Time-Resolved Femtosecond Laser Spectroscopic Study of the Reaction

Being currently the second and potentially becoming the first cause of death in North America, cancer has been the focus of researchers from various areas of science. Chemotherapy is one of the leading treatment options for treating various types of cancer, particularly advanced cancers. Among different chemotherapeutic drugs currently used against cancer, cisplatin (CDDP) is considered as one of the most effective and widely used. Despite being the most successful drug in cancer chemotherapy, cisplatin has some shortcomings that restrict it from being more widely used. More than three decades of intensive research has not yet clearly explained why these shortcomings are associated with cisplatin treatment. Using the advanced “Pump-Probe Femtosecond Time-Resolved Transient Absorption Laser Spectroscopy” technique to study the reaction dynamics of cisplatin at the molecular level, we discovered new findings that make a profound contribution to our understanding of the mechanism of activity of CDDP as a very widely used and effective anticancer drug. By observing the reaction dynamics of cisplatin both in its reaction with electrons in water, and with all four DNA bases, in real time, we shed new light on the issues that have long been elusive for the last three decades. In addition to these two main research goals, we utilized the same methodology to examine the reaction dynamics of transplatin, which currently is not a clinically effective drug, despite being an isomer of cisplatin. In this part we mainly focused on examining the molecular reaction dynamics of transplatin photoactivation caused by UV irradiation. Here, we studied the transplatin reaction with electrons in water as well as with four DNA bases. Results obtained in this thesis work clearly reveal the mechanism underlying the cytotoxicity enhancement of this molecule after it is irradiated by UV radiation. The data obtained by our experiments provide a mechanistic understanding of this cytotoxicity enhancement at the molecular level. As the last goal in our research, we compared the explored reaction dynamics of cisplatin with its clinically ineffective trans isomer, transplatin. We believe that our understanding of one of these isomers, would also contribute to understanding of the other. The methodology we used to examine transplatin was the same as what we used for cisplatin. First, we monitored the possible reactions of transplatin with prehydrated electrons in water. After this, the dynamics of transplatin’s reactions with DNA bases were examined. For the first time, we directly observed the reactions of cisplatin and discovered that its extremely high reactivity with prehydrated electrons happens in an ultrafast process. We also showed the order of reactivity of all four DNA bases with cisplatin and transplatin to be G > A > C > T. Finally, in comparing cis and trans isomers of DDP, we discovered cisplatin to be about 50% more reactive, suggesting why it is much more cytotoxic. In all of these investigations we obtained promising results that revolutionize our understanding of the mechanism of action of cisplatin as a very important drug in current cancer chemotherapy

Measurement of superficial and deep abdominal muscle thickness: an ultrasonography study

BACKGROUND: Real-time ultrasound imaging is a valid method in the field of rehabilitation. The ultrasound imaging allows direct visualization for real-time study of the muscles as they contract over the time. Measuring of the size of each abdominal muscle in relation to the others provides useful information about the differences in structure, as well as data on trunk muscle activation patterns. The purpose of this study was to assess the size and symmetry of the abdominal muscles at rest in healthy adults and to provide a reference range of absolute abdominal muscle size in a relatively large population. METHOD: A total 156 healthy subjects with the age range of 18–44 years were randomly recruited. The thickness of internal oblique, external oblique, transverse abdominis, and rectus abdominis muscles was measured at rest on both right and left sides using ultrasound. Independent t test was used to compare the mean thickness of each abdominal muscle between males and females. Differences on side-to-side thicknesses were assessed using paired t test. The association between abdominal muscle thicknesses with gender and anthropometric variables was examined using the Pearson correlation coefficient. RESULTS: A normal pattern of increasing order of mean abdominal muscle thickness was found in both genders at both right and left sides: transverse abdominis < external oblique < internal oblique < rectus abdominis. There was a significant difference on the size of transverse abdominis, internal oblique, and external oblique muscles between right and left sides in both genders. Males had significantly thicker abdominal muscles than females. Age was significantly correlated with the thickness of internal oblique, external oblique, and rectus abdominis muscles. Body mass index was also positively correlated with muscle thickness of rectus abdominis and external oblique. CONCLUSIONS: The results provide a normal reference range for the abdominal muscles in healthy subjects and may be used as an index to find out abnormalities and also to evaluate the effectiveness of different interventions

