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This study reports the effects of a high-fat (HF) diet on the iron (Fe) status of growing rats over 8 weeks. Tissue Fe levels were analysed by atomic absorption spectrophotometry, and whole-body adiposity was measured by dual-energy X-ray absorptiometry. Histopathology and morphometry of adipose tissue were performed. Liver homogenates were used for measuring ferroportin (Fpn)-1 protein levels by immunoblotting, and transcript levels were used for Fe genes measured by real-time PCR. Tissue Fe pools were fit to a compartmental biokinetic model in which Fe was assessed using 14 compartments and 27 transfer constants (kj,i from tissue “i” to tissue “j”) adapted from the International Commission on Radiological Protection (ICRP) 69. Ten kj,i were calculated from the experimental data using nonlinear regression, and 17 were estimated by allometry according to the formula kj,i = a · Mb. Validation of the model was carried out by comparing predicted and analysed Fe pool sizes in red blood cells (RBCs), the liver and the spleen. Body adiposity was negatively associated with serum Fe levels and positively associated with liver Fe stores. An inferred increase in Fe transfer from bone marrow to the liver paralleled higher hepatic Fe concentrations and ferritin heavy-chain mRNA levels in the HF diet-fed animals, suggesting that liver Fe accumulation occurred at least in part due to a favoured liver RBC uptake. If this feeding condition were to be prolonged, impaired Fe decompartmentalization may occur, ultimately resulting in dysmetabolic Fe overload.
The purpose of this study was to evaluate the dosimetric impact of multileaf collimator (MLC) positional errors on dynamic intensity-modulated radiotherapy (IMRT) treatments through planning simulation. Secondly the sensitivity of IMRT MatriXX device for detecting the MLC leaf positional errors was also evaluated.
Materials and methods
In this study five dynamic IMRT plans, each for brain and head–neck (HN), were retrospectively included. An in-house software was used to introduce random errors (uniform distribution between −2·0 and +2·0 mm) and systematic errors [±0·5, ±0·75, ±1·0 and ±2·0 mm (+: open MLC error and −: close MLC error)]. The error-introduced MLC files were imported into the treatment planning system and new dose distributions were calculated. Furthermore, the dose–volume histogram files of all plans were exported to in-house software for equivalent uniform dose (EUD), tumour control probability and normal tissue complication probability calculations. The error-introduced plans were also delivered on LINAC, and the planar fluences were measured by IMRT MatriXX. Further, 3%/3 mm and 2%/2 mm γ-criteria were used for analysis.
In planning simulation study, the impact of random errors was negligible and ΔEUD was <0·5±0·7%, for both brain and HN. The impact of systematic errors was substantial, and on average, the maximum change in EUD for systematic errors (close 2 mm) was −10·7±3·1% for brain and −15·5±2·6% for HN.
It can be concluded that the acceptable systematic error was 0·4 mm for brain and 0·3 mm for HN. Furthermore, IMRT MatriXX device was able to detect the MLC errors ≥2 mm in HN and >3 mm errors in brain with 2%/2 mm γ-criteria.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
The aim of this review is to compare the performance of different reproductive programs using natural service, estrus synchronization treatment before natural service (timed natural breeding (TNB)), artificial insemination (AI) following estrus detection and timed artificial insemination (TAI) in beef herds. It is well known that after parturition the beef cow undergoes a period of anestrous, when they do not exhibit estrus, eliminating the opportunity to become pregnant in the early postpartum by natural mating or by AI after detection of estrus. Hormonal stimulation is already a consistent and well-proven strategy used to overcome postpartum anestrus in beef herds. Basically, hormones that normally are produced during the estrous cycle of the cow can be administered in physiological doses to induce cyclicity and to precisely synchronize follicular growth, estrus and ovulation. Furthermore, two options of mating may be used after hormonal stimulation: natural service (i.e. utilization of bull service after synchronization, referred to as TNB) and TAI. These strategies improve the reproductive efficiency of the herds compared with natural service without estrus induction or synchronization. After the first synchronized service, the most common strategy adopted to get non-pregnant cows pregnant soon is the introduction of clean-up bulls until the end of the breeding season. However, methods to resynchronize non-pregnant cows after the first service are already well established and offer a potential tool to reduce the time for subsequent inseminations. Thus, the use of these technologies enable to eliminate the use of bulls by using resynchronization programs (i.e. two, three or four sequential TAI procedures). The dissemination of efficient reproductive procedures, such as TNB, TAI and Resynch programs, either isolated or in combination, enables the production of a greater quantity (obtaining increased pregnancy rates early in the breeding season) and quality (maximization of the use of AI with superior genetic sires) of beef calves. These technologies can contribute to improve the production efficiency, and consequently, improve livestock profitability.
