Challenges and recommendations for magnetic hyperthermia characterization measurements.

PURPOSE: The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields - a process known as magnetic field hyperthermia (MFH) - can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating - characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg - is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. MATERIALS AND METHODS: An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing. RESULTS: The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. CONCLUSION: We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.

Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo.

Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are frequently found in several human cancer types including acute myeloid leukemia (AML) and lead to the production of high levels of the oncometabolite (R)-2-hydroxyglutarate (R-2HG). Here we report the characterization of BAY1436032, a novel pan-mutant IDH1 inhibitor, both in vitro and in vivo. BAY1436032 specifically inhibits R-2HG production and colony growth, and induces myeloid differentiation of AML cells carrying IDH1R132H, IDH1R132C, IDH1R132G, IDH1R132L and IDH1R132S mutations. In addition, the compound impacts on DNA methylation and attenuates histone hypermethylation. Oral administration of BAY1436032 led to leukemic blast clearance, myeloid differentiation, depletion of leukemic stem cells and prolonged survival in two independent patient-derived xenograft IDH1 mutant AML mouse models. Together, BAY1436032 is highly effective against all major types of IDH1 mutant AML.

Sleep disorders in Latin-American children with asthma and/or allergic rhinitis and normal controls.

BACKGROUND: Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4-10 years) from nine countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C). METHODS: Parents from 454 C children and 700 A and/or AR children followed up in allergy reference clinics completed the Children's Sleep Habits Questionnaire (CSHQ) which is a retrospective one-week questionnaire composed of 33 questions composed of seven subscales (bedtime resistance, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing and daytime sleepiness). The total scale of CSHQ and the subscales were compared between groups C and A+AR, A (n=285) vs. AR (n=390), and between controlled A (CA, n=103) vs. partially controlled/uncontrolled A (UA, n=182). RESULTS: The comparison between C and A+AR showed no significant differences in age (6.7 years vs. 7.0 years, respectively), mean Body Mass Index and total scale of CSHQ (53.3 vs. 63.2, respectively) and the subscales were significantly higher in the A+AR group. Comparison between groups A and AR, except for sleep anxiety, showed significantly higher values for CSHQ total scale (66.9 vs. 61.0, respectively) and subscales for group A. The UA group showed significantly higher values for total CSHQ scale and subscales in comparison to CA (71.1 vs. 59.4, respectively). CONCLUSIONS: Latin-American children with asthma and/or allergic rhinitis showed sleep disorders identified by the CSHQ when compared to normal controls. Despite being treated, asthma causes sleep impairment, especially when uncontrolled.

Comparative study of different carbon-supported Fe2O3-Pt catalysts for oxygen reduction reaction.

One of the challenges in electrocatalysis is the adequate dispersion of the catalyst on an appropriate porous support matrix, being up to now the most commonly used the carbon-based supports. To overcome this challenge, carbon supports must first be functionalized to guide the catalyst's nucleation, thereby, improving the dispersion and allowing the use of smaller amount of the catalyst material to achieve a higher electrochemically active surface area. This study present the effect of functionalized Vulcan carbon XC72 (FVC) and functionalized Black Pearl carbon (FBPC) as supports on the catalytic activity of decorated Fe2O3 with Pt. Both carbons were functionalized with HNO3 and subsequently treated with ethanolamine. Fe2O3 nanoparticles were synthesized by chemical reduction and decorated with platinum by epitaxial growth. Pt and Fe2O3 structural phases were identified by XRD and XPS; the Pt content was measured by XPS, and results showed to a high Pt content in Fe2O3-Pt/FBPC. TEM micrographs reveal nanoparticles with an average size of 2 nm in both supported catalysts. The Fe2O3-Pt/FVC catalyst presents the highest specific activity and mass activity, 0.21 mA cm-2Pt and 140 mA mgPt-1, respectively, associated to the appropriate distribution of platinum on the Fe2O3 nanoparticles.

Sleep-related disorders in Latin-American children with atopic dermatitis: A case control study.

