Non-Invasive Radiofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma

Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed

CHEMOSENSITIZATION OF HEPATOCELLULAR CARCINOMA TO GEMCITABINE BY NON-INVASIVE RADIOFREQUENCY FIELD-INDUCED HYPERTHERMIA

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage through late S/ G2 phase of cell cycle in comparison to cells treated with gemcitabine alone. This coincides with inhibition of resolution of γH2AX foci. Our findings also demonstrate that thermal sensitization of human hepatocellular carcinoma cell lines to gemcitabine is mediated through an Mre11-dependent homologous recombination repair pathway. Combination of non-invasive radiofrequency field-induced hyperthermia and gemcitabine was superior to either therapy alone (

Gold nanoparticles and radiofrequency in experimental models for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal and chemo-refractory cancers, clearly, alternative treatment strategies are needed. We utilized 10 nm gold nanoparticles as a scaffold to synthesize nanoconjugates bearing a targeting antibody (cetuximab, C225) and gemcitabine. Loading efficiency of gemcitabine on the gold nanoconjugates was 30%. Targeted gold nanoconjugates in combination with RF were selectively cytotoxic to EGFR expressing Hep3B and SNU449 cells when compared to isotype particles with/without RF (P < 0.05). In animal experiments, targeted gold nanoconjugates halted the growth of subcutaneous Hep3B xenografts in combination with RF exposure (P < 0.05). These xenografts also demonstrated increased apoptosis, necrosis and decreased proliferation compared to controls. Normal tissues were unharmed. We have demonstrated that non-invasive RF-induced hyperthermia when combined with targeted delivery of gemcitabine is more effective and safe at dosages ~ 275-fold lower than the current clinically-delivered systemic dose of gemcitabine

Depression and Anxiety among Patients with Epilepsy and Multiple Sclerosis: UAE Comparative Study

Depression and anxiety are highly prevalent in patients with epilepsy (PWE), with prevalence rates ranging from 20% to 55%. The cause of this increased rate is multifactorial. Depression and epilepsy are thought to share the same pathogenic mechanism. Anxiety, on the other hand, seems to have a prevalence rate among PWE comparable to, or even higher than, those reported for depression, and it is closely linked to epilepsy. To test this hypothesis, we screened for depression and anxiety 186 and 160 patients attending the epilepsy and MS clinics, respectively, using standardized screening tools to determine the rates of both depression and anxiety, comparing these rates to 186 age, sex matched controls. Among the three groups, only patients with epilepsy were at increased risk of having depression (OR = 1.9), whereas anxiety was not. This finding could point to the shared pathogenic mechanisms hypothesis between depression and epilepsy

Enhancement of electrochemical activity of Raney-type NiZn coatings by modifying with PtRu binary deposits: Application for alkaline water electrolysis

This study presents electrochemical preparation and characterization of PtRu-modified Cu/Ni/NiZn electrodes (Cu/Ni/NiZn-PtRu) as cathode materials for alkaline water electrolysis. The electrodes were characterized using energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. Their electrochemical activities as cathode materials for alkaline water electrolysis were evaluated with the help of current potential curves. The results showed that the PtRu-modified layers have porous structures with relatively low Pt and Ru chemical compositions. The modification of the alkaline leached Cu/Ni/NiZn surface by Pt and/or Ru enhances the electrochemical activity of the electrode. Their catalytic activity depends on the molar ratios of Pt and Ru; the PtRu binary deposit with the percentage weight ratio of approximately 56:44 exhibits the highest hydrogen evolution activity among the studied electrodes. The enhanced hydrogen evolution activity of the PtRu-modified electrodes was related to the porous surface and/or a possible synergistic effect between the metals. Copyright (c) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

Awareness and Use of Benzodiazepines in Healthy Volunteers and Ambulatory Patients Visiting a Tertiary Care Hospital: A Cross Sectional Survey

