Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Cancer patterns in Jordan 1975-1979

A total of 3,604 primary malignant tumours diagnosed histologically at the Departments of Pathology in Jordan during the period 1975-1979 were analysed. The relative frequency by age, sex and site of these tumours and age-standardised incidence rate are presented. Truncated standardised incidence rates for selected tumours were compared in Jordan and other countries. Except for the urinary bladder tumours, there is a striking resemblance between Jordan and other Middle Eastern countries in the pattern of tumour-occurrence in most sites. Skin malignancies are the dominant tumours in the general and male population, breast in female population and lymphomas in children. Noteworthy are the histologically advanced bladder cancers and the relatively young females affected by breast cancer at first diagnosis. Childhood tumours comprised 7.4% of the total cancers in the present study.     

Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.     

Catheter-directed middle hemorrhoidal artery embolization for life-threatening rectal bleeding.

Over the past 10 years, arteriography has become a well-established technique for the diagnosis of acute lower gastrointestinal bleeding, but not particularly for rectal bleeding. However, to the authors' knowledge, the technique of middle hemorrhoidal artery embolization has rarely been reported in the literature. In the present report, three patients with life-threatening rectal bleeding are presented, which was controlled by superselective embolization of the middle hemorrhoidal artery or selective embolization of the internal iliac artery as a last resort.     

Impact of asthma and air pollution on school attendance of primary school children: are they at increased risk of school absenteeism?

AIM: The aim of this study was to determine the impact of asthma and air pollution on school attendance of primary school children 6 to 12 years of age in Qatar. STUDY DESIGN: This was a cross-sectional population-based study. SUBJECTS: The total 31,400 Qatari school children at the primary school (16,130 boys and 15,270 girls) 6 to 12 of age were studied to investigate school absenteeism caused by asthma and wheezing during the academic year October 2003 to July 2004. METHODS: We have used the School Health Registry for obtaining the student information and school absenteeism due to asthma and wheezing. Again we had double confirmation on the data obtained on asthmatic children by using the modified version of the International Study of Asthma and Allergies in Childhood [ISAAC] questionnaire. RESULTS: A total of 3,270 (10.4%) pupils were diagnosed as having asthma and wheezing. Overall 2,516 (8.02%) pupils were absent from the school for at least one day during the year. There was a statistically significant difference between asthmatic and wheezing students in number of days absent from the school (p < 0.0001). Most absenteeism occurred during spring for both boys (45%) and girls (47%), followed by autumn for boys (33%) and girls (36%). The measured pollutants reached a peak during the spring season and then in autumn of the studied academic year. CONCLUSION: Children with known asthma miss more days of school than those who do not have asthma. This study finding shows that air pollution has an impact on asthma, which results in significant school absenteeism.