Thyroid function status evaluation in patient post-radiotherapy for nasopharyngeal carcinoma: A retrospective study.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is among the most common malignancy in Malaysia. Radiationinduced hypothyroidism has been reported in other countries. However, in Malaysia, no studies were ever done to determine the effect of radiation on hypothyroidism. The objective of this study is to evaluate the practice of taking thyroid function test (TFT) and determine hypothyroidism post-radiation in patients with NPC. MATERIALS AND METHODS: A retrospective study on the symptoms and results of TFT according to the dosage of intensity-modulated radiotherapy (IMRT) given to patients with NPC. Data were traced and analysed. RESULTS: A total of 78 patients were identified. All patients received IMRT with 33-35 fractions of radiotherapy (RT) with total dosage of 66-70 Gray given. Not all patients had their thyroid function status measured routinely. Twelve patients did have symptoms of hypothyroidism. TFT were obtained in this group but the results were normal. No correlation was found between RT and hypothyroidism. CONCLUSION: There was no correlation between IMRT and the development of hypothyroidism. A prospective study with better control of inclusion and exclusion criteria, and longer follow-up period with TFT, is needed to demonstrate the consistency of these findings.

Resonant Inelastic X-Ray Scattering Reveals Hidden Local Transitions of the Aqueous OH Radical.

Resonant inelastic x-ray scattering (RIXS) provides remarkable opportunities to interrogate ultrafast dynamics in liquids. Here we use RIXS to study the fundamentally and practically important hydroxyl radical in liquid water, OH(aq). Impulsive ionization of pure liquid water produced a short-lived population of OH(aq), which was probed using femtosecond x-rays from an x-ray free-electron laser. We find that RIXS reveals localized electronic transitions that are masked in the ultraviolet absorption spectrum by strong charge-transfer transitions-thus providing a means to investigate the evolving electronic structure and reactivity of the hydroxyl radical in aqueous and heterogeneous environments. First-principles calculations provide interpretation of the main spectral features.

Humanistic and economic outcomes of pharmacist-provided medication review in the community-dwelling elderly: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Recent reviews have shown that pharmacist-provided medication review in the elderly can improve clinical outcomes and reduce medication discrepancies compared with usual care. However, none determined whether these translate to improved humanistic and economic outcomes. This review sought to evaluate the effects of medication review on health-related quality of life (HRQoL) and healthcare costs in the elderly. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane library for studies published in English from inception to 31 August 2015 was conducted. The review included studies lasting at least 3 months that randomly assigned community-dwelling participants aged at least 65 years to receive either pharmacist-provided medication review or usual care. Studies set in nursing homes were excluded. RESULTS AND DISCUSSION: The review identified 25 studies that included 15 341 participants and lasted between 3 and 36 months. Twenty and 13 studies reported HRQoL and economic outcomes, respectively. Overall, there was no significant difference in HRQoL and healthcare costs between pharmacist-provided medication review and usual care. Meta-analysis of studies that reported the 36-item Short-Form Health Survey found significant differences in favour of usual care in the body pain (mean difference: 2·94, 95% CI: 0·54-5·34, P = 0·02) and general health perception (mean difference: 1·83, 95% CI: 0·16-3·50, P = 0·03) domains, whereas there were no significant differences in other domains. Meta-analysis of the EuroQol-5D utility (mean difference: -0·01, 95% CI: -0·02-0·01, P = 0·57) and visual analogue scale (mean difference: 0·01, 95% CI: -3·24-3·26, P = 1·00) found no significant differences. Costs of hospitalization, medication and other healthcare resources consumed were similar between groups. WHAT IS NEW AND CONCLUSION: Humanistic and economic outcomes of pharmacist-provided medication review were largely similar to those of usual care. Further research using more robust methodology is needed to determine whether improved medication management can improve HRQoL and reduce healthcare costs. Careful thought should be given to capturing relevant outcomes that reflect the potential benefits of this intervention.

Warming and redistribution of nitrogen inputs drive an increase in terrestrial nitrous oxide emission factor.

