Search results for: cancer patients

Authors: Catarina Grande, Barbara Mota

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The main goal of the present study was to understand the impact of childhood cancer on the quality of life of survivors and the extent to which oncologic disease affects the functionality and participation of survivors at the present time, compared to the time of diagnosis. Six survivors of pediatric cancer participated in the study. Participants were interviewed using a semi-structured interview, adapted from two instruments present in the literature - QALY and QLACS - and piloted through a previous study. This study is based on a qualitative approach using content analysis, allowing the identification of categories and subcategories. Subsequently, the correspondence between the units of meaning and the codes in the International Classification of Functioning, Disability, and Health for Children and Young, which contributed to a more detailed analysis of the impact on the quality of life of survivors in relation to the domains under study. The results showed significant changes between the moment of diagnosis and the present moment, concretely at the microsystem of the survivor. Regarding functionality and participation, the results show that the functions of the body are the most affected domain, emphasizing the emotional component that currently has a greater impact on the quality of life of survivors. The present study allowed identifying a set of codes for the development of a CIF-CJ core set for pediatric cancer survivors. He also indicated the need for future studies to validate and deepen these issues.

Keywords: cancer, participation, quality of life, survivor

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Authors: Benghezel Hichem

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Thyroid dysfunction in hemodialysis subjects is represented mainly by hypothyroidism. The objective of our work is to determine the thyroid profile of our hemodialysis patients and to highlight the prevalence of different thyroid disorders. Methods: This is a retrospective study performed on a mono centric 2 months (February and March 2013) on 42 hemodialysis patients (11 male and 31 female). We made the dosage of thyroid hormones Thyrotropin (TSH) ((free thyroxin ) FT4 and free Triodothyronin ) FT3) by chemiluminescence immunoassay method on cobas 6000 Roche Diagnostics. The results: The prevalence of biological hypothyroidism was 18% (7% with a high TSH isolated and a mean +/- SD 9.44 +/- 6.29, 5% with high TSH, and with low FT4 a mean +/- SD is 8.18 +/- 0.53 for TSH and 9.69 +/- 0.22 for FT4, One patient with a high TSH, and low FT4, FT3. 4% of patients with a low T3 syndrome with a mean +/- SD of 3.93 +/- 0,3 for FT3), we notice that 5% of patients with hyperthyroidism TSH collapsed and mean +/- SD of TSH is 0.017 +/- 0,001. Conclusion: The biological Hypothyroidism is a common endocrine disorder in chronic hemodialysis.

Keywords: hypothyroidism, hemodialysis, thyréostimulin, free thyroxin, triodothyronin

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Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein

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The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.

Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage

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Authors: A. Kamel Abd Elaziz Mohamed, B. Sameh Kamal el Maraghi

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Introduction: Adaptive support ventilation (ASV) is an improved closed-loop ventilation mode that provides both pressure-controlled ventilation and PSV according to the patient’s needs. Aim of the work: To compare the short-term effects of Adaptive support ventilation (ASV), with conventional Pressure support ventilation (PSV) in weaning of intubated COPD patients. Patients and methods: Fifty patients admitted in the intensive care with acute exacerbation of COPD and needing intubation were included in the study. All patients were initially ventilated with control/assist control mode, in a stepwise manner and were receiving standard medical therapy. Patients were randomized into two groups to receive either ASV or PSV. Results: Out of fifty patients included in the study forty one patients in both studied groups were weaned successfully according to their ABG data and weaning indices. APACHE II score showed no significant difference in both groups. There were statistically significant differences between the groups in term of, duration of mechanical ventilation, weaning hours and length of ICU stay being shorter in (group 1) weaned by ASV. Re-intubation and mortality rate were higher in (group 11) weaned by conventional PSV, however the differences were not significant. Conclusion: ASV can provide automated weaning and achieve shorter weaning time for COPD patients hence leading to reduction in the total duration of MV, length of stay, and hospital costs.