BACKGROUND: Atopic dermatitis (AD) has been associated with impairment of sleep. The aim of this study was to evaluate sleep disorders in AD Latin-American children (4-10 years) from nine countries, and in normal controls (C). METHODS: Parents from 454 C and 340 AD children from referral clinics answered the Children Sleep Habits Questionnaire (CSHQ), a one-week retrospective 33 questions survey under seven items (bedtime resistance, sleep duration, sleep anxiety, night awakening, parasomnias, sleep-disordered breathing and daytime sleepiness). Total CSHQ score and items were analysed in both C and AD groups. Spearman's correlation coefficient between SCORAD (Scoring atopic dermatitis), all subscales and total CSHQ were also obtained. RESULTS: C and AD groups were similar regarding age, however, significantly higher values for total CSHQ (62.2±16.1 vs 53.3±12.7, respectively) and items were observed among AD children in comparison to C, and they were higher among those with moderate (54.8%) or severe (4.3%) AD. Except for sleep duration (r=-0.02, p=0.698), there was a significant Spearman's correlation index for bedtime resistance (0.24, p<0.0001), sleep anxiety (0.29, p<0.0001), night awakening (0.36, p<0.0001), parasomnias (0.54, p<0.0001), sleep-disordered breathing (0.42, p<0.0001), daytime sleepiness (0.26, p<0.0001) and total CSHQ (0.46, p<0.0001). AD patients had significantly higher elevated body mass index. CONCLUSION: Latin-American children with AD have sleep disorders despite treatment, and those with moderate to severe forms had marked changes in CSHQ.

Enantiomer-specific and paracrine leukemogenicity of mutant IDH metabolite 2-hydroxyglutarate.

Canonical mutations in IDH1 and IDH2 produce high levels of the R-enantiomer of 2-hydroxyglutarate (R-2HG), which is a competitive inhibitor of α-ketoglutarate (αKG)-dependent enzymes and a putative oncometabolite. Mutant IDH1 collaborates with HoxA9 to induce monocytic leukemia in vivo. We used two mouse models and a patient-derived acute myeloid leukemia xenotransplantation (PDX) model to evaluate the in vivo transforming potential of R-2HG, S-2HG and αKG independent of the mutant IDH1 protein. We show that R-2HG, but not S-2HG or αKG, is an oncometabolite in vivo that does not require the mutant IDH1 protein to induce hyperleukocytosis and to accelerate the onset of murine and human leukemia. Thus, circulating R-2HG acts in a paracrine manner and can drive the expansion of many different leukemic and preleukemic clones that may express wild-type IDH1, and therefore can be a driver of clonal evolution and diversity. In addition, we show that the mutant IDH1 protein is a stronger oncogene than R-2HG alone when comparable intracellular R-2HG levels are achieved. We therefore propose R-2HG-independent oncogenic functions of mutant IDH1 that may need to be targeted in addition to R-2HG production to exploit the full therapeutic potential of IDH1 inhibition.

Synthesis and characterization of magnetoliposomes for MRI contrast enhancement.

This work assesses the characteristics of magnetoliposomes of soybean phosphatidylcholine (SPC):cholesterol (Chol) loaded with superparamagnetic iron oxide nanoparticles (IONPs) stabilized with tetramethylammonium hydroxide (TMAOH) and their capacity to enhance magnetic resonance imaging (MRI) contrast. Magnetoliposomes of SPC were used for comparative studies. IONPs and magnetoliposomes were characterized using transmission electron microscopy, dynamic light scattering, SQUID magnetometry, FTIR and MRI. The saturation magnetization at 10K was ~0.06 Am(2)/kg for SPC:Chol magnetoliposomes with 7 g iron oxide/mol of lipid and ~0.05 Am(2)/kg for SPC magnetoliposomes with 21 g iron oxide/mol of lipid. As these values are associated with the number of incorporated magnetic IONPs, the saturation magnetization is 1.2 times higher for magnetoliposomes of SPC:Chol as compared with magnetoliposomes of SPC alone. The behavior of temperature dependence in both cases is typical of superparamagnetic particles. FTIR spectra evidence the increase of magnetoliposome membrane ordering with the presence of Chol. Principal component analysis (PCA) applied to FTIR spectra evidenced a clear distinction between scores for SPC:Chol, and SPC magnetoliposomes and for SPC empty liposomes. PCA applied to FTIR data differentiate magnetoliposomes from empty liposomes. MR images of aqueous phantoms obtained with and without magnetoliposomes, clearly evidence their effect on T2 image weighting.