Anthropogenic nitrogen inputs cause major negative environmental impacts, including emissions of the important greenhouse gas N2O. Despite their importance, shifts in terrestrial N loss pathways driven by global change are highly uncertain. Here we present a coupled soil-atmosphere isotope model (IsoTONE) to quantify terrestrial N losses and N2O emission factors from 1850-2020. We find that N inputs from atmospheric deposition caused 51% of anthropogenic N2O emissions from soils in 2020. The mean effective global emission factor for N2O was 4.3 ± 0.3% in 2020 (weighted by N inputs), much higher than the surface area-weighted mean (1.1 ± 0.1%). Climate change and spatial redistribution of fertilisation N inputs have driven an increase in global emission factor over the past century, which accounts for 18% of the anthropogenic soil flux in 2020. Predicted increases in fertilisation in emerging economies will accelerate N2O-driven climate warming in coming decades, unless targeted mitigation measures are introduced.

Evaluation of the physicochemical properties and compaction behavior of melt granules produced in microwave-induced and conventional melt granulation in a single pot high shear processor.

Recently, microwave-induced melt granulation was shown to be a promising alternative to conventional melt granulation with improved process monitoring capabilities. This study aimed to compare the physicochemical and compaction properties of granules produced from microwave-induced and conventional melt granulation. Powder admixtures comprising equivalent proportions by weight of lactose 200 M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350 under the influence of microwave-induced and conventional heating in a 10-L single pot high shear processor. The properties of the granules and compacts produced from the two processes were compared. Relative to conventional melt granulation, the rates at which the irradiated powders heated up in microwave-induced melt granulation were lower. Agglomerate growth proceeded at a slower rate, and this necessitated longer massing durations for growth induction. These factors prompted greater evaporative moisture losses from the melt granules. Additionally, nonuniform heating of the powders under the influence of microwaves led to increased inter-batch variations in the binder contents of resultant melt granules and a reliance of content homogeneity on massing duration. Agglomerate growth proceeded more rapidly under the influence of conventional heating due to the enhanced heating capabilities of the powders. Melt granules produced using the conventional method possessed higher moisture contents and improved content homogeneity. The compaction behavior of melt granules were affected by their mean sizes, porosities, flow properties, binder, and moisture contents. The last two factors were responsible for the disparities in compaction behavior of melt granules produced from microwave-induced and conventional melt granulation.

Real-world impact of anti-HER2 therapy-related cardiotoxicity in patients with advanced HER2-positive breast cancer.

BACKGROUND: Anti-HER2 therapy-related cardiotoxicity is well described in the context of clinical trials, particularly in the setting of early stage disease, but there is more limited data in advanced breast cancer and in the real world setting. MATERIAL AND METHODS: A prospectively-maintained registry database with 312 consecutive patients diagnosed with HER2 positive advanced breast cancer in Australia was analysed. RESULTS: 287 patients (92%) received anti-HER2 therapy, 17 (6%) experienced anti-HER2 therapy-related cardiotoxicity. Patients who experienced cardiotoxicity were more likely to have ≥2 risk factors for cardiotoxicity (OR 3.9 95% CI 1.4-11.3 p = 0.01). A prior diagnosis of cardiovascular disease was significantly associated with cardiotoxicity (OR 7.1 95% CI 1.3-39.5). Cardiotoxicity resolved on imaging in 65% of patients; there was no association between severity and resolution. 11 patients (65%) received cardiologist input. Of the patients who developed cardiotoxicity, 12 patients (71%) received further anti-HER2 therapy in the first- or second-line setting without recurrent cardiotoxicity. DISCUSSION AND CONCLUSION: Therapy-related cardiotoxicity is an uncommon complication of anti-HER2 therapy in the real world setting. Cardiac toxicity resolved in the majority of affected patients, and further anti-HER2 therapy was administered without recurrence of cardiac issues. Our data suggests anti-HER2 therapy can be safely given in routine care, even in patients with risk factors for toxicity.

Observation of the fastest chemical processes in the radiolysis of water.