Keywords: COPD patients, ASV, PSV, mechanical ventilation (MV)

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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Authors: Kim Rod

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People whose chronic pain limits their independence are especially likely to become anxious and depressed. Mindfulness training has shown promise for stress-related disorders. Methods: Chronic pain patients who complained of anxiety and depression and who scored higher than moderate in Hamilton Depression Rating Scale (HDRS) and Hospital Anxiety and Depression Scale (HADS) as well as moderate in Quality of Life Scale (QOLS) were observed for eight weeks, three days a week for an hour of Mindfulness Meditation training with an hour daily home Mindfulness Meditation practice. Pain was evaluated on study entry and completion, and patients were given the Patients’ Global Impression of Change (PGIC) to score at the end of the training program. Results: Forty-seven patients (47) completed the Mindfulness Meditation Training program. Over the year-long observation, patients demonstrated noticeable improvement in depression, anxiety, pain, and global impression of change. Conclusion: Chronic pain patients who suffer with anxiety and depression may benefit from incorporating Mindfulness Meditation into their treatment plans.

Keywords: mindfulness, meditation, depression, anxiety, chronic pain

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Rahul Magazine, Shobitha Rao

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The aim of this study was to study the prescribing pattern of drugs in patients with ARDS (Acute Respiratory Distress Syndrome) managed at a tertiary care hospital. This observational study was conducted at Kasturba Hospital, Karnataka, India. Data of patients admitted from January 2010 to December 2012 was collected. A total of 150 patients of ARDS were included. Data included patients’ age, gender, clinical disorders precipitating ARDS, and prescribing pattern of drugs. The mean age of the study population was 42.92±13.91 years. 48% of patients were less than 40 years of age. Infection was the cause of ARDS in 81.3% of subjects. Antibiotics were prescribed in all the subjects and beta-lactams were prescribed in 97.3%. 41.3% were prescribed corticosteroids, 39.3% diuretics and 89.3% intravenous fluids. Infection was the commonest etiology for ARDS, and beta-lactams were the commonest antibiotics prescribed. Corticosteroids and diuretics were prescribed in a significant number of patients. Most of the patients received intravenous fluids.

Keywords: acute respiratory syndrome, beta lactams, corticosteroids, Acute Respiratory Distress Syndrome (ARDS)

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Authors: L. Szymanski, S. Wiak, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

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There exist more than one hundred different types of cancer, and therefore no particular treatment is offered to people struggling with this disease. The character of treatment proposed to a patient will depend on a variety of factors such as type of the cancer diagnosed, advancement of the disease, its location in the body, as well as personal preferences of a patient. None of the commonly known methods of cancer-fighting is recognised as a perfect cure, however great advances in this field have been made over last few decades. Once a patient is diagnosed with cancer, he is in need of medical care and professional treatment for upcoming months, and in most cases even for years. Among the principal modes of treatment offered by medical centres, one can find radiotherapy, chemotherapy, and surgery. All of them can be applied separately or in combination, and the relative contribution of each is usually determined by medical specialist in agreement with a patient. In addition to the conventional treatment option, every day more complementary and alternative therapies are integrated into mainstream care. There is one promising cancer modality - hyperthermia therapy which is based on exposing body tissues to high temperatures. This treatment is still being investigated and is not widely available in hospitals and oncological centres. There are two kinds of hyperthermia therapies with direct and indirect heating. The first is not commonly used due to low efficiency and invasiveness, while the second is deeply investigated and a variety of methods have been developed, including ultrasounds, infrared sauna, induction heating and magnetic hyperthermia. The aim of this work was to examine possibilities of heating magnetic nanoparticles under the influence of electromagnetic field for cancer treatment. For this purpose, multiwalled carbon nanotubes used as nanocarriers for iron particles were investigated for its heating properties. The samples were subjected to an alternating electromagnetic field with frequency range between 110-619 kHz. Moreover, samples with various concentrations of carbon nanotubes were examined. The lowest frequency of 110 kHz and sample containing 10 wt% of carbon nanotubes occurred to influence the most effective heating process. Description of hyperthermia therapy aiming at enhancing currently available cancer treatment was also presented in this paper. Most widely applied conventional cancer modalities such as radiation or chemotherapy were also described. Methods for overcoming the most common obstacles in conventional cancer modalities, such as invasiveness and lack of selectivity, has been presented in magnetic hyperthermia characteristics, which explained the increasing interest of the treatment.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, ligands

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Authors: Chuan Yin

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Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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Authors: Fahmi Hassan, Noorizan Abdul Aziz, Yahaya Hassan, Hazlinda Abu Hassan