Background: The Gilenya® Go ProgramTM offers education and support services, including coordination of first dose observation (FDO) and follow-up contact to reinforce monitoring recommendations and compliance in fingolimod-treated relapsing-remitting multiple sclerosis (RRMS) patients. Methods: Data were analyzed for patients enrolled in the Canadian Gilenya® Go ProgramTM from March 2011 to January 2016. The retention to fingolimod therapy, reasons for treatment discontinuation and incidence of adverse events (AEs) during treatment are reported. Results: At data cut-off, 3956 patients had completed FDO; 3201 patients were being actively treated. Mean age at enrolment was 41.0 years; 74.9% patients were female. The overall fingolimod exposure was 7869 patient-years. Most recent previous therapies (n=3746) included interferons (43.3%) and glatiramer acetate (29.6%). Most common reasons for switching to fingolimod (n=3674) was lack of efficacy (31.8%). Retention to therapy at data cut-off was 81.3%. AEs (45.2%) were the most common reason (n=334) for treatment discontinuation and included low lymphocyte count/abnormal hematology values (13.8%), gastrointestinal disturbances (6.9%), and elevated liver enzyme levels (7.8%). Adherence to recommended ophthalmic examination was 92.4%. Conclusions: In real-world clinical practice in Canada, adherence to both fingolimod treatment and monitoring was high. The Gilenya® Go Program™ helps to meet the safety monitoring recommendations for fingolimod-treated RRMS patients.
Background: Traditional neurosurgical techniques and/or stereotactic radiotherapy, although effective for solid tumors, can be associated with high morbidity and be relatively ineffective for long-term control of cystic sellar/parasellar tumors. The rationale of our study was to examine the efficacy and safety of stereotactic intracavitary instillation of 90yttrium colloid for the primary treatment of cystic tumors. Methods: As part of a Health Canada approved clinical trial, we have enrolled nine patients (6 females, 3 males; mean age 64, range 43 to 83 years) for treatment of symptomatic and/or enlarging cysts. Ten cystic sellar/parasellar lesions underwent right frontal stereotactic insertion of 90yttrium colloid to deliver a radiation dose of 200 Gy to the cyst wall. Results: Compared with pre-treatment cyst volumes (mean 4.6 cc; range 0.8-16.1 cc), the cysts decreased in size at 3 months (2.6 cc; 0.2-10 cc) with further shrinkage (n=5) at 9 months (1 cc; 0.1-2.7 cc). Of 9 patients with pre-operation visual field defects, 6 showed improvement. The single complication was a delayed (1 month) incomplete CNIII palsy. Conclusions: Our early experience indicates that 90yttrium colloid delivered to a cystic craniopharyngioma provides an efficacious alternative to open surgery for primary treatment of these cystic lesions.
The SoHO/MDI experiment generates a continous record of the solar limb brightness using 1.96″ pixels. Because there is no atmospheric blurring, these data allow measurements of solar limb brightness and shape changes with a precision that has not been achieved from the ground. The first results of a 1 month astrometric timeseries from the MDI solar structure program will be described here.
The unprecedented combination of spatial resolution and stability achieved by the Solar Oscillations Investigation/Michelson Doppler Imager on SOHO has opened up new opportunities for the analysis of solar surface oscillations of high spatial frequencies. In this regime the oscillations are essentially plane waves, amenable to the techniques of ring-diagram analysis of their three-dimensional power spectra. This approach holds the promise of measuring fluid motions and possibly magnetic fields in spatially-resolved structures within the uppermost levels of the convective envelope, a region unresolved by the global modes. Atmospheric g-modes trapped above the photosphere may also be detectable. We review the first results of plane-wave analysis of various types of SOI data and comparisons with the analyses of comparable ground-based datasets.