Elementary processes associated with ionization of liquid water provide a framework for understanding radiation-matter interactions in chemistry and biology. Although numerous studies have been conducted on the dynamics of the hydrated electron, its partner arising from ionization of liquid water, H2O+, remains elusive. We used tunable femtosecond soft x-ray pulses from an x-ray free electron laser to reveal the dynamics of the valence hole created by strong-field ionization and to track the primary proton transfer reaction giving rise to the formation of OH. The isolated resonance associated with the valence hole (H2O+/OH) enabled straightforward detection. Molecular dynamics simulations revealed that the x-ray spectra are sensitive to structural dynamics at the ionization site. We found signatures of hydrated-electron dynamics in the x-ray spectrum.

Microwave-assisted drying of pharmaceutical granules and its impact on drug stability.

The advent of microwave technology has intensified the search for pharmaceuticals amenable to microwave processing. This study investigated the influences of powder load, diluent particle size and amount of granulating liquid employed on the microwave-assisted drying and stability of acetylsalicylic acid (ASA)-loaded granules in a single pot high shear processor. Powder load affected the profiles, rate and extent of drying. Drying was more dependent on the size and structural properties of granules rather than their surface areas as heat was generated volumetrically. Increased granule size brought about by increasing the size of diluent particles and amount of granulating liquid resulted in higher drying rates. Drug stability was negatively correlated to the drying time of granules.

A study on microwave-induced melt granulation in a single pot high shear processor.

Microwave-induced high shear melt granulation was compared with conventional melt granulation performed in the same processor. Admixtures of lactose 200M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350. Different heating mechanisms in the two processes necessitated the use of different parameters for process monitoring and control. Mixer power consumption was suitable for monitoring agglomerate growth under microwave-induced heating. Product temperature was a better indicator of agglomeration propensity in conventional melt granulation. These were attributed to the disparities in heat acquisition rates and heating uniformities of the powders as well as variation in baseline mixer power consumption between the two processes.

Migrating esophageal foreign bodies.

UNLABELLED: Ingested foreign bodies which migrate extraluminally, although rare in occurrence, are fraught with the potential to cause life-threatening complications. PURPOSE OF THE STUDY: To discuss the management of this pathology. MATERIAL AND METHODS: A series of four patients with such occurrences is presented. CONCLUSION: A discussion on the safe management of such seemingly innocuous foreign bodies allows the authors to propose a therapeutical algorythm.

Dielectric properties of pharmaceutical materials relevant to microwave processing: effects of field frequency, material density, and moisture content.

The rising popularity of microwaves for drying, material processing and quality sensing has fuelled the need for knowledge concerning dielectric properties of common pharmaceutical materials. This article represents one of the few reports on the density and moisture content dependence of the dielectric properties of primary pharmaceutical materials and their relevance to microwave-assisted processing. Dielectric constants (epsilon') and losses (epsilon'') of 13 pharmaceutical materials were measured over a frequency range of 1 MHz-1 GHz at 23 +/- 1 degrees C using a parallel-electrode measurement system. Effects of field frequency, material density and moisture content on dielectric properties were studied. Material dielectric properties varied considerably with frequency. At microwave frequencies, linear relationships were established between cube-root functions of the dielectric parameters [symbols: see text] and density which enabled dielectric properties of materials at various densities to be estimated by regression. Moisture content was the main factor that contributed to the disparities in dielectric properties and heating capabilities of the materials in a laboratory microwave oven. The effectiveness of a single frequency density-independent dielectric function for moisture sensing applications was explored and found to be suitable within low ranges of moisture contents for a model material.

Ultrasonographic characteristics of soft tissue tumours in dogs.

