrimental effects on the developing embryo subsequent to irradiation are discussed. The doses to the embryo or fetus encountered for the most common procedures in diagnostic nuclear medicine are evaluated with respect to the threshold doses and the risks per cGy. The threshold dose for fatal and non-fatal malformations or other defects is, at the lowest estimate, 5-10 cGy. The dose which the embryo or fetus receives from diagnostic nuclear medicine is below 1 cGy. For the induction of fatal cancer and for genetic defects no threshold dose is assumed. The risk for the induction of cancer is 0.03%-0.05% per cGy. The risk for the induction of genetic defects is even lower (0.024%-0.099% per cGy). It is concluded that for common diagnostic nuclear medicine procedures the risk of detrimental effects on the embryo or fetus due to radiation is negligible. On the basis of present knowledge there are no radiation safety indications for abortus provocatus as a consequence of a diagnostic nuclear medicine study.

This is a historical review of selected events in radiation protection of medical relevance since the discovery of X-rays. The report concentrates on the period 1895-1970. Key points were difficulty of measuring dose, rapid dissemination of the use of radiation for all sorts of illness, and regulation by professional bodies rather than by legislation. Both World Wars saw a huge expansion in the use of ionizing radiation, but the second war prevented international collaboration, which had begun formally in 1925. Early radiation deaths, and nuclear accidents have caused concerns about radiation safety, and although dose limits have been successively reduced, these concerns have not been overcome. Since the Second World War radiation safety has been subject to more and more legislation although professional bodies still have an important advisory role. Development of the main radiation safety committees both in the UK, US and internationally is described with emphasis on the particular role of the British Institute of Radiology.

We have assessed the potential impact of a regular half-day session on Saturday only, or Sunday only, and compared this with a whole weekend on-call service for lung scans. We predicted the effect of these services using the data gathered over 2 years (1992-94), looking at the results of lung scans and admission and discharge of patients. The on-call service in all three cases would be justified if resources from the savings on patient discharge and bed availability could be earmarked for the nuclear medicine service. The cost of introducing such an on-call service for the department would be Pounds 3000 per year per session at the weekend and up to Pounds 10,000 per year for a full weekend on-call service. The total cost to the hospital would be negligible.

The number of nuclear medicine studies is increasing and they are becoming more complex and time-consuming. In particular, this is true of myocardial perfusion investigations. We use a one-day protocol for these studies, utilizing 99Tc(m)-MIBI or 99Tc(m)-tetrofosmin with tomographic rest images (250 MBq) acquired in the morning and exercise images (750 MBq) approximately 4 h later after pharmacological stress. Imaging technologists are concerned about continual exposure to 1000 MBq 99Tc(m) per study. Radiation doses were measured during rest (1.0 microSv, n = 18), exercise (2.5 microSv, n = 18) and stress administration (2.0 microSv, n = 16), giving a total dose of 5.5 microSv per combined cardiac study. We have previously shown that the average dose per radionuclide study (excluding myocardial perfusion studies) is 1.5 microSv. Although 5.5 microSv is higher, a technologist is highly unlikely to exceed current dose limits. New EC legislation, however, is expected to reduce these limits, which may lead to more classified workers. Pregnant technologists should avoid, if possible, combined cardiac studies, especially if performing other nuclear medicine duties.

This paper reviews the published data relating to the radiation hazards associated with nuclear medicine outpatients. It is discussed both in the context of the current UK advice as well as potential guidelines following the recommendations in ICRP 60. For diagnostic studies there is little need for restrictions. The main exceptions are for a prolonged journey home by public transport with high levels of 99Tcm and for the situation of an outpatient given 111In who has to look after a fretful infant. The main problem occurs following the administration of 131I therapy for thyrotoxicosis. The principal hazards are associated with external exposure; radiation doses from ingestion due to contamination are small. Restrictions should only be necessary for administered activities greater than 400 MBq (e.g. public transport, return to work, sleeping with partner). With such restrictions it is considered that 131I therapy for thyrotoxicosis can continue to be given on an outpatient basis.

It is unclear whether bile acid absorption is affected by ileoanal pouch construction. Bile acid absorption was measured in the abdomen of 16 patients with pouches (nine with good and seven with poor pouch function based on a clinical score) and in six patients with an end ileostomy using a radiolabelled synthetic bile acid (75SeHCAT) enema and dynamic scintigraphy. The median (interquartile range) 75SeHCAT absorption was 81 (79-87) per cent in patients with ileostomy, 46 (43-53) per cent in patients having well functioning pouches, and 24 (18-38) per cent in the group with poor pouch function (P < 0.01). Log transformation of the absorption curves revealed a two-component uptake (fast component t1/2 = 1.4-7.2 min; slow component t1/2 = 16-144 min) in all patients with ileostomy, in eight of nine patients with pouches with good function, and in one of seven patients with a poorly functioning pouch (P < 0.05); in the other six patients with poorly functioning pouches, only the slow component of absorption was present. This test showed significantly reduced bile acid absorption in patients with an ileoanal pouch and gave an objective discrimination between well and poorly functioning pouches.

This study investigated the hypothesis that some features of functional gastrointestinal disorders may be associated with abnormalities of ileocaecal transit by measuring ileocaecal transit using a scintigraphic technique in 43 patients with chronic constipation, 20 patients with irritable bowel syndrome (IBS), and 18 control subjects. Subjects ingested enteric coated capsules, which delivered 111-indium radionuclide to the distal ileum. Gammacamera images were acquired at hourly intervals until caecal filling was complete. Ileocaecal transit was defined as the time between peak scintigraphic activity in the terminal ileum and peak activity in the caecum. The mean (SD) ileocaecal transit of 103 (50) minutes in patients with IBS was significantly faster than that in control subjects (mean (SD) ileocaecal transit 174 (78) minutes, p < 0.002). There were no significant differences in ileocaecal transit between patients with chronic idiopathic constipation and the control subjects, or between patients with constipation predominant and diarrhoea predominant IBS. This study developed a practical scintigraphic method of measuring ileocaecal transit. The rapid ileocaecal transit in both the constipation and diarrhoea predominant forms of IBS suggests that bloating may not after all result from delayed ileal emptying.

This study describes a graphic presentation of the results of a simplified segmental colonic transit model. This study requires three sets of images on three consecutive days after intake of indium-111 resin capsule at each time point. The per cent of ingested activity is calculated in each region of the colon and in the faeces. The program uses standard PC compatible graphic package, CorelDRAW (Corel Corporation). The report for the patients' notes consists of three schematic diagrams of colon with regions identified and a pot representing the faecal activity. The per cent of administered activity in each region and pot is both printed and represented by shades of grey (white representing 0% and black 100% activity), for each region and the pot. The distribution of activity is clearly seen at each time point and the report is presented on single A4 size sheet of paper. Using a simplified colonic study protocol it is possible to produce clinician friendly reports on a single sheet of paper.