Haemonchus contortus is one of the major gastrointestinal nematodes responsible for significant economic and production losses of sheep. Diseases caused by this species lack effective anthelmintic products, and the search for new compounds to replace synthetic anthelmintics has been extensive. The present investigation assesses the in vitro activity of the essential oil of melaleuca (Melaleuca alternifolia), both free (TTO) and nanostructured (nanoTTO), and terpinen-4-ol (terp-4-ol) on eggs and larvae of H. contortus. Tests of egg hatching (EHT) and inhibition of larval migration (LMIT) were used to assess the in vitro efficacy of TTO, nanoTTO and terp-4-ol. Using EHT, at a concentration of 3.5 mg/ml, 100% inhibition occurred using TTO and terp-4-ol, with LC50 values of 0.43 and 0.63 mg/ml, and LC90 values of 1.75 mg/ml and 3.12 mg/ml, respectively. NanoTTO had lower activity, with 82.6% inhibition at the same concentration. Using LMIT, TTO and nanoTTO had a similar activity with 88.0% and 84.8% inhibition, respectively, at a concentration of 56 mg/ml. Terp-4-ol had a greater effect on larvae, with 85.7% inhibition at a concentration of 56 mg/ml and 82.4% at 3.5 mg/ml, demonstrating high activity at the lowest concentration tested. Therefore, the results indicate that all substances tested showed ovicidal and larvicidal activity against H. contortus. TTO, terp-4-ol and, mainly, nanoTTO may be targeted in in vivo studies, besides being a promising line of research into the control and treatment of veterinary important helminths.
Using the polymerase chain reaction (PCR) test for diagnosis of canine leishmaniasis has greater sensitivity and specificity than culture and visualization of the parasite. This study compares PCR for the diagnosis of the genus and species of Leishmania with serological techniques used for the control of canine visceral leishmaniasis (CVL) in Brazil, considering two regions. We analysed peripheral blood samples collected from 195 dogs in the Campinas (SP) and Teresina (PI) regions. ELISA was performed as a serological method and PCR was performed using specific primers for the genus Leishmania spp. and the species Leishmania chagasi. In Campinas, a greater sensitivity of PCR (88·24%) (P = 0·0455) compared to Teresina (14·71%) (P < 0·0001) was observed, and an agreement was observed for Cohen's kappa index (0·9096). Both PCR and ELISA showed discordance for sensitivity (Campinas 100%, Teresina 21·74%), specificity (Campinas 30·77%, Teresina 100%), positive predictive value (Campinas 68·97%, Teresina 100%), negative predictive value (Campinas 100%, Teresina 37·94%) and Cohen's kappa index (0·1238). This study confirms the importance of PCR in analysis of the canine reservoir, and as an effective method for the detection of active and recent infection.
The effect of the initial nitridation of the sapphire substrate on the GaN crystal quality as a function of substrate temperature was studied. GaN layers were grown by plasma-assisted molecular beam epitaxy (MBE) on sapphire substrates nitridated at different substrate temperatures. A strong improvement in the GaN crystal quality was observed at 100 °C nitridation temperature. Symmetric (0004) and asymmetric (10-5) full widths at half maximum (FWHM) of the x-ray rocking curves were 136 and 261 arcsec, respectively. This compares to an x-ray rocking curve full width at half maximum of 818 arcsec (0004) for conventional MBE buffer conditions. For our conventional buffer conditions, sapphire substrates were exposed to a N plasma at temperatures above 500 °C for 10min and then 25~50nm buffers were deposited without annealing at high temperature. The low temperature nitridation also shows an enhancement of the lateral growth of the GaN, resulting in larger grain sizes. The largest grain size achieved was approximately 2.8μm, while the average grain size was approximately 2.4μm at 100 °C nitridation temperature.
Exposure to lead may cause changes in the male reproductive system. We evaluated the effect of lead chloride (PbCl2) in vitro on semen quality from 31 individuals. Samples were incubated at room temperature for two exposure times (4 h and 8 h) and with two concentrations of PbCl2 (15 μg/ml or 30 μg/ml). Results showed that PbCl2 significantly inhibited rapid progressive motility and caused an increase in the percentage of tail anomalies in both times and concentrations assessed, as well as a decrease in vitality in the group exposed to 30 μg/ml PbCl2. A significant increase in immotile sperm was also observed between the group control and the groups submitted to lead. Total motility and DNA fragmentation also showed a significant decrease and increase, respectively, after 4 h of incubation in the group exposed to 30 μg/ml and in both groups after 8 h of incubation. In conclusion, PbCl2 affected sperm parameters and DNA integrity, which are essential for male fertility.