Nitrogen and argon doped zinc oxide.

In this work argon and nitrogen were implanted into ZnO single crystals in order to compare the influence of these non-magnetic elements in the magnetic and electrical behaviour of zinc oxide. The results indicate that both nitrogen and argon implantations induce magnetic defects in ZnO, although these do not remain stable upon annealing. The comparison between the electrical behaviour of argon and nitrogen implanted crystals indicates that mobile charge carriers exist in the argon implanted sample after annealing, but were not detected in the nitrogen implanted sample.

Ferromagnetism induced in rutile single crystals by argon and nitrogen implantation.

The magnetic properties of Ar- and N-implanted single crystalline TiO(2) rutile were studied and correlated with the induced disorder in order to clarify the influence of defects in the magnetic behaviour. Nominal fluences of 1 × 10(17) and 2 × 10(17) cm(-2) and an implantation energy of 100 keV were used. The as-implanted single crystals exhibited ferromagnetic behaviour up to 380 K. Annealing at 1073 K induced recovery of the lattice structure and the decrease of the ferromagnetic moment in the case of Ar-implanted samples, but the magnetic moment did not change significantly for the samples implanted with nitrogen. No impurities, other than the implanted species were detected and consequently the ferromagnetic behaviour is attributed to defects created during implantation, which in the case of nitrogen remained in the lattice even after partial recovery of the structure.

[A clinical case of chronic thrombotic thrombocytopenic purpura]. / A propósito de um caso clínico de purpura trombótica trombocitopénica crónica.

This is a TTP report of the case of a 29 year old female who entered into apparent complete clinical remission, after EP with fresh frozen plasma and corticotherapy. Unusual large plasma Factor VIII: vWF by two-dimensional Immunoelectrophoresis is the biological change described by Moake and Sufficient in itself to confirm the chronic TTP diagnosis.

Effect of posture and physical activity on urinary protein excretion by patients with glomerular proteinuria diseases

The rate of urinary protein excretion (Uprot.V) was evaluated in 20 patients with massive proteinuria caused by various histopathological types of glomerular disease. Measurements were made during five consecutive periods: period A (overnight bed res) and periods B, C, D and E corresponding to normal everyday upright physical activity. Mean Uprot.V was significantly lower during period A (8.2 + or - 1.3 mg/min, mean + or - SEM) than during all the periods of physical activity (11.8 + or - 1.8 mg/min). For 5/20 patients, physical activity induced a mean percent increase of 340 + or - 200% and for 11 an increase of 51 + or - 7% was observed. Only in 4 patients was the rate of urinary protein excretion unaffected or decreased on the average by -20 + or - 9% during physical activity

Hinged cast and roller traction for fractured femur. A system of treatment for the Third World.

Hinged casts and roller traction were used in two developing countries to treat fractured femora, most of which were due to road traffic accidents or civil violence. This method of treatment, developed by Neufeld, is particularly useful in the Third World because it uses local materials, adapted in a hospital workshop, and circumvents the difficulties and complications of standard traction and of operative treatment. The results are reported from 11 patients treated in Uganda in 1979 and from 110 treated in the Dominican Republic in 1981 and 1982. All but one fracture united without complication or significant shortening after a brief period in hospital. The method was easily taught to hospital staff and is strongly recommended.

Contribuicoes ao emprego da cirurgia ambulatorial em pediatria. / Use of the ambulatorial surgery in pediatrics

Os autores apresentam algumas modificacoes empregadas no metodo de cirurgia ambulatorial em pediatria, com enfase na simplificacao e seguranca, chamando atencao para os principios basicos na sua implantacao e manuntencao