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Sepsis incidence in critical care settings is a major problem in health care. Extended antibiotic infusion is thought to be superior to traditional dosing especially when treating critically ill patients with sepsis. We compared clinical outcomes of critically ill patients with sepsis receiving 30-minute meropenem infusion and three-hour meropenem infusion. A retrospective case-control study was conducted among septic patients treated with meropenem infusion in ICUs of three hospitals. Patients included in the study received either extended or standard meropenem infusion as per the practice of individual settings. Outcomes and clinical data were retrospectively collected from the electronic databases and patients’ files. A total of 108 patients received extended meropenem infusion while another 117 patients received standard meropenem infusion. Patients receiving the extended meropenem infusion were found to have a significantly lower shorter length of hospital and ICU stay. It was also found that among those receiving extended meropenem infusion, 54.7% (64/117) had a reduction of SAPS II score, while only 44% (48/108) of patients receiving standard meropenem infusion had reduced scores. This study will strengthen the evidence in using extended meropenem infusion as a standard practice in critical care settings. As this is the first study of its kind done in Malaysia, it proves that prolonged meropenem infusion may be beneficial to critically ill patients with sepsis. However, randomized clinical trials with large sample size should be carried out in local settings in order to minimize other confounders that may influence with the result of the study.

Keywords: antibiotics, beta lactams, critical care, extended infusion, meropenem

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Dara Kutsyk, Olga Bondarenko, Mariya Sorochka

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In 21-century type 2 diabetes (T2D) has become a global health and social problem in the whole world. The goal of treatment for patients with T2D is to prevent complications of diabetes - macrovascular diseases (heart disease, stroke, and peripheral vascular disease) and microvascular diseases (retinopathy, neuropathy and nephropathy). Nitric oxide (NO) plays an important role in maintaining vascular homeostasis. Loss of NO function is one of the earliest indicators of disease and its progression especially in patients with T2D. Aim: To compare NO level between patients with well and bad controlled glycemia in T2D. Methods: The study included 32 patients with T2D. The diagnosis of T2D was confirmed due to International Diabetes Federation (IDF) criteria 2015. Patients were divided into two groups: with well controlled glycaemia (HbA1c < 7%) and bad controlled glycaemia (HbA1c > 7%). The control group consists of 15 healthy subjects. Results: NO level in patients with T2D is significantly higher (27,2 ±3,1 µmol), compared to controls (18,86±0,9 µmol; p < 0,001). A significant difference in NO level was found between patients with bad controlled glycaemia (25,9±2,2 µmol) and well controlled glycaemia (28,7 ± 3,0 µmol; p<0,01). The study showed a moderate negative correlation between NO level and HbA1c (-0,399; р< 0,05). Conclusions: Production of NO is impaired in patients with T2D, especially with badly controlled glycaemia. With the increase in HbAc serum NO decreases. This can be the main target for prevention vascular complication in T2D.

Keywords: type 2 diabetes, glycated hemoglobin, nitric oxide, Diabetes mellitus

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Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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Authors: Faizan Rathore, Naveed Sultan, Humphrey O. Connor

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This study was carried out from Jan '12-Dec'12 to assess current practice in Kerry General Hospital against the age-related indicators for colonoscopies. A total of 1474 colonoscopies were performed,1177(79.9%) were diagnostic and 297 (20.1%) were therapeutic, patients were divided into 4 age groups under 75, 75-80, 81-85, 86+. The trend analysis revealed an increase in diagnostic colonoscopies and decrease in therapeutic colonoscopies with age. 664(45.04%) of colonoscopies were reported normal which made up the majority of the total diagnoses, 1330 (90.2%) of colonoscopies occurred without any complications. Main complications were patient discomfort being the highest, present in 112(7.6%) of patients, and lowest being urticaria around the IV site present in 1 (0.1%) of the cases. Patient discomfort was higher in younger patients as evidenced by 98 cases aged <75 , followed by 11 cases aged 75-80, 2 cases aged 81-85 and 1 case aged >86. Highest percentage of poor tolerance was found in 14 (1.1%) of total patients <75, 1 (0.8%) of total patients aged 75-80, 1(1.7%) of total patients in age group 81-85 and none (0%) in age group >86. We have established the safety of colonoscopy, low rate of complications and a better tolerance in the elderly from this study, however, its utility, especially in the presence of other comorbidities in elderly is questionable.