OBJECTIVE: To identify and describe the ultrasonographic features of soft tissue tumours in dogs. PROCEDURE: Superficial soft tissue tumours of various histological types, including mast cell tumours (MCTs) and soft tissue sarcomas (STSs), were evaluated. Ultrasound was used to visualise internal characteristics of the tumour, including vascularity. Tumours were categorised according to size, shape, margin definition, tissue plane mobility, echogenicity, echotexture, acoustic shadowing or enhancement and vessel distribution. Objective measurements of intratumoural blood flow included velocities and maximal perfused cross-sectional area (fractional area). Logistic regression models incorporating a variety of data were used in an attempt to predict the histopathological type of tumours. RESULTS: The logistic regression model defined by the parameters echotexture, margin definition and presence of subcapsular vessels was highly predictive of MCTs (> 73%; P = 0.024). Several other trends, including a larger size for STSs and less vascularity for both MCTs and STSs, were observed, but did not reach statistical significance. CONCLUSION: This preliminary study has shown the potential diagnostic value of ultrasound in differentiating soft tissue tumours. However, at present, ultrasound cannot replace biopsy and histopathological evaluation for tumour diagnosis.

Infrared spectra and ab initio calculations for the F- -(CH4)n (n = 1-8) anion clusters.

Infrared spectra of mass-selected F- -(CH4)n (n = 1-8) clusters are recorded in the CH stretching region (2500-3100 cm-1). Spectra for the n = 1-3 clusters are interpreted with the aid of ab initio calculations at the MP2/6-311++G(2df 2p) level, which suggest that the CH4 ligands bind to F- by equivalent, linear hydrogen bonds. Anharmonic frequencies for CH4 and F--CH4 are determined using the vibrational self-consistent field method with second-order perturbation theory correction. The n = 1 complex is predicted to have a C3v structure with a single CH group hydrogen bonded to F-. Its spectrum exhibits a parallel band associated with a stretching vibration of the hydrogen-bonded CH group that is red-shifted by 380 cm-1 from the nu1 band of free CH4 and a perpendicular band associated with the asymmetric stretching motion of the nonbonded CH groups, slightly red-shifted from the nu3 band of free CH4. As n increases, additional vibrational bands appear as a result of Fermi resonances between the hydrogen-bonded CH stretching vibrational mode and the 2nu4 overtone and nu2+nu4 combination levels of the methane solvent molecules. For clusters with n < or = 8, it appears that the CH4 molecules are accommodated in the first solvation shell, each being attached to the F- anion by equivalent hydrogen bonds.

Infrared spectra of the Cl- -C2H4 and Br- -C2H4 anion dimers.

Infrared spectra of mass-selected Cl- -C2H4 and Br- -C2H4 complexes are recorded in the vicinity of the ethylene CH stretching vibrations (2700-3300 cm(-1) using vibrational predissociation spectroscopy. Spectra of both complexes exhibit 6 prominent peaks in the CH stretch region. Comparison with calculated frequencies reveal that the 4 higher frequency bands are associated with CH stretching modes of the C2H4 subunit, while the 2 weaker bands are assigned as overtone or combinations bands gaining intensity through interaction with the CH stretches. Ab initio calculations at the MP2/aug-cc-pVDZ level suggest that C2H4 preferentially forms a single linear H-bond with Cl- and Br- although a planar bifurcated configuration lies only slightly higher in energy (by 110 and 16 cm(-1), respectively). One-dimensional potential energy curves describing the in-plane intermolecular bending motion are developed which are used to determine the corresponding vibrational energies and wavefunctions. Experimental and theoretical results suggest that in their ground vibrational state the Cl- -C2H4 and Br- -C2H4 complexes are localized in the single H-bonded configuration, but that with the addition of modest amounts of internal energy, the in-plane bending wavefunction also has significant amplitude in the bifurcated structure.

Fatty acid release in incubations of serum with synaptosome and myelin subfractions of brain.

To study lipid breakdown in brain membranes following hemorrhage, synaptosome and myelin fractions isolated from rat brain were incubated with rat serum. After 3 h in vitro at 37 degrees C, 0.43 and 0.26 mumol of fatty acid were released in incubations containing synaptosomes (1.37 mumols phospholipid) or myelin (1.23 mumols phospholipid), respectively, in the presence of 0.25 mL serum. Less than 0.05 mumol of fatty acid was liberated in incubations containing only serum, synaptosomes, or myelin. For synaptosomes and serum, docosahexaenoate was the principal fatty acid released (28 mol% of total) after 3 h of incubation. This fatty acid and arachidonate made up 43 mol% of the liberated fatty acid. The presence of free docosahexaenoate was of interest, as this fatty acid is particularly enriched in phosphatidylserine and phosphatidylethanolamine, phospholipids found in the cytoplasmic half of the synaptosomal plasma membrane and in interior synaptosomal membranes. In incubations of serum and myelin, oleate was the major free fatty acid produced in 30 min to 3 h of incubation (29-35 mol% of total). After 3 h, docosahexaenoate contributed 20 mol% to the total. The release of fatty acids from the membranes may be mediated by serum phospholipase(s) or possibly by activated endogenous lipolytic activities.