Impact of Rifampin Induction on the Fermentation Production of Ganoderic Acids by Medicinal Mushroom Ganoderma lucidum

Backgrounds and Objectives: Ganoderic acids are the most valuable secondary metabolites in Ganoderma lucidum traditional medicinal mushrooms, which have shown antitumor properties in many studies. However, application of ganoderic acids is limited due to low yield production. Recently, it was shown that static liquid culture could be a proven technology for producing ganoderic acids in Ganoderma lucidum, and that applying elicitors could be a potential strategy to improve their production. Materials and Methods: In this work, the effect of rifampin, a cyto-chromes P450 inducer, on production of ganoderic acids was studied, and Response Surface Methodology was applied to optimize the elicitor induction. Then total ganoderic acid in the harvested mycelia was extracted and its absorbency was measured. Results and Conclusion: The results showed an increase in the concen-tration of ganoderic acid in all samples. Moreover, optimum concentration and induction time of rifampin were obtained. The proposed model predicted the maximum ganoderic acid production as 18.6 mg g-1 in which the optimal concentration and time induction obtained were 100 μM and day 9, respectively. This work demonstrated a useful method for the enhanced production of ganoderic acids by Ganoderma lucidum.

Living in the Blurry World: The Story of HIV-infected Iranian Nurses

Background: Despite progress in reducing HIV-related mortality over the past decade, the prevalence and incidence of HIV infection slightly decreased. Nursing profession as a part of the health care system is most affected by HIV/AIDS. HIV-positive nurses need more support from governments and officials. Little is known about how Iranian HIV-positive nurses experience their life situations.  Aim: This study evaluated the experiences of HIV-positive nurses and their attempts to manage HIV/AIDS in personal and occupational livings. Method: The hermeneutic phenomenological approach developed by van Manen's methodology (1990) was adopted to explore the experience of daily life for HIV-positive nurses. A purposive sampling of eight HIV-positive nurses was recruited. Face-to-face in-depth interviews were conducted with two female and six male nurses who had infected with HIV via occupational exposure. Data were analyzed using thematic analysis. Results: The experiences of HIV-infected nurses derived in one major theme and three subthemes. Major theme “living in the blurry world” extracted from three sub-themes: ‘being-in-the-risky world’, ‘being-in-the-shadow of illness’, and ‘ambiguous being-in-the-world’. Implications for Practice: HIV positive nurses perceive the world full of fear and ambiguities. They prefer to suffer in silence and reluctant to disclose their seropositive status. The results of this study can be used by professionals to better understand the HIV positive nurses' world and make more efforts to improve their workplace experiences and reduce stigma in the future

Nanohydroxyapatite Silicate-Based Cement Improves the Primary Stability of Dental Implants: An In Vitro Study

Objectives. Insufficient cortical bone volume when placing implants can lead to lack of primary stability. The use of cement as a bone fill material in bone defects around dental implant could result in better clinical outcome. HA has shown excellent biological properties in implant dentistry. The purpose of this study was to evaluate the effect of nanohydroxyapatite powder (Nano-HA) in combination with accelerated Portland cement (APC) on implant primary stability in surgically created circumferential bone defects in a bovine rib in vitro model. Materials and Methods. Sixteen bovine rib bones and thirty-six implants of same type and size (4 mm × 10 mm) were used. Implants were divided into six groups: no circumferential bone defect, defect and no grafting, bone chips grafting, Nano-HA grafting, APC grafting, and Nano-HA mixed to APC grafting (Nano-HA-APC). Circumferential defects around the implants were prepared. The implant stability quotient (ISQ) values were measured before and after the grafting. Results. APC exhibited the highest ISQ values. A significant increase of ISQ values following the grafting of Nano-HA-APC (18.08±5.82) and APC alone (9.50±4.12) was achieved. Increase of ISQ values after 72 hours was 24.16±5.01 and 17.58±4.89, respectively. Nano-HA grafting alone exhibited the least rise in ISQ values. Conclusions. Nanohydroxyapatite silicate-based cement could improve the primary stability of dental implants in circumferential bone defect around implants

Evaluation of the Task Compliance of Medical Education Development Centers from the Viewpoint of the Managers of the Centers