Keywords: colonoscopy, elderly patients, utility, tolerance

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Authors: Arfan Ali Nagra, Tariq Shahzad, Meshal Alharbi, Khalid Masood Khan, Muhammad Mugees Asif, Taher M. Ghazal, Khmaies Ouahada

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Gene selection is an essential step for the classification of microarray cancer data. Gene expression cancer data (DNA microarray) facilitates computing the robust and concurrent expression of various genes. Particle swarm optimization (PSO) requires simple operators and less number of parameters for tuning the model in gene selection. The selection of a prognostic gene with small redundancy is a great challenge for the researcher as there are a few complications in PSO based selection method. In this research, a new variant of PSO (Self-inertia weight adaptive PSO) has been proposed. In the proposed algorithm, SIW-APSO-ELM is explored to achieve gene selection prediction accuracies. This new algorithm balances the exploration capabilities of the improved inertia weight adaptive particle swarm optimization and the exploitation. The self-inertia weight adaptive particle swarm optimization (SIW-APSO) is used to search the solution. The SIW-APSO is updated with an evolutionary process in such a way that each particle iteratively improves its velocities and positions. The extreme learning machine (ELM) has been designed for the selection procedure. The proposed method has been to identify a number of genes in the cancer dataset. The classification algorithm contains ELM, K- centroid nearest neighbor (KCNN), and support vector machine (SVM) to attain high forecast accuracy as compared to the start-of-the-art methods on microarray cancer datasets that show the effectiveness of the proposed method.

Keywords: microarray cancer, improved PSO, ELM, SVM, evolutionary algorithms

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin J. T. Reaney

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Flaxseed (Linum usitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. The flax plant synthesizes an array of biologically active cyclic peptides or linusorbs (LOs, a.k.a. cyclolinopeptides) from three or more ribosome-derived precursors. [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in human epithelial cancer cell line (Calu-3) cells, and inhibit T-cell proliferation, but the mechanism of LOs action is unknown. Using gene expression analysis in nematode cultures and human cancer cell lines, we have observed that LOs exert their activity, in part, through induction of apoptosis. Specific LOs’ properties include: 1) distribution throughout the body after flaxseed consumption; 2) induce heat shock protein (HSP) 70A production as an indicator of stress and address the issue in Caenorhabditis elegans (exposure of nematode cultures to [1–9-NαC]-linusorb B3 induced a 30% increase in production of the HSP 70A protein); 3) induce apoptosis in Calu-3 cells; and 4) modulate regulatory genes in microarray analysis. These diverse activities indicate that LOs might induce apoptosis in cancer cells or act as versatile platforms to deliver a variety of biologically active molecules for cancer therapy.

Keywords: flaxseed, linusorb, cyclic peptide, orbitides, heat shock protein, apoptosis, anti-cancer

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Authors: Tarek K. Jalouta, Jolietta R. Holliman, Kathryn R. Burke, Kathleen M. Bewley-Thomas

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Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. In the United States, HCV screening awareness, treatment, and linkage to care are under continues ascending progress. However, still millions of people are asymptomatically infected and undiagnosed yet. Through this community mission, we sought to identify the best and the newest strategies to identify those infected people to educate them, link them to care and cure them. Methods: We have identified patients that did not have a prior HCV screening in our Electronic medical record (EMR) including all our different hospital locations (South Suburban Chicago, Northern, Western and Central Indiana). Providing education to all Primary care/Gastroenterology/Infectious diseases providers and staff in the clinic to increase awareness of the HCV screening. Health-related quality of life, chronic clinical complications, and demographics data were collected for each patient. All outcomes of HCV antibody-reactive and HCV RNA–positive results were identified and statistically analyzed. Results: From July 2016 to July 2018 we screened 35,720 individuals of birth cohort in our different Franciscan’s health medical centers. Of the screened population, 986 (2.7%) individuals were HCV AB-reactive. Of those, 319 (1%) patients were HCV RNA-positive, and 264 patients were counseled and linked to providers. 34 patients initiated anti-HCV therapy with successful treatment. Conclusions: Our HCV screening augmentation project considered the largest screening program in the Midwest. Augmenting the HCV screening process through creating a Best Practice Alert (BPA) in the EMR (Epic Sys.) and point of care testing could be helpful. Although continued work is required, our team is working on increase screening through adding HCV test to CBC-Panels in Emergency Department settings, phone calls to all birth cohort individuals through Robo-Calling System aimed to reach 75,000 individuals by 2019. However, a better linkage to care and referral monitoring system to all HCV RNA positive patients is still needed, and access to therapy, especially for uninsured patients, is challenging.