The subcellular distribution of free fatty acids released during post-decapitative ischemia in rat cerebral cortex.

After periods of 5 and 30 min following decapitation, rat cerebral cortices were removed and subcellular fractions were prepared. Fractions P1A (large myelin), P1B (nuclei), P1C (cells and debris), P2A (small myelin), P2B (synaptosomes), P2C (mitochondria), and P3 (microsomes) were isolated. Free fatty acid levels of 1.0 and 1.4 mumol/g tissue were found in the homogenates at the early and late times of ischemia. In the 30-min samples, P1A, P1C, and P2A had relatively high specific contents of total free fatty acids in comparison with other subfractions. At this time P2C was relatively enriched in arachidonate, P1A and P2A were enriched in palmitate, and P2B and P3 were enriched in stearate in comparison with the homogenate. P2C had the highest ratio of polyunsaturates/saturates in its free fatty acid pool. Comparing the 5- and 30-min samples, a large increase in the quantity of free fatty acids was found in fractions P1A and P2A, so that at the later time P1A + P2A contained 60 mol% of the free fatty acid in the total subfractions derived from cerebral cortex. In comparison with the homogenate, the lack of accumulation of free fatty acids in certain membranes known to possess phospholipase activities (e.g., phospholipase A2 in P2C) and the buildup of free fatty acids in P1A and P2A led to the hypothesis that free fatty acids may be migrating outwards from intracellular sites of production and accumulating in the multilamellar structure of myelin.

The release of radioactive arachidonate from lipids of red blood cells during prolonged incubations in vitro.

Red blood cells were isolated from rat blood and incubated in the presence of [3H]arachidonate. A sizeable quantity (18%) of the radioactivity was incorporated into red cell lipids, of which phosphatidylcholine was the most highly labelled. Radioactive arachidonate was found at position 2 of this phospholipid. Free fatty acids were removed by washing the cells in solutions containing fatty-acid-free bovine serum albumin. The labelled red cells were then incubated for up to 16 h at 37 degrees C. After 16 h of incubation in saline-buffer-glucose or rat serum, 20 and 26%, respectively, of the total radioactivity was found in free fatty acids, and there were corresponding declines in the percentage radioactivities found in phosphatidylcholine. In the presence of serum, there was a more rapid release of radioactive fatty acid over the 2- to 16-h time course. There was not a significant drop in the phosphate levels of the total red cell phospholipids or phosphatidylcholine after 16 h of incubation and, as a result, there were large declines in the specific radioactivities of phosphatidylcholine. Diacylglycerols were not highly labelled and the action of phospholipase A2 on labelled phosphatidylcholine was indicated. When white blood cells were added to labelled red cells, there was little evidence of white cell involvement in the release of radioactive fatty acid, suggesting that the red cells themselves may be involved in arachidonate release. Red cells may serve as sources of arachidonate, released following hemorrhage in brain and metabolized to form various biologically active eicosanoids.

Treatment of lumbar intervertebral disc protrusions by manipulation.

From 1975 through 1983, a total of 517 patients with protruded lumbar discs were admitted for manipulative treatment. Of these, 76.8% had satisfactory results. There were 73 recurrences (14.1%) at intervals ranging from two months to 12 years. Forty-seven cases did not respond to manipulation. These results indicate that manipulation of the spine can be effective treatment for lumbar disc protrusions. In general, the manipulation consists of eight maneuvers in three positions. The selection of the appropriate maneuvers depends on the patient's symptoms and signs and on the judgment and expertise of the operator. Practice is necessary to become proficient in spinal manipulation techniques. Several mechanisms of regression lumbar disc protrusions are possible.

