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.     

Identification of antibacterial principles against Streptococcus mutans and inhibitory principles against glucosyltransferase from the seed of Areca catechu L

During the course of our studies on dental caries prevention by traditional medicines, fatty acids (myristic and oleic acids etc.) and procyanidins from betel nuts (the seed of Areca catechu L.) were respectively revealed to be the major antibacterial principles against a primary cariogenic bacterium, Streptococcus mutans, and the major inhibitory principles against glucosyltransferase from S. mutans.     

A reusable, custom-made warming blanket prevents core hypothermia during major neonatal surgery

PURPOSE: To introduce a reusable model of neonatal forced air warming blanket for intraoperative use during major noncardiac neonatal surgery and to determine clinical efficacy of this reusable blanket compared with the commonly used disposable blankets. METHODS: Delivered air temperature and calorie uptake of standard thermal bodies within the reusable blankets, Bair Hugger(R) blanket model 530 and model 555 were studied. Also, an efficacy study was conducted in 90 neonatal patients scheduled for major noncardiac surgery comparing the reusable blanket, the Bair Hugger(R) blanket model 530 and passive heat conservation as a control. The covered reusable blanket was used as a rescue procedure if the core temperature was < 35.5 degrees C. RESULTS: Delivered air temperature and heat transfer from the covered reusable blanket did not differ significantly from those of the Bair Hugger(R) blanket model 530 and model 555 (despite 0.75 degrees C-1.2 degrees C of heat trapped under the sheet and 1.3 Kcal less energy transfer). Temperatures measured underneath patients (correlated to poorly perfused areas) were highest using the Bair Hugger(R) blanket model 555. The reusable blanket was efficacious in preventing intraoperative core hypothermia and not different from the Bair Hugger(R) blanket model 530. About 1/3 of the patients in the control group had presented a core temperature < 35.5 degrees C but were successfully rescued using the reusable blanket. No adverse events were associated with any of these warming methods. CONCLUSION: This study shows the clinical efficacy of our reusable blanket for the prevention of core hypothermia during major neonatal surgery, which is not different from commonly used disposable blankets.     

Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample

Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096-1103].     

In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens

Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.     

Complications After Surgical Treatment of Geriatric Ankle Fractures

The incidence of geriatric ankle fractures is rising and the potential for complications is high in this population. Little is known about factors associated with increased postoperative complications after surgical fixation of ankle fractures in older-age patients. The purpose of this retrospective cohort study was to assess the epidemiology and risk factors for complications after surgically treated ankle fractures in geriatric patients. All patients who were 65 years or older and had a surgically treated ankle fracture were included. Pilon fractures, patients who were initially treated conservatively or who had less than 1 month of follow-up were excluded. Postoperative complications, demographic-, fracture- and surgical data of 282 patients were recorded from two level 2 trauma centers between 2012 and 2017. A total of 87 (30.9%) patients developed a complication, of which wound related complications were most frequently reported. Superficial and deep wound infections were observed in 27 (9.6%) and 18 (6.4%) patients, respectively. Multivariate regression analysis demonstrated increased age to be an independent predictive variable for the occurrence of postoperative complications (odds ratio 1.04; 95% confidence interval 1.00-1.09), while cast immobilization for more than 2 weeks was a protective factor for the development of wound related complications (odds ratio 0.34; 95% confidence interval 0.17-0.66). In conclusion, the incidence of postoperative complications among geriatric patients after surgical treatment of ankle fractures is high and patients should be informed accordingly.     

The effects of feeding an Asian or Western diet on sperm numbers, sperm quality and serum hormone levels in cynomolgus monkeys (Macaca fascicularis) injected with testosterone enanthate (TE) plus depot medroxyprogesterone acetate (DMPA)

The aim of this study was to elucidate the effects of an Asian diet compared to a Western diet on sperm numbers and quality, and serum hormones in cynomolgus monkeys (Macaca fascicularis) injected with testosterone enanthate (TE) plus depot medroxyprogesterone acetate (DMPA). Thirty male monkeys were divided into three groups of ten animals each. The first group (control) was fed with standard diet 'monkey chow' (9% fat, 13% protein, 78% carbohydrate); the second group was fed an 'asian' diet (15% fat, 15% protein, 70% carbohydrate); the third group was fed a 'Western' diet (35% fat, 25% protein, 40% carbohydrate). These diets were administered from the beginning (adaptation) until the experiment was terminated. Three months after the adaptation period, all groups were injected with 20 mg TE (once per week) and 25 mg DMPA (once every 6 weeks) for 18 weeks, while TE injections were continued for another 6 weeks. There were no differences in sperm numbers and quality, or in hormone levels between the first and second groups. In both of these groups azoospermia was achieved in 100% of animals, while in the third group only 70% achieved azoospermia. In all 3 groups, spermatozoa were once again detectable by week 33. However, by the end of the study at week 39, sperm numbers in the first and second groups reached only severe oligozoospermia (two animals remained azoospermic in the first group) while in the third group, numbers had returned to normozoospermia. The quality of spermatozoa during and after the treatment in the third group was better than in the first and second groups. Hormone concentrations decreased more rapidly in both the first and second groups, compared to the third group, while the recovery period was slower in the first and second groups, compared to the third group. It is concluded that different formula diets result in differential decreases in sperm numbers and quality, and in hormone concentrations in M. fascicularis injected with TE in combination with DMPA. Animals fed with either monkey chow or an Asian diet exhibited more severe and prolonged decreases in these parameters than did animals fed with a Western diet.     

Hepatoprotective effect of Pandanus odoratissimus seed extracts on paracetamol-induced rats

ContextPandanus odoratissimus Linn. (Pandanaceae) seed extract is known to have antioxidant activities. However, the potential hepatoprotective effect is still unclear.ObjectiveTo investigate the hepatoprotection aspect of P. odoratissimus methanol extract towards paracetamol-induced rats.Materials and methodsThirty male Sprague–Dawley rats were randomly divided into six equal groups: one group served as the healthy control and five groups with hepatotoxicity (hepatotoxic control and 4 treatment groups). The oral treatment of paracetamol-induced hepatotoxicity of 3 g/kg using three different concentrations of P. odoratissimus (300, 600 and 900 mg/kg), and silymarin (200 mg/kg) groups were administered once a day for 14 days. Enzyme activities and protein levels in serum were determined in rats at the end of the treatments. The histopathology of rat livers was observed under an electron microscope with 10× magnification.ResultsPandanus odoratissimus significantly decreased the serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) activities in induced-paracetamol rat serum (p < 0.05). Moreover, P. odoratissimus significantly decreased total bilirubin and direct bilirubin levels (p < 0.05). It significantly blocked the decline of serum albumin and protein levels (p < 0.05). Histopathological changes amplified paracetamol-induced liver damage and the hepatoprotective effect of P. odoratissimus in the liver.Discussion and conclusionsPandanus odoratissimus improved the hepatoprotective effect in a concentration-dependent manner by reducing related hepatic enzyme and protein markers, suggesting as a useful agent in hepatotoxicity treatment, and it can be generalized to a broader study population in different hepatotoxic animal models.