Keywords: chronic hepatitis C, chronic hepatitis C treatment, chronic hepatitis C screening, chronic hepatitis C prevention, liver cancer

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Authors: Ibtisam Al-Zaru

Abstract:

Background: Worldwide, depression among coronary artery disease (CAD) patients is considered a serious problem that may cause many complications and negative consequences; particularly serious being increased mortality and morbidity rate. Studying depression among CAD patients in Jordan has not been investigated thoroughly and thus a need for further studies has been a priority. Aims: To assess depression in non-hospitalized Jordanian patients with CAD; to describe the relationship between socio-demographic data, health related factors, and depression; and to examine the best predictors of depression in non-hospitalized Jordanian patients with CAD. Method: A cross-sectional-descriptive design was used to collect data from 174 non-hospitalized Jordanian patients diagnosed with CAD in outpatients’ cardiac clinics, using a self- administered questionnaires and Cardiac Depression Scale. Results: 53.4% of CAD patients reported mild/moderate, and severe depressive symptoms. Significant relationships between depressive symptoms and some demo-clinical characteristics (i.e. being female gender; having of chronic disease and surgical history; being physically inactive, and perceived their sexual activity, physical and psychological as poor). The preceding factors are also found to be statistically significant predictors for depression among this patients’ group. Conclusion: Jordanian patients with CAD had various levels of severity regarding their depressive symptoms. Therefore, health care providers need to introduce depression assessment and treatment in cardiac rehabilitation to control depression and its impact on the patient. Consequently, such control will reduce co-morbidity, mortality, complications and health costs among CAD patients and enhance the quality of their lives.

Keywords: coronary artery disease, predictors, depression, prevalence

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Authors: Kave Moloudi, Heidi Abrahamse, Blassan P. George

Abstract:

Radiotherapy (RT) and photodynamic therapy (PDT) are both forms of cancer treatment that aim to kill cancer cells while minimizing damage to healthy tissue. The similarity between RT and PDT lies in their mechanism of action. Both treatments use energy to damage cancer cells. RT uses high-energy radiation to damage the DNA of cancer cells, while PDT uses light energy to activate a photosensitizing agent, which produces reactive oxygen species (ROS) that damage the cancer cells. Both treatments require careful planning and monitoring to ensure the correct dose is delivered to the tumor while minimizing damage to surrounding healthy tissue. They are also often used in combination with other treatments, such as surgery or chemotherapy, to improve overall outcomes. However, there are also significant differences between RT and PDT. For example, RT is a non-invasive treatment that can be delivered externally or internally, while PDT requires the injection of a photosensitizing agent and the use of a specialized light source to activate it. Additionally, the side effects and risks associated with each treatment can vary. In this review, we focus on generalizing the 6Rs of radiobiology in PDT, which can open a window for the clinical application of Radio-photodynamic therapy with minimum side effects. Furthermore, this review can open new insight to work on and design new radio-photosensitizer agents in Radio-photodynamic therapy.

Keywords: radiobiology, photodynamic therapy, radiotherapy, 6Rs in radiobiology, ROS, DNA damages, cellular and molecular mechanism, clinical application.

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Authors: Hateem Zafar Kayani, Nageen Hussain

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The main aim is to analyze the mutations of DNASE I gene in diabetic patients. A total of 120 diabetes patients and 120 controls were sampled. The total number of male diabetic patients included in the study was 79 (66%) while female patients were 41 (34%) in number. Exon 8 of the DNASE I gene was amplified by using thermo cycler. The possible band of interest was located at 165 base pairs. Two samples showed similar missense mutations at 127th position of exon 8 which replaced amino acid Arginine (Arg) to Glutamine (Gln). All controls showed no mutations. The association of diabetes with different levels of blood pressure and body mass index (BMI) were found to be significant.