The release of radioactive arachidonate from lipids of red blood cell membranes: properties of membrane and serum enzymatic activities.

The release of [3H]arachidonate from the phospholipids of red blood cell membranes of rats has been studied. Membranes of red cells isolated using acid-citrate-dextrose and differential centrifugation showed an endogenous release of arachidonate at pH 7.4 in the presence of CaCl2. Membranes from red cells isolated using heparin and Percoll gradient centrifugation are better substrates for serum-mediated release of arachidonate. These experiments and results with inhibitors suggest that red blood cell and serum phospholipase A2 activities are responsible for this catabolism that may provide arachidonate for subsequent biosynthesis of eicosanoids.

Structural, dynamic, and theoretical studies of [AunPt2(PPh3)4(mu-S)2-n(mu 3-S)nL][PF6]n [n = 1, L = PPh3; n = 2, L = Ph2PCH2PPh2, (C5H4PPh2)2Fe].

Three heterometallic Au-Pt complexes [Pt2(PPh3)4(mu-S)(mu 3-S)Au(PPh3)][PF6] (2), [Pt2(PPh3)4(mu 3-S)2Au2(mu-dppm)]-[PF6]2 (3), and [Pt2(PPh3)4(mu 3-S)2Au2(mu-dppf)][PF6]2 (4) have been synthesized from Pt2(PPh3)4(mu-S)2 (1) [dppm = Ph2PCH2PPh2; dppf = (C5H4PPh2)2Fe] and characterized by single-crystal X-ray crystallography. In 2, the Au(I) atom is anchored on only one of the sulfur centers. In 3 and 4, both sulfur atoms are aurated, showing the ability of 1 to support an overhead bridge structure, viz. [Au2(P-P)], with or without the presence of Au-Au bond. The change of dppf to dppm facilitates such active interactions. Two stereoisomers of complex 3 (3a,b) have been obtained and characterized by single-crystal X-ray crystallography. NLDFT calculations on 2 show that the linear coordination mode is stabilized with respect to the trigonal planar mode by 14.0 kJ/mol. All complexes (2-4) are fluxional in solution with different mechanisms. In 2, the [Au(PPh3)] fragment switches rapidly between the two sulfur sites. Our hybrid MM-NLDFT calculations found a transition state in which the Au(I) bears an irregular trigonal planar geometry (delta G++ = 19.9 kJ/mol), as well as an intermediate in which Au(I) adopts a regular trigonal planar geometry. Complexes 3a,b are roughly diastereoisomeric and related by sigma (mirror plane) conversion. This symmetry operation can be broken down to two mutually dependent fluxional processes: (i) rapid flipping of the dppm methylene group across the molecular plane defined by the overhead bridge; (ii) rocking motion of the two Au atoms across the S...S axis of the (Pt2S2) core. Modeling of the former by molecular mechanics yields a steric barrier of 29.0 kJ/mol, close to that obtained from variable-temperature 31P(1Hz) NMR study (33.7 kJ/mol). In 4, the twisting of the ferrocenyl moiety across the S...S axis is in concert with a rocking motion of the two gold atoms. The movement of dppf is sterically most demanding, and hence, 4 is the only complex that shows a static structure at lower temperatures. Pertinent crystallographic data: (2) space group P1, a = 15.0340(5) A, b = 15.5009(5) A, c = 21.9604(7) A, alpha = 74.805(1) degrees, beta = 85.733(1) degrees, gamma = 78.553(1) degrees, R = 0.0500; (3a) space group Pna2(1), a = 32.0538(4) A, b = 16.0822(3) A, c = 18.9388(3) A, R = 0.0347; (3b) space group Pna2(1), a = 31.950(2) A, b = 16.0157(8) A, c = 18.8460(9) A, R = 0.0478; (4) space group P2(1)/c, a = 13.8668(2) A, b = 51.7754(4) A, c = 15.9660(2) A, beta = 113.786(1) degrees, R = 0.0649.