Background: Indiscriminate prescription of Benzodiazepines in Pakistan and subsequent availability over-the-counter without prescription is a major public health problem, requiring systematic inquiry through research. Additionally, there is limited data on the awareness and use of Benzodiazepines from developing countries making it impossible to devise meaningful health policies. Methodology/Principal Findings: This was an Observational, Cross-Sectional study. conducted at Aga Khan University. A total of 475 (58.5 % males, 41.5 % females) people visiting a tertiary care hospital were interviewed by means of a structured questionnaire. The results showed that majority of population was aware of one or more Benzodiazepines (80.4%) and 30.4 % had used them at some point in life. 42.4 % of the users had been using it for more than a year. Commonest reason for use was sleep disturbance. Frequency of usage was higher for females, married individuals, educated (.Grade12), high socioeconomic status and housewives. More (59%) were prescribed than not and of them most by GP (58.5%). Only 36.5% of them were particularly told about the long-term addiction potential by the use of these drugs. Conclusion: Easy availability, access to re-fills without prescription and self prescription compounded with the lack of understanding of abuse potential of benzodiazepines constitutes a significant problem demanding serious consideratio

Long term effects of gastric bypass on quality of life and bone mineral density

Obesity is a worldwide disease. Surgery is currently the only available management option which offers an adequate long-term effect on comorbidity, quality-of-life and weight loss. It is evident that overweight and obesity are associated with low health-related quality-of life (HRQoL) and multiple comorbidities. The aim of this thesis has been to explore the long-term effect of gastric bypass surgery on HRQoL and bone mineral density. In study 1: 486 patients (average age 50.7±10.0 years, 84 % female) operated with gastric bypass (GBP) from 1993 to 2003 at the University Hospitals of Örebro and Uppsala. Mean follow-up after GBP was 11.5±2.7 years (range 7–17). The study group was compared with two control groups. The study group scored better in the SF-36 domains and OP scale compared to obese controls, but their HRQoL scores were lower than those of the general population. HRQoL was better among younger patients and in the following subgroups: men; patients with satisfactory weight loss; those satisfied with the procedure; those free from comorbidity and gastrointestinal symptoms; employed; good oral status; and those not hospitalised or regularly followed up for non-bariatric reasons. In study 3: Patients operated with a primary GBP between January 2008 and December 2012 were identified in the Scandinavian Obesity Surgery Register (SOReg). Patients with HRQoL data available at both baseline and 5 years after surgery were included. The study sample comprised 6998 patients (21% men). Gender differences in change in HRQoL were minor. Younger patients showed greater improvements in physical health scales. In general linear regression model analyses, age and weight loss correlated significantly with improvement in HRQoL after 5 years. Patients treated medically for depression preoperatively (13%) experienced less improvement in HRQoL than patients without such treatment. Patients with a postoperative complications (26%) had significantly less improvement in all aspects of HRQoL compared to those without any form of postoperative complication.This study confirmed the importance of weight loss for improvement in HRQoL after bariatric surgery. Preoperative medication for depression and suffering a complication during the five-year follow-up period were associated with less improvement in HRQoL. Studies 2 and 4: Included patients operated with laparoscopic gastric bypass at the department of surgery at the Örebro University Hospital between January 2004 and December 2005. Thirty-two females were prospectively recruited for this longitudinal study. In both studies, the following were measured at baseline, 2, 5 and 10 years postoperatively: bone mineral density (BMD); weight; height; S-calcium; S-albumin; S-creatinine; S-25(OH)-vitamin D; and fP-PTH. In study 4: Nine of the patients declined follow-up. BMD showed a statistically significant decline over the study period. The fall in BMD of the spine and femoral neck between baseline and 5 years after surgery was 19% and 25%,respectively. During the next five years period BMD continued to decline but at a lower rate. At 5 years 58 % had elevated PTH, this number declined at the next 5 years

A novel acoustic indoor localization system employing CDMA

Nowadays outdoor location systems have been used extensively in all fields of human life from military applications to daily life. However, these systems cannot operate in indoor applications. Hence, this paper considers a novel indoor location system that aims to locate an object within an accuracy of about 2 cm using ordinary and inexpensive off-the-shelf devices and that was designed and tested in an office room to evaluate its performance. In order to compute the distance between the transducers (speakers) and object to be localized (microphone), time-of-arrival measurements of acoustic signals consisting of Binary Phase Shift Keying modulated Gold sequences are performed. This DS-CDMA scheme assures accurate distance measurements and provides immunity to noise and interference. Two methods have been proposed for location estimation. The first method takes the average of four location estimates obtained by trilateration technique. In the second method, only a single robust position estimate is obtained using three distances while the least reliable fourth distance measurement is not taken into account. The system's performance is evaluated at positions from two height levels using system parameters determined by preliminary experiments. The precision distributions in the work area and the precision versus accuracy plots depict the system performance. The proposed system provides location estimates of better than 2 cm accuracy with 99% precision