Background: Medical education development (MED) centers are established in order to improve the quality of medical education. It seems that after more than two decades since the establishment, the centers still have difficulties to perform some tasks. Objectives: According to the important role of MED centers, the current study aimed at adapting the performances of such centers with their assigned tasks. Methods: The current qualitative applied study was conducted in 2013. The statistical population of the study included managers of MED centers in Iran. Data were collected through a questionnaire containing open questions. During a national meeting the questionnaire distributed among 40 managers of MED centers and then analyzed using content analysis. Results: More than half of the major functions that the managers stated, were referred to the first, second, and fourth tasks of the centers, and only 18% of the major functions were related to other tasks (11 cases). About 28% of the functions performed in such centers had no direct correlation with any of the 14 tasks. Conclusions: Despite the history of MED centers for several decades, they are not justified in respect to their duties. It is recommended that guidelines be developed to address all duties and adequately monitor their implementation. Keywords Medical Education Development Centers Performance Indicator Quality Medical Education Ira

Childhood cardiovascular risk factors, a predictor of late adolescent overweight

Background: We conducted a prospective study to elucidate the effects of increased cardiovascular risk factors on future weight gain and also the relation between body mass index (BMI) and other cardiovascular risk factors in children and adolescents. Materials and Methods: This study was conducted on 1525 nonobese children and adolescents with an age range of 3-16 years old, participating in the 1st phase and follow-up phases of Tehran Lipid and Glucose Study. The subjects were evaluated 4 times with a 3-year time interval regarding lipid profile status and BMI, and other cardiovascular disease (CVD) risk factors. All the cases had a BMI <85% and had been appraised in at least two evaluation points. Results: Cardiovascular risk factors, high-density lipoprotein (HDL) (P = 0.019), low-density lipoprotein (P = 0.016), triglyceride (TG) (P < 0.001), and blood pressure (BP) (P = 0.001); had significant effects on weight gain. There was also no difference between boys and girls and no age trend for increasing weight in both groups. The associations between BMI with cardiovascular risk factors were assessed cross-sectionally. For both sexes, BMI was significantly correlated to systolic and diastolic BP and TG (P = 0.05). For girls, BMI was significantly related to HDL (P = 0.05) regardless to age, but in boys, the relation of BMI with HDL only increased with age (P = 0.05). Conclusion: Increased CVD risk factors are predictors of future overweight in childhood and adolescent and increased weight is linked significantly with dyslipidemia and hypertension in this age group

Characterizing magnetization exchange in healthy human brain and bovine brain

Multi component T₂ relaxation imaging is an established MRI technique for measuring myelin water (MW, water molecules trapped between myelin sheath bilayers). Myelin water fraction (MWF, the fraction of central nervous system water with a short T₂) has been quantitatively correlated to histological staining for myelin in central nervous system tissue and hence is considered an in vivo measure of myelin content. Various studies have reported on the measurement of MWF with a diverse range of neurological diseases such as Multiple Sclerosis (MS), Schizophrenia, epilepsy, and Phenylketonuria (PKU). Although T₂ relaxation is the main probe for measuring MWF, understanding longitudinal relaxation, T1, is essential in a number ways such as the following: 1) Estimation of the corrections for myelin water fraction that need to be taken into account due to water exchange processes in white matter in vivo is highly dependent on T₁ relaxation. 2) Investigating the effect of T1-weighting in MWF measurements at short TR. This is especially important due to recent breakthroughs in developing rapid 3-D whole brain approaches to MWF measurements that are pushing towards shorter and shorter TR times in order to make this technique a valuable clinical imaging tool. First, in vivo MRI data from multi-component T₂ relaxation from 57 healthy subjects collected at 3.0 T was analyzed to estimate the corrections which have to be taken into account due to magnetization exchange in white matter. These results showed that these MWF corrections were less than 15% and are uniform across various white matter structures. Next, the variation of MWF as function of repetition time (TR) was investigated using in vivo MRI data collected at 3.0 T from healthy subjects. These results clearly showed that the measured MWF increased as the TR decreased. Finally, in order to measure T₁ as well as the rate of magnetization exchange with higher precision, data from bovine brain white matter was collected using a 4.7 T NMR spectrometer. The results from this study clearly showed that the T₁ had two components; therefore magnetization in bovine white matter is not in a fast exchange regime on the T₁ timescale.Science, Faculty ofPhysics and Astronomy, Department ofGraduat