Human oocyte dysmorphisms attain a large proportion of retrieved oocytes from assisted reproductive technology (ART) treatment cycles. Extracytoplasmic defects involve abnormal morphology of the zona pellucida (ZP), perivitelline space and first polar body. The aim of the present study was to describe a novel dysmorphism affecting the ZP, indented ZP. We also evaluated the clinical, embryological and ultrastructural features of these cases. We evaluated all ART treatment cycles during 7 consecutive years and found 13 treatment cycles (six patients) with all oocytes presenting an indented ZP. In addition, these oocytes presented total or partial absence of the perivitelline space, absence of resistance to ZP and oolemma penetration during microinjection, and low ooplasm viscosity during aspiration. This novel described dysmorphism was recurrent and attained all oocytes in three cases that had more than one treatment cycle. When compared with controls, data showed significant low oocyte maturity (42% versus 81.6%) and high cycle cancellation (30.8% versus 8.5%) rates, normal degeneration (3.4% versus 6.3%) and fertilization rates (69% versus 69.5%), and low pregnancy (15.4% versus 33.3%) and live-birth delivery (7.7% versus 27.7%) rates per cycle. Ultrastructure analysis revealed a zona pellucida structure with large empty electrolucent regions, an outer ZP layer with an indented surface with protuberances and a thick inner ZP that obliterated the perivitelline space. There was evidence of exocytosis of ZP material by the oocyte. In conclusion, oocytes with this novel described dysmorphism (indented ZP) are associated with low maturity, pregnancy and live-birth delivery rates.
Increasing research effort is being dedicated to investigating the links between emotional processes and psychosis, despite the traditional demarcation between the two. Particular focus has alighted upon two specific anxious and depressive processes, worry and rumination, given the potential for links with aspects of delusions and auditory hallucinations. This study rigorously explored the nature of these links in the context of the daily life of people currently experiencing psychosis.
Experience sampling methodology (ESM) was used to assess the momentary links between worry and rumination on the one hand, and persecutory delusional ideation and auditory hallucinations on the other. Twenty-seven participants completed the 6-day experience sampling period, which required repeated self-reports on thought processes and experiences. Multilevel modelling was used to examine the links within the clustered data.
We found that antecedent worry and rumination predicted delusional and hallucinatory experience, and the distress they elicited. Using interaction terms, we have shown that the links with momentary symptom severity were moderated by participants' trait beliefs about worry/rumination, such that they were reduced when negative beliefs about worry/rumination (meta-cognitions) were high.
The current findings offer an ecologically valid insight into the influence of worry and rumination on the experience of psychotic symptoms, and highlight possible avenues for future intervention strategies.
The structure and dynamics of young stellar object (YSO) accretion shocks depend strongly on the local magnetic field strength and configuration, as well as on the radiative transfer effects responsible for the energy losses. We present the first 3D YSO shock simulations of the interior of the stream, assuming a uniform background magnetic field, a clumpy infalling gas, and an acoustic energy flux flowing at the base of the chromosphere. We study the dynamical evolution and the post-shock structure as a function of the plasma-beta (thermal pressure over magnetic pressure). We find that a strong magnetic field (~hundreds of Gauss) leads to the formation of fibrils in the shocked gas due to the plasma confinement within flux tubes. The corresponding emission is smooth and fully distinguishable from the case of a weak magnetic field (~tenths of Gauss) where the hot slab demonstrates chaotic motion and oscillates periodically.
A Message Authentication Code (MAC) is a function that takes a message and a key as
parameters and outputs an authentication of the message. MAC are used to guarantee the
legitimacy of messages exchanged through a network, since generating a correct
authentication requires the knowledge of the key defined secretly by trusted parties.
However, an attacker with access to a sufficiently large number of message/authentication
pairs may use a brute force algorithm to infer the secret key: from a set containing
initially all possible key candidates, subsequently remove those that yield an incorrect
authentication, proceeding this way for each intercepted message/authentication pair until
a single key remains. In this paper, we determine an exact formula for the expected number
of message/authentication pairs that must be used before such form of attack is
successful, along with an asymptotical bound that is both simple and tight. We conclude by
illustrating a modern application where this bound comes in handy, namely the estimation
of security levels in reflection-based verification of software integrity.
Spermatogenesis is a complex process of cell proliferation, meiosis and differentiation. In order to determine the genetic mechanisms that control this process we need to develop adequate methodologies for the purification of stage-specific germ cells. In this study we aim to evaluate four markers (c-kit, oct-4, Integrin α6 and Integrin β1), used to isolate spermatogonial stem cells in mammals, as possible markers to isolate/sort testicular adult stem and progenitor cells in humans.