Keywords: deoxyribonuclease I, polymerase chain reaction, insulin-dependent diabetes mellitus, non-insulin dependent diabetes mellitus

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

Abstract:

Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

Abstract:

Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

Abstract:

Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: Omonov Jahongir Mahmatkulovic

Abstract:

Purpose: To study the significance of D-dimer (DD), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen coagulation parameters (Fg) in predicting the course, severity and prognosis of COVID-19. Source and method of research: From September 15, 2021, to November 5, 2021, 93 patients aged 25 to 60 with suspected COVID-19, who are under inpatient treatment at the multidisciplinary clinic of the Tashkent Medical Academy, were retrospectively examined. DD, PT, APTT, and Fg were studied in dynamics and studied changes. Results: Coagulation disorders occurred in the early stages of COVID-19 infection with an increase in DD in 54 (58%) patients and an increase in Fg in 93 (100%) patients. DD and Fg levels are associated with the clinical classification. Of the 33 patients who died, 21 had an increase in DD in the first laboratory study, 27 had an increase in DD in the second and third laboratory studies, and 15 had an increase in PT in the third test. The results of the ROC analysis of mortality showed that the AUC DD was three times 0.721, 0.801, and 0.844, respectively; PT was 0.703, 0.845, and 0.972. (P<0:01). Conclusion”: Coagulation dysfunction is more common in patients with severe and critical conditions. DD and PT can be used as important predictors of mortality from COVID-19.

Keywords: Covid19, DD, PT, Coagulogram analysis, APTT

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Authors: Neda Valizadeh, Mani Mofidi, Sama Haghighi, Ali Hashemaghaee, Soudabeh Shafiee Ardestani

Abstract:

Background: There are many systems and parameters to evaluate trauma patients in the emergency department. Most of these evaluations are to distinguish patients with worse conditions so that the care systems have a better prediction of condition for a better care-giving. The purpose of this study is to determine the relationship between axillary body temperature and mortality in patients hospitalized in the intensive care unit (ICU) with multiple traumas and with other clinical and para-clinical factors. Methods: All patients between 16 and 75 years old with multiple traumas who were admitted into Emergency Department then hospitalized in the ICU were included in our study. An axillary temperature in the first and the second day of admission, Glasgow cola scale (GCS), systolic blood pressure, Serum glucose levels, and white blood cell counts of all patients at the admission day were recorded and their relationship with mortality were analyzed by SPSS software with suitable statistical tests. Results: Axillary body temperatures in the first and second day were statistically lower in expired traumatic patients (p=0.001 and p<0,001 respectively). Patients with lower GCS had a significantly lower first-day temperature and a significantly higher mortality. (p=0.006 and p=0.006 respectively). Furthermore, the first-day axillary temperature was significantly lower in patients with a lower first-day systolic blood pressure (p=0.014). Conclusion: Our results showed that lower axillary body temperature in the first day is associated with higher mortality, lower GCS, and lower systolic blood pressure. Thus, this could be used as a predictor of mortality in evaluation of traumatic patients in emergency settings.

Keywords: fever, trauma, mortality, emergency

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Authors: Haile F. Darge, Hsieh C. Tsai

Abstract:

The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Fateme Hadadian, Behnam Khaledi Paveh, Hosein Feizi

Abstract:

Background: High number of patients with end-stage renal disease worldwide, and Iran and the patients required hemodialysis, As well as symptoms and treatment process and its impact on quality of life The researcher had to take a step towards solving these problems. Methods: In randomized clinical trial in 60 hemodialysis patients admitted to hospital hemodialysis Imam Reza (AS) were studied. Using questionnaires dialysis patients' QOL, quality of life was measured in patients and controls were divided randomly into two groups. Benson's relaxation method for the experimental group and two months at home, once per day, respectively and the control group received no special action. Immediately after the end of the period with was used for evaluating the quality of life in both the experimental and control groups were survey and data using independent t-test were used for statistical analysis. Results: The general dimensions of quality of life scores before and after intervention, there was significant difference (P=0/001). But this difference was not significant after QOL (P=0/2). Between QOL scores before and after treatment between the two groups was statistically significant (P=0/02). Conclusion: Benson relaxation has the desired effect on quality of life in hemodialysis patients and can be used as a useful method to enhance the quality of life in hemodialysis patients, implementation and training will be given.

Keywords: hemodialysis, quality of life, Benson muscle relaxation, biomedicine

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